MONDO Publications

Carmine Zoccali, Giovanni Strippoli, Francesco Locatelli, Francesca Mallamaci, Len Usyat, Stefano Stuard

CONCLUSIONSFuture trials should be multicenter, phenotype-enriched, mechanism-specific, adequately powered, and endpoint-adjudicated. Endpoints should match the intervention: rhythm monitoring for potassium strategies, cardiac magnetic resonance and objective volume assessment for sodium or volume interventions, and integrated inflammatory, nutritional, vascular, and clinical outcomes for membrane-based approaches.AIMThis narrative review examines dialysis strategies intended to mitigate cardiovascular stress arising from cyclic volume loading, rapid ultrafiltration, electrolyte shifts, myocardial stunning, vascular stiffness, inflammation and anemia, middle-molecule toxicity, loss of residual kidney function, and the long interdialytic interval.EVIDENCE SYNTHESISRandomized trials and individual-patient-data meta-analyses have evaluated high-dose online hemodiafiltration, with some studies reporting improved survival compared with conventional hemodialysis. Results have varied across trials, and questions remain regarding treatment delivery, generalizability and the mechanisms underlying the observed effects. More frequent, nocturnal, and long-duration dialysis schedules improve intermediate endpoints, including left ventricular mass, blood pressure, phosphate control, ultrafiltration intensity, and treatment tolerance, but hard-outcome evidence remains limited. Expanded hemodialysis with medium cut-off membranes improves clearance of larger middle molecules, although cardiovascular benefit is unproven. Individualized dialysate potassium and sodium prescriptions are physiologically compelling precision-dialysis approaches targeting arrhythmia risk, volume overload, blood pressure, and cardiac remodeling, but definitive endpoint trials are needed. Incremental dialysis might preserve residual kidney function in selected incident patients, but cardiovascular benefit remains vulnerable to selection bias.BACKGROUNDCardiovascular disease remains the leading cause of death in patients receiving maintenance dialysis, whereas conventional thrice-weekly hemodialysis was developed primarily around small-solute clearance rather than cardiovascular protection.

Peter J Blankestijn, Sanne Roos, Claudia Barth, Michiel L Bots, Krister Cromm, Andrew Davenport, Jörgen Hegbrant, Giovanni Strippoli, Robin W M Vernooij, Bernard Canaud

Hemodiafiltration (HDF) with online production of substitution fluid has emerged as kidney replacement therapy and is increasingly adopted worldwide. Recent randomized controlled trials, individual participant data meta-analyses, and large real-world studies have demonstrated that high-volume HDF improves clinical outcomes compared with conventional high-flux hemodialysis (HD), including reduction in all-cause mortality and hospitalization. Importantly, these benefits appear dose-dependent, with achieved convective volume serving as a modifiable treatment target. Beyond survival, data suggest advantages in patient reported outcomes and evidence for cost-effectiveness. This review provides a practical overview of contemporary HDF delivery, focusing on the prescription variables that determine treatment performance, including vascular access, blood flow rate, filtration fraction, treatment time, dialyzer characteristics, and machine technology. Current evidence suggests that high-volume post-dilution HDF can be achieved safely and reproducibly in routine clinical practice using standard thrice-weekly treatment schedules and contemporary dialysis platforms. Monitoring should extend beyond conventional small-solute clearance metrics to include indicators of middle-molecule removal and patient-centered outcomes. Future developments are expected to move HDF from a uniform prescription strategy towards a more individualized approach. Emerging data support refinement of convection-volume targets according to patient characteristics and treatment response, while incorporation of patient-reported outcomes and predictive models may facilitate precision-based therapy. Advances in automation, digital monitoring, biosensors, and artificial intelligence are most likely to further optimize treatment delivery and personalization. Although implementation requires investment in infrastructure, training, and quality assurance, growing evidence suggests that these costs may be offset by improved clinical outcomes, reduced healthcare utilization, and enhanced sustainability. Collectively, current evidence supports high-volume HDF as among the most effective dialysis modality currently available and it is likely to become the global standard for kidney replacement therapy.

Audrey Yuki Brinker, Felix H Fischer, Giovanni F M Strippoli, Krister Cromm, Peter J Blankestijn, Michiel L Bots, Claudia Barth, Bernard Canaud, Andrew Davenport, Kathrin I Fischer, Jörgen Hegbrant, Marietta Török, Robin W M Vernooij, Mark Woodward, Matthias Rose, Gregor Liegl

RESULTSOf 1,360 included patients (37.1% women, mean age 62.4 years), 266 (19.6%) died during follow-up. All three PF measures demonstrated statistically significant and comparable associations with mortality in both unadjusted and adjusted analyses. Adjusted hazard ratios (HRs) per 1-point increase in PF score were 0.96 (95% CI, 0.95-0.98) for PROMIS-PF4a, 0.95 (95% CI, 0.94-0.97) for PPT, and 0.96 (95% CI, 0.94-0.97) for the composite score. Discriminative ability was modest but similar across measures (adjusted C-index ≈ 0.71). Across all assessment types, severe PF impairment (T-score<30), was associated with substantially higher mortality risk.RATIONALE & OBJECTIVEWhile physical function (PF) measures obtained through patient-reported outcomes (PRO) are simpler to obtain than performance-based outcomes (PerfO), their relative prognostic value remains unclear. This study compared the associations of these measures with all-cause mortality in patients with kidney failure enrolled in the CONVINCE trial.CONCLUSIONSPhysical function was strongly and independently associated with mortality in kidney failure. The patient-reported PROMIS-PF4a and the performance-based PPT demonstrated comparable associations with mortality. These findings support use of the brief PROMIS-PF instrument as a practical alternative to performance-based assessments for routine monitoring of PF in dialysis care.LIMITATIONSObservational cohort analysis of a trial population; generalizability is limited to trial participants and to the examined PF tools.STUDY DESIGNObservational multicenter cohort study.OUTCOMEAll-cause mortality over a median follow-up of 30 months.PREDICTORSBaseline PF scores derived from (1) PRO: the 4-item PROMIS-PF short form (PROMIS-PF4a), (2) PerfO: the Physical Performance Test (PPT), and (3) composite PF scores integrating both assessment types. The different PF metrics were standardized to permit comparisons on a common scale.ANALYTICAL APPROACHUnadjusted and multivariable Cox proportional hazards regression models fitted for each PF predictor. Model discrimination was evaluated using Harrell's C-index and time-dependent AUCs. Restricted cubic splines assessed risk across the PF continuum. Kaplan-Meier curves were stratified according to predefined PROMIS-PF score cut points.SETTING & PARTICIPANTSAdult patients with kidney failure undergoing high-dose hemodiafiltration or high-flux hemodialysis enrolled in the CONVINCE trial between November 2018 and April 2021.

Doris H Fuertinger, Felix J Meigel, Aiyuan Wang, Sabrina Casper, Sheng-Han Yueh, Kevin Ho

Background: Ultrafiltration (UF) during hemodialysis is typically prescribed as a fixed treatment goal and delivered using a largely constant ultrafiltration rate throughout the session. We evaluated whether Adaptive Ultrafiltration (Adaptive UF), a physiological closed-loop control strategy guided by continuous relative blood volume (RBV) monitoring, could improve RBV target attainment while individualizing fluid removal within predefined treatment constraints. Methods: We performed a paired patient-specific in silico study using 119,472 historical hemodialysis treatments from 11,246 U.S. patients. Treatment-specific plasma refill rate profiles were derived from recorded RBV and ultrafiltration data. For each historical treatment, a corresponding Adaptive UF treatment was simulated and compared with the corresponding originally delivered treatment. Outcomes included the percentage of time within a predefined favorable RBV target region, UF delivery, and operational performance. Results: Mean time within the RBV target region increased from 36.3% with historically delivered treatments to 56.4% with Adaptive UF, showing an absolute improvement of 20.2 percentage points (95% CI, 19.9-20.5); target attainment improved in 90.0% of patients. Mean area outside the target range decreased from 280.7 to 139.5 RBV %-minutes. Mean achieved UF volume increased by 296.4 mL, although treatment-level UF delivery was bidirectional, increasing in 83.1% and decreasing in 16.9% of treatments. UF rates remained below 13 mL/kg/h in all simulations, and 99.4% of treatments remained within predefined UF volume limits. Conclusions: Adaptive UF improved intradialytic RBV target attainment and individualized UF delivery within predefined treatment constraints. Prospective studies are required to determine whether these physiological improvements translate into clinical benefit.

Bernard Canaud, Alfred Gagel

OBJECTIVESTo describe the mechanistic basis, technical architecture, and operational determinants of HDF and to position high-volume postdilution HDF as a reference therapy in modern dialysis care.RESULTSPostdilution HDF combines diffusive and convective transport within a single dialyzer, enabling superior clearance of middle- and large-molecular-weight solutes compared with high-flux HD, combined even with a modestly improved small-solute removal. Convective efficiency is governed by the interplay between blood flow, plasma water flow, and filtration fraction, with optimal patient outcomes achieved at high convective volumes (i.e., ≥23 L/session), as there exists a dose-dependent correlation. The technique relies on a robust and inherently safe technical ecosystem, including ultrapure water systems, on-line production of sterile substitution fluid through multistage ultrafiltration, and advanced dialysis machines enabling precise volumetric control and real-time flow and pressure monitoring. High-volume postdilution HDF is associated with improved hemodynamic stability, reduced inflammation, and better clinical outcomes, including lower mortality and hospitalization rates, with a clear dose-response relationship.CONCLUSIONSPostdilution HDF represents a paradigm shift in extracorporeal therapy, integrating optimized transport mechanisms with advanced technical infrastructure to deliver a broader and more effective dialytic dose. When properly implemented, high-volume postdilution HDF should be considered a reference standard for personalized, efficient, and sustainable dialysis care.BACKGROUNDConventional hemodialysis (HD) remains limited in removing middle and large uremic toxins and is associated with substantial residual morbidity and mortality. On-line postdilution hemodiafiltration (HDF) has emerged as an advanced modality combining diffusion and convection to enhance solute clearance and clinical outcomes.METHODSNarrative review of physiological principles, transport mechanisms, and technical requirements underpinning HDF, integrated with current clinical evidence and engineering considerations.

Giovanni F M Strippoli, Giovanni Pellegrino, Jörgen Hegbrant, Paolo Fabbrini, Paolo Luca Maria Lentini, Filippo Aucella, Vincenzo Panichi, Maurizio Gallieni, Bernard Canaud, Andrew Davenport, Alberto Ortiz, Rosa Ramos, Jolanta Malyszko, Rümeyza Kazancıoğlu, Martin Kuhlman, Ana Carina Ferreira, Krister Cromm, Sagar Nigwekar, Allen R Nissenson, Luca De Nicola

RESULTSHigh-volume post-dilution HDF reduces all-cause mortality (hazard ratio 0.84; 95% CI 0 74-0.95; moderate-certainty evidence) and cardiovascular mortality (hazard ratio 0.78, 95% CI 0.64-0.96; moderate-certainty evidence; data from an individual participant data analysis of trials of high volume HDF versus high-flux HD). Emerging evidence suggests slower deterioration in selected patient-reported domains, including physical function, patient-perceived cognitive function, pain interference, and social participation (low-certainty evidence). Safety with on-line post-dilution HDF has been demonstrated to be similar to that of high-flux HD.CONCLUSIONSOnline post-dilution HDF should be regarded as a dose-dependent therapy. We recommend its use to reduce cardiovascular mortality and suggest high-volume HDF to reduce all-cause mortality and slow deterioration in selected patient-reported health domains. Effective implementation in clinical practice requires a targeted and individualized approach with careful optimization and monitoring of convective volume, along with appropriate treatment time, blood-flow rate, supporting infrastructure, and consideration of patient preferences. This guidance provides evidence-based recommendations and best practice statements for its use.BACKGROUNDOnline hemodiafiltration (HDF) enhances the removal of middle molecules, including large-middle molecules, through the combined action of diffusion and convection. Randomized controlled trials (RCTs) and individual participant data (IPD) meta-analyses demonstrate improved cardiovascular outcomes and, importantly, a reduction in all-cause mortality when HDF is delivered with sufficiently high convective volumes in post-dilution mode. These findings underscore that an adequate convective dose is a critical determinant of clinical benefits compared to high-flux hemodialysis (HD). However, translation into consistent clinical practice remains heterogeneous. Therefore, the Italian Society of Nephrology convened an international, multidisciplinary panel to synthesize randomized evidence comparing online post-dilution HDF with high-flux HD in adults receiving maintenance hemodialysis.METHODSThe critical outcomes included all-cause and cardiovascular mortality, whereas the important outcomes included selected patient-reported health domains, including physical function, patient-perceived cognitive function, pain interference, social participation, and health-related quality of life. The certainty of the evidence was appraised using the GRADE methodology. Structured guidance recommendations and best practice statements were developed through a consensus. Sensitivity analyses were performed to assess the robustness of the observed mortality effect.

Fernanda Salomão Gorayeb-Polacchini, Thyago Proença de Moraes, Rosilene Motta Elias, Allison Andrade, Dirceu Reis da Silva, Felipe Costa Neves, Fernando das Mercês de Lucas Junior, Isadora Cartaxo de Sousa Calvo, Juliana El Ghoz Leme, Maria Gabriela Guimarães, Pasqual Barretti, Patrícia Ferreira Abreu, Paulo Henrique Santos Fraxino, Ramon Lima, Stenio Barbosa de Freitas, Viviane Calice-Silva, José Andrade Moura-Neto

A diálise incremental, aplicável tanto à hemodiálise (HD) quanto à diálise peritoneal (DP), é uma abordagem individualizada que consiste em oferecer a dose de diálise ajustada à função renal residual (FRR) do paciente, de modo a alcançar os mesmos desfechos clínicos observados com doses plenas, porém, oferecendo melhor qualidade de vida e menor exposição aos riscos associados ao procedimento dialítico. Este Posicionamento da Sociedade Brasileira de Nefrologia (SBN) tem como objetivo apresentar recomendações sobre critérios de elegibilidade, prescrição, monitorização e implementação segura, bem como relatar os resultados clínicos já descritos com essa abordagem. A elegibilidade inclui uma diurese residual ≥ 500 mL/24h na HD ou ≥ 100 mL/24h na DP e/ou um clearance de ureia (Kru) ≥ 2,0 mL/min/1,73 m2, além de estabilidade clínica e controle volêmico e metabólico. Recomenda-se a monitorização com reavaliação regular da FRR. Os indicadores para intensificação da dose dialítica incluem hipervolemia, sintomas urêmicos, piora do estado nutricional, hiperpotassemia, hiperfosfatemia e acidose metabólica refratária, além de quadro laboratorial de subdiálise. A implementação da diálise incremental demanda protocolos institucionais bem definidos, educação sistemática de pacientes e familiares, uma equipe multiprofissional devidamente capacitada e um processo de decisão compartilhada. As evidências científicas sugerem que a diálise incremental é segura e efetiva, atenuando a perda da FRR, podendo reduzir hospitalizações, mantendo ou melhorando a qualidade de vida, sem aumentar a mortalidade. Adicionalmente, pode contribuir para a redução de custos e para a maior sustentabilidade do sistema de saúde, devendo ser considerada parte integrante do arsenal terapêutico contemporâneo.

Tiffany C Veinot, Megan Wickens, Edward Hennessey, Marissa Argentina, Kara Eggebrecht, Alicia Zerkle, Vu Le, Kelli Collins Damron, Lisa Velez, Jennifer Bragg-Gresham, Sarah L Krein, Dinesh Chatoth, Michael Heung, Brenda Gillespie, Barbara Murphy, Kai Zheng, Rajiv Saran

OBJECTIVESTo detail patient challenges, and how technology support addressed them, in a remote patient activation intervention for hemodialysis patients (n = 93) from trained patient mentors (n = 26).RESULTSAll mentees and 46.2% of mentors received support. Motivational access was targeted with explanations, rapport, and support availability. Study-provided, data-capable tablets enhanced material access, but internet access barriers persisted. Skills access was addressed by training; password-related challenges initially dominated. For usage access, on-demand technology support was balanced by engagement support: proactive prementoring session calls and login monitoring.MATERIALS AND METHODSUsing digital divide theory-derived codes, content analysis of: technology support program delivery data, hemodialysis clinic staff interviews, and support staff reflection papers. Descriptive statistics from postintervention mentee/mentor surveys.DISCUSSIONInterventionists should examine internet coverage in targeted areas, potentially using multiple carriers. A balance between password usability and security is required. Engagement support may be needed.CONCLUSIONTechnology support can close patient digital divides.

Smriti Arya, Signe Zhang, Xiao Fu

RESULTSRPM enables continuous monitoring of patient health data, promoting early detection of clinical issues and timely intervention. Reported benefits include improved patient engagement, treatment adherence, QoL, mortality, and reduced rates of hemodialysis transfers and hospitalization. RPM also supports more efficient communication between patients and healthcare providers. However, several challenges to broader implementation persist, including technological limitations, concerns regarding data privacy and security, and variable acceptance and adoption among patients and healthcare professionals.CONCLUSIONSIn conclusion, RPM has the potential to enhance home dialysis care by improving clinical outcomes, patient engagement, and healthcare efficiency. Addressing technological, privacy, adoption, and regulatory challenges will be critical to its broader implementation and long-term success.BACKGROUNDChronic kidney disease (CKD) patients on hemodialysis need continuous care, which has a minimal effect on their quality of life (QoL), as they have enormous symptomatic burdens, such as deprivation of sleep and anxiety, in addition to other consequences affecting their QoL. Moreover, managing dialysis patients is burdensome and costly. Telemedicine has recently gained popularity for electronically transferring data between patients and clinics. This has enabled remote monitoring of patients and timely intervention. Remote patient monitoring (RPM) is a noninvasive healthcare service designed to remotely manage patients' vital information and facilitate continuous data collection. The emergence of RPM has led to a transformative approach in the management of chronic conditions, particularly within the context of home dialysis for patients undergoing home hemodialysis (HHD) and peritoneal dialysis (PD).METHODSThis narrative review summarizes the current literature on the use of RPM in home dialysis settings. Relevant publications addressing RPM applications in HHD and PD were reviewed, and evidence was synthesized, with a focus on current practices, clinical outcomes, key advantages, limitations, and future directions for research and implementation, underscoring the potential of RPM to enhance care delivery in home dialysis.

Linda H Ficociello, Meijiao Zhou, Mianli Xiao, Hao Han, Michael S Anger, Jeffrey L Hymes, Dinesh Chatoth

Background: Effective fluid management is critical for improving outcomes in patients undergoing chronic hemodialysis (HD). Relative blood volume monitoring (RBVM) supports the optimization of ultrafiltration rate adjustments; however, real-world evidence evaluating its impact on hospitalizations in chronic HD is limited. Methods: We conducted a retrospective, propensity score-matched observational cohort study comparing patient outcomes across 165 Fresenius Kidney Care clinics with high RBVM utilization (HI-RBVM; >90% of treatments) matched to 165 clinics not using RBVM (NO-RBVM). Data were collected from July to December 2022. Primary outcomes were patient-level all-cause and fluid-related hospitalizations and hospitalization days over a 6-month follow-up. Multivariable scaled Poisson regression models were used to estimate adjusted incidence rates, rate ratios, and rate differences. Secondary outcomes included patient-level changes in monthly clinical measurements. Results: 24,958 patients were included (11,840 across HI-RBVM clinics; 13,118 across NO-RBVM clinics). Adjusted incidence rates were lower in the HI-RBVM group compared to the NO-RBVM group for all-cause hospitalizations (1.57 vs. 1.70 per person-year [ppy]), fluid-related hospitalizations (0.30 vs. 0.35 ppy), and hospitalization days (9.60 vs. 10.8 ppy), corresponding to 119 fewer hospital days per 100 patient-years (95% CI: -184, -54; p < 0.001). Among patients with dialysis vintage ≤6 months, those treated in HI-RBVM clinics had smaller increases in pre-HD weight (-0.03 kg vs. +0.46 kg; p = 0.008) and ultrafiltration volume (0.11 L vs. 0.21 L; p = 0.004), and underwent more frequent estimated dry weight (EDW) adjustments (mean 7.73 vs. 6.61; p < 0.001). Conclusions: Among HD patients, high RBVM utilization at the clinic level was associated with lower rates of hospitalization. Prospective or quasi-experimental studies are needed to determine causality.

Jeroen P Kooman, Maggie Han, Sabine H Josemans, Joris I Rotmans, Len Usvyat, Bernard Canaud, Peter Kotanko

Smartwatches are widely used by the general population as tools to promote wellness. Modern smartwatches can monitor arterial oxygen saturation, blood pressure, heart rate, arrhythmias, physical activity, sleep patterns, falls, and body composition. In individuals with chronic illnesses, smartwatches may support improved self-care and patient empowerment, support advanced phenotyping by providing digital biomarkers, enable early detection of clinically relevant changes in physiological parameters, and facilitate remote patient monitoring. Patients with chronic kidney disease, particularly those with kidney failure, often experience multiple abnormalities in physiological parameters and body functions. These disturbances may go undetected during routine clinical visits or hemodialysis (HD) treatments, yet they can significantly impact outcomes and may be amendable through therapeutic interventions. Especially when integrated with data from electronic health records and medical devices such as HD machines, smartwatches may be part of a digital ecosystem, supporting personalized precision care and patient empowerment. However, the use of smartwatches in healthcare can also produce false positive signals, which can lead to patient anxiety and potentially increase healthcare utilization and contribute to digital inequity. At present, the potential and challenges of smartwatches in kidney disease are largely unexplored. To fill this gap, this review aims to provide a comprehensive overview of smartwatch-based applications in health monitoring, highlighting both opportunities and limitations in patients with chronic kidney disease and kidney failure. Despite promises for future healthcare implementation, the lack of validation studies for clinical-grade measurements presently still precludes the use of smartwatches for clinical decision-making.

Sheng-Han Yueh, Jochen Raimann, Bernard Canaud, Meijiao Zhou, Xiaoling Ye, Ariella Mermelstein, Jeroen Kooman, Frank van der Sande, Len Usvyat, Peter Kotanko, Hanjie Zhang

RESULTSModels including BIS data showed excellent accuracy (R2 > 0.85), models excluding BIS features achieved inferior performance (R2 = 0.73-0.81). In models using BIS inputs, recent bioimpedance changes dominated feature importance. Models without BIS data relied primarily on urea distribution volume, age, and height.CONCLUSIONThese findings indicate that fluid volume compartments can be reliably estimated from routinely collected clinical data and history BIS measurements, offering valuable support for interim assessment of fluid status between scheduled BIS measurements.METHODUsing adult patients from the MONitoring Dialysis Outcomes (MONDO) 2012 cohort, we developed predictive models to estimate fluid volume compartments based on demographic data, laboratory values, treatment parameters, and multi-frequency whole-body bioimpedance spectroscopy (BIS) measurements. Clinical features were aggregated over an up-to-90-day look-back window, yielding 18,600 patients and 162,479 dialysis treatments. eXtreme Gradient Boosting (XGBoost) models were trained and tested using patient-level splits, with parallel models built either incorporating or excluding prior BIS measurements.BACKGROUNDOptimized fluid management is crucial in dialysis care because extracellular volume overload drives adverse cardiovascular outcomes. At the same time, comorbidities such as inflammation and protein energy wasting lead to decreased muscle mass and intracellular water. Accurate assessment of total body water (TBW) and its extracellular water (ECW) and intracellular water (ICW) compartments is therefore essential to guide ultrafiltration, evaluate dialysis adequacy, and monitor patient risk.

Josipa Zabcic, Fernando Salgado, Alcides Vilar, Jorge Moutinho, Thiemo Daldrup, Carsten Hornig

RESULTSCompared to the pre-monitoring period, breakdown rates decreased while mean time between failures increased. Unplanned service actions were reduced by 27%.DESIGNThe Clinics Predictive Maintenance tool was assessed in a field study (1235 machines in 34 dialysis units of a provider network) in Portugal between 2019 and 2023.CONCLUSIONSThe study shows that pre-emptive and timely servicing of haemodialysis equipment prevents disruptions of treatments by machine failures. The Clinics Predictive Maintenance tool enables staff to manage multiple patients and shifts throughout the day more effectively, mitigating potential risks associated with ineffective or improperly maintained equipment.OBJECTIVETo mitigate these problems, the Clinics Predictive Maintenance tool was devised to monitor the 'technical health' of haemodialysis machines throughout their operational life. The tool enables continuous and remote assessment of haemodialysis machines to predict failures, thereby allowing technicians to proactively schedule onsite servicing to replace affected components.BACKGROUNDSurvival and well-being of patients on haemodialysis depend on the provision of regular and effective therapy. Interruptions that shorten a haemodialysis session have adverse effect on patient outcomes. With increasing demands for haemodialysis, machines nowadays are in constant use with usually two or three daily shifts throughout the week. Increased machine malfunction is therefore inevitable, resulting in inadequate treatment and considerable stress for patients and care staff. Unplanned service demands are increasingly a reality. Service technicians often need to be summoned at short notice, but without full knowledge of the nature of the failure, appropriate spare parts often are unavailable on site, meaning that additional visits to replace components need to be planned.

Florentina Rosique, Laura Martínez-Alarcón, Guillermo Ramis, Leonor Andúgar, María Del Carmen Pérez, Alicia Araque, Fernando Hadad-Arrascue, Julio García-Puente, Daniel José Carbonell, Ramón Roca-Tey, Adoración Martínez-Losa, Juan B Cabezuelo

OBJECTIVES1) To assess the degree of agreement between Doppler ultrasound (DU) and the temperature gradient technique (TGT) for blood flow measurement (QA). 2) To evaluate the relative importance of different monitoring and/or surveillance methods for detecting significant stenosis using a predictive model.RESULTS80% were men and 20% women, with a mean age of 67.03 ± 10.25 years. 100% were hypertensive and 63.33% diabetic. 76.67% had a radiocephalic AVF and 23.33% a humeral AVF. The mean QA by TGT was 980.79 ± 63.86 ml/min and by DU 1098.43 ml/min. In the first sampling, 4 significant stenoses were detected, none in the second, and 3 in the third. In samplings 1 and 3, statistically significant differences were detected in the measurement of QA by TGT and ultrasound. No significant differences were found in any parameter measured by first-generation methods, except for PV in the first sampling. In the Bland-Altman analysis, a 96.7% agreement was observed between QA measurements by TGT and DU (p < 0.0001). The dot plot for the difference of each measurement from the mean for AVFs with QA > 1000 ml/min also showed agreement between both methods, with a deviation of only 4.34%. When first- and second-generation variables were introduced into the predictive model, four combinations with a significant Wilks' lambda were identified. The combination including QA determined by ultrasound was the most significant, with an overall correct classification of 80.5% when first-generation methods were included together with ultrasound-measured QA.CONCLUSIONIn our study, the agreement between QA measurement by TGT and Doppler ultrasound is high at all flow levels. Furthermore, the predictive model demonstrates that second-generation methods are superior to first-generation methods for the early detection of clinically significant stenosis.INTRODUCTIONThe most common complication of arteriovenous fistula (AVF) is stenosis, which can result in poorer hemodialysis (HD) outcomes and thrombosis. It is important to identify those stenoses at high risk of thrombosis in order to perform elective treatment to restore their function.METHODSA cross-sectional, comparative, observational study was conducted, in which the AVFs of 30 consecutive patients were assessed over a 3-month period, with monthly sampling. First-generation methods were applied, and second-generation methods using TGT and DU were used to measure QA.

Wiwat Chancharoenthana, Tanaya Siripoon, Supitcha Kamolratanakul, Viravarn Luvira, Weerapong Phumratanaprapin, Marcus J Schultz, Claudio Ronco, Punnee Pitisuttithum

SUMMARYLatent tuberculosis infection (LTBI) is common and preventable among patients with chronic kidney disease (CKD), where uremia and iatrogenic immunosuppression heighten reactivation risk. This narrative review synthesizes evidence across pre-dialysis CKD, dialysis, and kidney transplantation to propose a pragmatic care pathway. In advanced CKD, the tuberculin skin test performs poorly, whereas interferon-γ release assays (IGRAs) are preferred. Screening should be risk-targeted in pre-dialysis CKD, systematic at dialysis initiation, and mandatory pre-transplant for candidates and living donors. Following a positive test, clinicians must exclude active tuberculosis via clinical assessment and chest imaging before starting preventive therapy. Short-course rifamycin-based regimens (4 months of daily rifampin [4R], 3 months of once‑weekly isoniazid plus rifapentine [3HP], or 3 months of daily isoniazid plus rifampin [3HR]) enhance completion rates compared with 9 months of daily isoniazid (9H). In transplant recipients, rifamycin interactions with calcineurin and Mammalian target of rapamycin (mTOR) inhibitors typically favor 9H; rifamycins demand expert multidisciplinary management with intensive therapeutic drug monitoring. Programmatic data from dialysis units show high completion with tolerable toxicity, affirming routine feasibility. We integrate IGRA-based screening at critical transitions with tailored regimen selection, pyridoxine coadministration for isoniazid, and structured safety monitoring. Priorities include validating novel Mycobacterium tuberculosis antigen-based skin tests in CKD and developing implementation strategies to standardize renal care. We delineate setting-specific approaches for high- versus low-burden countries, addressing subclinical and incipient TB challenges in high-burden contexts. Adopting this framework can curb active TB progression, safeguard grafts, and enhance patient outcomes.

C Torino, Francesca Mallamaci, Pantelis Sarafidis, Marieta Thedorakopoulou M, Robert Ekart, Radovan Hojs, Olga Balafa, Filippo Aucella, Massimo Morosetti, Antonio Karpetas, Rocco Tripepi, Carmen Marino, Giovanni Tripepi, Carmine Zoccali

RESULTSOf 440 invited patients, 119 (27%) refused ABPM or could not undergo recording. Among the 321 who initiated ABPM, 29 (9%) did not complete the protocol, and 35 (11%) had inadequate recordings, so that 257 patients (80% of those starting ABPM and 58% of all invited) successfully completed valid 48-h ABPM. The most common symptoms reported were sleep interruption (32%), itching (24%), and pain during BP measurements (20%). Continuous pain and inability to sleep were significantly associated with the "dipping" BP phenotype.CONCLUSIONDespite strong guideline recommendations, 48-h ABPM is feasible in only about half of hemodialysis patients, with discomfort and sleep disturbance being the most frequently cited reasons for refusal among those declining ABPM and important barriers to both acceptance and completion in a subset of patients. These findings highlight the need for patient-centered approaches, supportive measures, and careful selection when implementing ABPM in the hemodialysis population, as well as the importance of integrating patient perspectives into clinical practice guidelines.BACKGROUNDAmbulatory blood pressure monitoring (ABPM) is recommended as the gold standard for assessing blood pressure (BP) in patients with chronic kidney disease (CKD) on hemodialysis, as it enables detection of masked and nocturnal hypertension, phenomena linked to adverse outcomes. However, the real-world feasibility and tolerability of extended ABPM protocols in this frail population remain unclear.METHODSWe conducted a multicenter, international survey inviting 440 consecutive adult in-center hemodialysis patients from eight nephrology units in Italy, Greece, and Slovenia. All patients were consecutively invited to undergo 48-h ABPM, with reasons for refusal or noncompletion systematically recorded. Tolerability and sleep disturbance were assessed using standardized questionnaires. ABPM was considered valid if at least 70% of measurements were obtained.

Alfred Gagel, Gerhard Wiesen, Stefano Stuard, Bernard Canaud

Background: Online hemodiafiltration (HDF) represents the most advanced form of kidney replacement therapy, combining diffusive and convective transport to enhance the removal of uremic toxins across a wide molecular spectrum. Achieving high convective volumes is a key determinant of treatment efficacy and has been associated with improved survival. Beyond small solutes, HDF targets middle molecules and protein-bound uremic toxins (PBUTs), including β2-microglobulin, inflammatory cytokines, and other large uremic compounds implicated in cardiovascular and systemic complications. Aims: This narrative review examines advances in dialysis membrane materials, dialyzer design, and monitoring technologies that optimize mass transfer in HDF. It focuses on the interplay between membrane permeability, hemocompatibility, and convective dose delivery, and discusses how these engineering developments translate into clinical performance. Key mechanisms: Recent progress in synthetic polymer membranes, particularly polysulfone- and polyethersulfone-based systems, and hollow-fiber manufacturing has enabled improved control of pore size distribution, hydraulic permeability, and sieving characteristics. These developments enhance the clearance of middle molecules and selected PBUTs while preserving essential proteins such as albumin. Mechanistic insights into internal filtration, protein polarization, and Donnan effects highlight the complex transport processes occurring within the dialyzer and their interaction with automated HDF systems. Expanded hemodialysis and high-volume HDF approaches further increase the removal of larger solutes but require careful management to limit albumin loss and maintain hemocompatibility. Clinical implications: Optimized membrane design, combined with advanced HDF machine algorithms, allows delivery of high convective volumes under safe and stable conditions, improving removal of β2-microglobulin, cytokines, and other clinically relevant toxins associated with inflammation and cardiovascular risk. However, treatment must remain individualized, considering electrolyte balance, albumin preservation, and patient-specific factors such as inflammation and nutritional status. Mechanistic modeling supports understanding of transport phenomena but must be interpreted cautiously when translated into clinical practice. Conclusions: Advances in membrane science, dialyzer engineering, and monitoring technologies have strengthened the role of HDF as a precision-based renal replacement therapy. Continued innovation aimed at optimizing middle-molecule and PBUT clearance while preserving albumin and treatment stability is essential to improve patient outcomes and support the broader implementation of HDF as a mainstream dialysis modality.

Xiao Fu, Yiting Shu, Yun Zhang

Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker extensively studied in multiple diseases. While its application in chronic kidney disease (CKD) and kidney transplant patients is relatively limited, NGAL has shown significant promise in the early detection and diagnosis of acute kidney injury (AKI), which may improve more timely management and potentially better clinical outcomes. In addition, NGAL has demonstrated promising utility in identifying peritoneal dialysis-related peritonitis (PDRP) and monitoring the treatment response. This review aims to provide an in-depth overview of the available research findings of NGAL in the management of AKI and PDRP, having these two conditions discussed together is particularly important for nephrologists who manage both conditions, especially to explore the potential of more specific NGAL forms, such as monomer NGAL and homodimer NGAL, to enhance early diagnosis and effective management of AKI and PDRP.

Vladimir Rigodon, Murilo Guedes, Peter G Pecoits, Brianna Hartley, Yue Jiao, Len A Usvyat, Dinesh K Chatoth, Jeffrey L Hymes, Franklin W Maddux, Jeroen Kooman, Thyago P Moraes, Jochen G Raimann, Peter Kotanko, John W Larkin, Roberto Pecoits-Filho

Background and objectivesIron plays a critical role beyond erythropoiesis, yet the prognostic significance of iron deficiency (ID) independent of anemia remains poorly defined in the peritoneal dialysis (PD) population. This study aimed to evaluate the association between iron status, specifically transferrin saturation (TSAT), and mortality in PD patients, independent of hemoglobin levels.Design, setting, participants, and measurementsWe conducted a retrospective cohort study of 11,013 adults who initiated PD at a large US dialysis network between December 2004 and January 2011. Patients had at least 180 days on PD and baseline data on TSAT, ferritin, hemoglobin, albumin, and white blood cell count. The primary outcome was all-cause mortality. Broadly adjusted associations between iron parameters and mortality were assessed using Cox proportional hazards models and restricted cubic splines, with adjustments for demographic, clinical, treatment-related, and laboratory variables including hemoglobin and ESA use.ResultsIron deficiency, defined as TSAT ≤20%, was present in 10% of patients at PD initiation. The cohort was 54% male and 70% Caucasian, with a mean age of 55 years; 39% had diabetes. While 91% received erythropoiesis-stimulating agents, only 34% received IV iron. After comprehensive adjustment, TSAT ≤20% remained independently associated with increased mortality (adjusted HR: 1.26; 95% CI: 1.12-1.42). Spline analyses showed a sharp rise in mortality risk at TSAT levels below 25%. Ferritin was inconsistently associated with mortality risk. During follow-up, 2704 deaths occurred (24.6% of the cohort) over a median 440-day follow-up.ConclusionsIron deficiency is common in incident PD patients and is associated with increased mortality risk, independent of anemia. These findings challenge current anemia-centric treatment paradigms and suggest that iron status, particularly TSAT, should be routinely assessed in PD patients regardless of hemoglobin levels. A prospective, randomized trial is warranted to evaluate whether proactive iron management improves outcomes in this population.

Jasmine Ion Titapiccolo, Max Botler, Francesco Bellocchio, Austin Vas, Felix Brockherde, Ricardo Peralta, Khaled Kahouli, Nathan Warren, Luca Neri

RESULTSMean age of patients was 68, and the average blood flow during the dialysis session was 352 ml/min. The model demonstrated excellent performance on independent testing datasets, achieving a sensitivity of 97.1%, specificity of 73.8%, and an overall accuracy of 82%. The area under the receiver operating characteristic curve (ROC-AUC) was 94%, reflecting strong discriminative ability. The model showed excellent calibration. Model performance across different experimental retraining folds indicates a stable and reliable training process.CONCLUSIONThe integration of this deep learning tool into clinical workflows could provide clinicians with a sensitive, objective, and time-efficient method for detecting high-pitched bruits which may be used in combination with other clinical signs for the detection of AVF complications such as stenosis. Implemented through a low-cost phono angiography protocol requiring minimal training, this approach has the potential to support earlier interventions and improve outcomes in the hemodialysis population.METHODAVF bruit recordings were collected from 65 patients across 12 dialysis centers in Europe and Asia using a digital stethoscope connected to the medical record of the patients. A deep learning model was developed to detect high-pitched bruits-an acoustic marker commonly associated with AVF stenosis. Expert-annotated recordings served as the reference standard for supervised training and evaluation.BACKGROUNDThe arteriovenous fistula (AVF) is the preferred vascular access for patients undergoing hemodialysis, and early identification of complications such as stenosis or dysfunction is essential to preserve access patency and reduce morbidity.

Afschin Gandjour, Dana Kendzia, Kevin Ho, Doris H Fuertinger, Carsten Hornig, Christian Apel, Jovana Petrovic Vorkapic

This study aimed to evaluate the cost-effectiveness and financial impact of an anemia management tool (AMT)-a software system that uses real-time blood volume and hemoglobin monitoring data-for adult patients receiving in-center hemodialysis (HD) in the United States. A Markov cohort model was developed to estimate lifetime costs and health outcomes for 1000 in-center HD patients with and without use of AMT. Clinical input parameters, including hemoglobin stability and dose reduction of erythropoiesis-stimulating agents (ESAs), were derived from a randomized controlled trial. The net monetary benefit (NMB) was calculated from the Medicare perspective, while a net financial impact analysis (NFIA) estimated provider-level savings based on ESA dose reductions, Quality Incentive Program (QIP)-related payment adjustments, and implementation costs. From the Medicare perspective, AMT yielded a positive NMB of $8419 per patient over a lifetime and remained cost-effective at a threshold of $2443 per patient per year. The NFIA showed an annual per-patient profit of $218. For a dialysis facility with 70 patients, this corresponds to an annual profit of $15,251. In conclusion, AMT is cost-effective from the Medicare perspective and financially beneficial for providers. Broader adoption may be supported by value-based reimbursement mechanisms and risk-sharing agreements to address residual uncertainties.

Samir C Gautam, Alaa S Awad, Vandana Dua Niyyar, Jennifer E Flythe, Emaad M Abdel-Rahman, Jochen G Raimann, Jobira A Woldemichael, Hiba I Sheikh, Raman Gaurav, Peter Kotanko, Xiwei Yang, Nihan Gencerliler, Jasmin Divers, Mariana Murea

BACKGROUND: Pragmatic randomized controlled trials (RCTs) must be embedded within routine clinical workflows, which require monitoring strategies that are feasible in everyday practice. Incremental hemodialysis—initiating treatment twice weekly in patients with preserved residual kidney function and escalating frequency as needed—differs from conventional thrice-weekly initiation. Implementing this approach in a pragmatic trial among providers and dialysis staff unfamiliar with incremental dialysis necessitated additional preparation and oversight. The TwoPlus trial is a multicenter pragmatic RCT evaluating incremental versus conventional initiation of chronic hemodialysis. We describe the patient monitoring framework developed for TwoPlus, which integrates digital infrastructure, human touchpoints, and provider engagement to ensure participant safety. METHODS/DESIGN: TwoPlus is an ongoing multicenter RCT enrolling adults initiating chronic hemodialysis with residual kidney function (urine urea clearance ≥ 2.0 mL/min and urine output ≥ 500 mL/24 hours). Participants are randomized to incremental hemodialysis—twice-weekly treatment supported by diuretics and sodium bicarbonate, with transition to thrice-weekly as clinically indicated—or conventional thrice-weekly initiation. The primary outcome is a composite of all-cause death, hospitalization, or emergency department visits. Secondary outcomes include preservation of residual kidney function and treatment adherence. The monitoring framework combines automated dialysis data downloads, manual data abstraction, assessments conducted by investigators or clinical research coordinators and reviewed at the site level, structured team reviews, and regular communication with treating providers. DISCUSSION: This layered monitoring model balances feasibility, safety, and fidelity in a pragmatic trial where provider engagement and site-specific adaptation were essential. The monitoring approach adopted in TwoPlus will inform the design of monitoring frameworks for future pragmatic nephrology trials. TRIAL REGISTRATION: NCT05828823.

Amanda DeMauro Renaghan, Marlies Ostermann, Claudio Ronco, Karen Ballen, Laura Cosmai, Roberta Fenoglio, Matteo Floris, Lui G Forni, Douglas E Gladstone, Ilya G Glezerman, Stuart L Goldstein, Shruti Gupta, Sandra M Herrmann, Edgar A Jaimes, Kenar D Jhaveri, Sabine Karam, Abhijat Kitchlu, Heather J Landau, Sheron Latcha, David E Leaf, Paolo Lentini, Jolanta Małyszko, Glen Markowitz, Naoka Murakami, Antonello Pani, Mark A Perazella, Arash Rashidi, Dario Roccatello, Elad Sharon, Ben Sprangers, Vladimír Tesař, Verônica Torres, Rimda Wanchoo, Andrew Whitman, Biruh T Workeneh, Diana Zepeda-Orozco, Mitchell H Rosner

In the past few decades, advances in understanding of cancer biology have led to the development of highly effective conventional chemotherapies, targeted therapies that act on specific pathways that are critical to cancer growth, immune-based therapies, and cellular therapies such as haematopoietic cell transplantation and chimeric antigen receptor T cell therapy. However, the nephrotoxic effects of these therapies continue to pose substantial challenges, with many unanswered questions regarding the prevention, diagnosis and management of this nephrotoxicity. Further, a lack of consensus and precise guidance on kidney function estimation and drug dosing for patients with acute kidney disease or chronic kidney disease and for patients receiving kidney replacement therapy limits access to life-saving therapies and jeopardizes outcomes. In this Consensus Statement, we present guidance on the prevention, diagnosis and management of anticancer therapy nephrotoxicity for adult patients that was developed at the 34th Acute Disease Quality Initiative meeting, which convened an international panel of experts in nephrology, haematology, oncology, nephropathology, critical care, paediatric care and pharmacology. We also define a research agenda focused on preventing and mitigating anticancer therapy toxicity, maximizing early detection of nephrotoxicity and enabling optimal drug dosing in patients with kidney disease, with the goal of advancing cancer care and fulfilling the potential of these ground-breaking treatments.

Barbara Marzell, Ulrich Tschulena, Ovidio Manuel Jimenez Martin, Fatih Kircelli

Historically, concerns about hypermagnesemia led to the reduction of dialysate magnesium (dMg) concentrations to below 0.75 mmol/L, effectively minimizing related adverse events. However, findings in recent years indicate that hypomagnesemia, defined as serum magnesium (sMg) levels below 0.7 mmol/L, has become more prevalent and a greater concern among dialysis patients, and has been associated with severe clinical outcomes, including vascular calcification and elevated mortality rates. Despite its significance, hypomagnesemia is often overlooked in clinical practice. This review highlights the critical importance of sMg levels in patients undergoing peritoneal dialysis (PD), particularly focusing on hypomagnesemia and hypermagnesemia. While causality has not been definitively established, evidence from the literature suggests that sMg levels should be monitored regularly and that increasing dMg concentrations from 0.25 to 0.5 or 0.75 mmol/L may help prevent hypomagnesemia, alongside nutritional management. Considering the impact of dMg on serum magnesium levels, and acknowledging the variability in reported outcomes, careful selection and individualization of dMg concentrations have the potential to impact clinical outcomes in PD patients.

Jennifer E Flythe, Cassandra B Picataggio, Leah Bernardo, Lorien S Dalrymple, Robert J Kossmann, Darren A DeWalt, Laura C Hanson, Virginia Wang, Mark L Unruh, Jesse Y Hsu, Laura M Dember

Individuals with hemodialysis-dependent kidney failure often suffer from numerous symptoms that contribute to poor patient outcomes. The Symptom Monitoring in Renal Replacement Therapy-Hemodialysis (SMaRRT-HD) Study is a pragmatic randomized trial of monitoring and follow-up of symptoms for individuals receiving maintenance hemodialysis. The trial uses an effectiveness-implementation hybrid design with randomization at the clinic level to compare the effectiveness of once monthly symptom monitoring with supported clinician follow-up via an electronic patient-reported outcome measure (ePROM) system called SMaRRT-HD compared to routine symptom monitoring without supported follow-up (Usual Care) to improve patient-reported and biomedical outcomes over a 12-month intervention period. This manuscript describes the design of the trial with a focus on the effectiveness evaluation component. The primary outcome is symptom severity ascertained with the Dialysis Symptom Index at 6 and 12 months. Secondary outcomes are additional patient-reported outcomes (PROs) including health-related quality of life, fatigue, pain, hemodialysis recovery time, depression, anxiety, and healthcare engagement and biomedical outcomes including hospitalizations, missed hemodialysis treatments, and shortened hemodialysis treatments. Exploratory outcomes include death and quality of communication between patients and clinicians. The trial will include up to 36 hemodialysis clinics located across the United States. The enrollment targets are 2400 participants for the Full Cohort from which the biomedical outcomes will be ascertained, and 1200 participants for the PRO Subset from which PROs will be ascertained. The findings of the trial will inform approaches to symptom monitoring and follow-up for people with hemodialysis-dependent kidney failure. Clinical Trials Registration Number: NCT05738330.

Carmine Zoccali, Francesca Mallamaci

The metaverse, a digital ecosystem characterized by the convergence of physical and virtual realities through technologies like virtual reality (VR), augmented reality (AR) and mixed reality, is reshaping societal and economic landscapes. In healthcare, the metaverse promises to revolutionize service delivery and medical education by overcoming geographical barriers and democratizing access to information. However, challenges such as the digital divide and privacy concerns persist. Economically, the metaverse is projected to significantly boost global GDP, with healthcare sectors poised for substantial growth through innovations like virtual clinics and telemedicine. In nephrology, the metaverse offers new avenues for patient education, treatment planning, and collaborative research. The integration of VR and AR technologies can enhance patient engagement by providing interactive platforms for understanding their condition, treatment options and lifestyle modifications. This approach empowers patients to take an active role in managing their health, potentially improving adherence to treatment regimens and overall outcomes. Furthermore, VR applications in hemodialysis have shown promise in reducing treatment-related symptoms and improving psychological well-being. The development of virtual clinics for chronic kidney disease patients could facilitate remote monitoring and management, reducing the need for emergency dialysis and improving long-term patient outcomes. Despite the burgeoning interest and research in this field, the integration of VR and AR into routine clinical practice remains in its nascent stages. The potential of these technologies to enhance patient care, improve surgical precision and provide immersive educational experiences is immense, paving the way for a future where technology and medicine are intricately linked.

Rui Lucena, Juliane Feurle, Célia Gil, Aníbal Ferreira, Pedro Ponce, Bernard Canaud

Water is an essential component of renal replacement therapy by dialysis. Haemodialysis patients undergoing 4-hour dialysis sessions, thrice weekly, may be exposed to more than 360 L of dialysis fluid per week. Dialysis water and ultrapure dialysis fluids have been established as a prerequisite for online convective therapies (namely haemodiafiltration), to improve biocompatibility of the dialysis system and to reduce inflammation profile of the dialysis patients. The microbial quality of dialysis water should be monitored regularly to demonstrate the effectiveness of the disinfection protocol. Current water and dialysis fluids microbial quality assessment is typically done via heterotrophic plate counts (HPC) and endotoxins analysis. Plate counts methodology provides information on the microbial content of the water only after a considerable incubation time (typically 7 days). Flow cytometry (FCM), as a rapid alternative method, provides the possibility of real-time corrective actions and greater patient safety. In this study, we compared the outcomes of dialysis water microbial quality in an existing dialysis clinic, using two different measurement methods, HPC and FCM, to test the possible benefits of applying FCM as a valid alternative method for dialysis water microbial monitoring. We conclude that FCM offers higher sensitivity than HPC for microbial monitoring of dialysis water, potentially enabling earlier corrective actions. More extensive and larger studies are needed, namely, to evaluate the possible added value of FCM method in dialysis fluids monitoring. If the FCM method is confirmed, it will be necessary to establish maximum allowable levels and typical action levels for dialysis water and dialysis fluids quality when using FCM.

Lucia Cattin, Sergio Lassola, Eleonora Balzani, Maria Salinas Rojo, Nicola Marchionna, Anna Lorenzin, Massimo De Cal, Monica Zanella, Claudio Ronco, Vinicio Danzi, Silvia De Rosa

RESULTSFluid overload and excessive ultrafiltration were associated with prolonged mechanical ventilation and extended hospital stays. Targeted fluid balance management reduced 90-day mortality risk by 50%. CRRT reduced hospital length of stay directly by 5.31 days but indirectly extended it by 11.78 days due to mechanical ventilation. Optimal fluid balance was critical for minimizing mortality and complications.CONCLUSIONSCareful and tailored fluid management in CRRT is essential for improving survival rates and clinical outcomes in septic shock patients. Continuous monitoring of fluid dynamics is necessary to optimize hemodynamic stability and avoid complications. Future multicenter studies are needed to validate these findings and refine fluid management protocols.INTRODUCTIONSepsis is a life-threatening condition characterized by dysregulated inflammatory responses, often leading to multiple organ dysfunction and high mortality rates. Continuous renal replacement therapy (CRRT) and extracorporeal blood purification therapies have emerged as vital adjuncts to manage fluid overload and modulate immune responses in septic shock. This study evaluates the impact of daily fluid balance variation on 90-day mortality and hospital length of stay in ICU patients undergoing CRRT for septic shock with endotoxin activity.METHODSA post hoc analysis of the EUPHAS 2 project was conducted on 61 ICU patients with nonresponsive endotoxin shock at San Bortolo Hospital (2016-2021). Bayesian joint models assessed the relationship between fluid balance and mortality. Mediation analysis explored the impact of CRRT on mechanical ventilation duration and hospital stay.

Silvia De Rosa, Sergio Lassola, Federico Visconti, Massimo De Cal, Lucia Cattin, Veronica Rizzello, Antonella Lampariello, Marina Zannato, Vinicio Danzi, Stefano Marcante

RESULTSAKI incidence at 72 h was 31%, varying across protocols. It was higher in the No TTM group at 24 h and in the TH and TTM groups during rewarming. Persistent serum creatinine elevation and fluid imbalance were notable in the TH group. Biomarkers indicated moderate tubular stress in the TTM and No TTM groups.CONCLUSIONSAKI is a frequent complication post-cardiac arrest, with the rewarming phase identified as critical for renal vulnerability. Tailored renal monitoring, biomarker-guided risk assessment, and precise temperature protocols are essential to improve outcomes.BACKGROUNDCardiac arrest (CA) is a leading cause of mortality and morbidity, with survivors often developing post-cardiac arrest syndrome (PCAS), characterized by systemic inflammation, ischemia-reperfusion injury (IRI), and multiorgan dysfunction. Acute kidney injury (AKI), a frequent complication, is associated with increased mortality and prolonged intensive care unit (ICU) stays. This study evaluates AKI incidence and progression in cardiac arrest patients managed with different temperature protocols and explores urinary biomarkers' predictive value for AKI risk.METHODSA prospective, single-center observational study was conducted, including patients with Return of Spontaneous Circulation (ROSC) post-cardiac arrest. Patients were stratified into three groups: therapeutic hypothermia (TH) at 33 °C, Targeted Temperature Management (TTM) at 35 °C, and no temperature management (No TTM). AKI was defined using KDIGO criteria, with serum creatinine and urinary biomarkers (TIMP-2 and IGFBP7) measured at regular intervals during ICU stay.

Paul Bennett, Madeleine Warren, Zehra Aydin, Joachim Beige, Elaine Bowes, Michael Cheung, Jeanette Finderup, Daniel Gallego, Manfred Hecking, Helen Hurst, Jennifer M King, Werner Kleophas, Anastasia Liossatou, Pedro Martins, Afra Masià-Plana, Yvette Meuleman, Luca Neri, Edita Noruišienė, John Ortiz, Marianne Rix, Stefano Stuard, Yusuke Tsukamoto

Adults with kidney failure receiving dialysis frequently report high symptom burden that can limit life participation and decrease the quality of life. Fatigue, itch, pain, anxiety, depressive symptoms, sleep problems, nausea, vomiting, muscle cramps, breathlessness, and decreased cognition can negatively impact important daily activities. Nurses are the majority health professional group that provides care for people receiving dialysis and have a major role in managing these symptoms. However, routine symptom management by nurses is not universal or standardized in dialysis care. In December of 2023, Kidney Disease: Improving Global Outcomes (KDIGO) held a workshop on the Nurse's Role in Managing the Symptoms of People Receiving Dialysis. The discussions focused on the current barriers nurses face when identifying and assessing symptoms, strategies for identifying symptoms, and the ongoing monitoring and management of symptoms. Nephrology nurses are pivotal in supporting the person with kidney failure receiving dialysis to minimize symptoms, optimize symptom management, decrease dialysis treatment burden, and improve life participation and quality of life.

Christopher Atzinger, Hans-Jürgen Arens, Luca Neri, Otto Arkossy, Mario Garbelli, Alina Jiletcovici, Robert Snijder, Kirsten Leyland, Najib Khalife, Mahmood Ali, Astrid Feuersenger

RESULTSIn total, 85,259 patients were included in the analysis; 59.9% were male, median (interquartile range) ESA starting dose was 733.3 (400.0, 1200.0) IU/week and follow-up duration was 2.2 (1.0, 4.2) years. Incidence of ESA hyporesponsiveness varied when applying different definitions; NICE 0.05/1000 days (5.2% of patients), ERI 0.40/1000 days (40.7%), KDIGO 0.15/1000 days (15.4%), and clinical practicality algorithm 0.48/1000 days (47.9%). ESA doses remained higher in hyporesponsive versus responsive patients, yet haemoglobin levels were similar between groups.Some people living with kidney disease may also have anaemia (low numbers of blood cells). This can increase their risk of heart disease and reduce their quality of life. Treatments for anaemia in people living with kidney disease include iron supplements and drugs that stimulate the production of red blood cells, known as erythropoiesis-stimulating agents. However, some people have weak responses to erythropoiesis-stimulating agents, and high doses can cause side effects. We looked at how the percentage of people with weak responses to erythropoiesis-stimulating agents varied when using different criteria to identify them. We also looked at the clinical characteristics of people who experienced a weak response after 1 year and those who did not. To do this, we reviewed medical records from people treated at specialist kidney care centres across 24 countries from Europe and South Africa. We included medical records between 1 January 2015 and 31 December 2021. Depending on what criteria we used, the percentage of people living with kidney disease and anaemia who were identified as having weak responses to erythropoiesis-stimulating agents varied greatly, from 5.2% to 47.9%. People living with kidney disease and anaemia who have weak responses to treatment with erythropoiesis-stimulating agents need adjustments to their care to address this. However, our research shows that the different criteria used to identify these patients can affect how many are identified, and may affect their care. Therefore, all patients with kidney disease and anaemia should be carefully monitored.TRIAL REGISTRATIONNCT05530291.CONCLUSIONThe results from this study, which applied multiple hyporesponsiveness definitions to a large, geographically diverse population of patients with anaemia of CKD, showed variation in ESA hyporesponsiveness incidence rates depending on definitions used and higher ESA doses in hyporesponsive versus responsive patients. These results underscore the need for individualised clinical assessment and thorough evaluation when considering ESA dose adjustments to reach haemoglobin targets. Graphical abstract available for this article.INTRODUCTIONHyporesponsiveness to erythropoiesis-stimulating agents (ESAs) in patients with anaemia of chronic kidney disease may lead to increased ESA doses to achieve target haemoglobin levels; however, elevated doses may be associated with increased mortality. Furthermore, patients with hyporesponsiveness to ESAs have poorer clinical outcomes than those who respond well to ESAs. Incidence and clinical characteristics of patients with ESA hyporesponsiveness were explored in a real-world setting.METHODSThis was a retrospective study of electronic medical records of adults with stage 5 chronic kidney disease receiving renal replacement therapy and ESA treatment, from 1 January 2015 to 31 December 2021. The primary objective was ESA hyporesponsiveness rate/1000 days, with a hyporesponsive event defined as ESA use at an elevated dose, according to National Institute for Health and Care Excellence (NICE) criteria. Other hyporesponsiveness definitions applied were erythropoietin resistance index-defined ESA hyporesponsiveness (ERI) Kidney Disease Improving Global Outcomes (KDIGO) and a clinical practicality algorithm.

Lihao Xiao, Hanjie Zhang, Juntao Duan, Xiaoran Ma, Len A Usvyat, Peter Kotanko, Yuedong Wang

COVID-19 has a higher rate of morbidity and mortality among dialysis patients than the general population. Identifying infected patients early with the support of predictive models helps dialysis centers implement concerted procedures (e.g., temperature screenings, universal masking, isolation treatments) to control the spread of SARS-CoV-2 and mitigate outbreaks. We collect data from multiple sources, including demographics, clinical, treatment, laboratory, vaccination, socioeconomic status, and COVID-19 surveillance. Previous early prediction models, such as logistic regression, SVM, and XGBoost, require sophisticated feature engineering and need improved prediction performance. We create deep learning models, including Recurrent Neural Networks (RNN) and Convolutional Neural Networks (CNN), to predict SARS-CoV-2 infections during incubation. Our study shows deep learning models with minimal feature engineering can identify those infected patients more accurately than previously built models. Our Long Short-Term Memory (LSTM) model consistently performed well, with an AUC exceeding 0.80, peaking at 0.91 in August 2021. The CNN model also demonstrated strong results with an AUC above 0.75. Both models outperformed previous best XGBoost models by over 0.10 in AUC. Prediction accuracy declined as the pandemic evolved, dropping to approximately 0.75 between September 2021 and January 2022. Maintaining a 20% false positive rate, our LSTM and CNN models identified 66% and 64% of positive cases among patients, significantly outperforming XGBoost models at 42%. We also identify key features for dialysis patients by calculating the gradient of the output with respect to the input features. By closely monitoring these factors, dialysis patients can receive earlier diagnoses and care, leading to less severe outcomes. Our research highlights the effectiveness of deep neural networks in analyzing longitudinal data, especially in predicting COVID-19 infections during the crucial incubation period. These deep network approaches surpass traditional methods relying on aggregated variable means, significantly improving the accurate identification of SARS-CoV-2 infections.

Laura Rosales Merlo, Xiaoling Ye, Hanjie Zhang, Brenda Chan, Marilou Mateo, Seth Johnson, Frank M van der Sande, Jeroen P Kooman, Peter Kotanko

RESULTSThe QIP group comprised 44 patients (59 ± 17 years), the concurrent control group 48 patients (59 ± 16 years), the historic control group 57 patients (58 ± 15 years). Six-month post-AVF creation, the fraction of non-censored patients with catheter in place was 21% in the QIP cohort, 67% in the concurrent control group, and 68% in the historic control group. In unadjusted and adjusted analysis, catheter residence time post-fistula creation was shorter in QIP patients compared to either control groups (p < 0.001).CONCLUSIONScvO2-based assessment of fistula maturation is associated with shorter catheter residence post-AVF creation.INTRODUCTIONArteriovenous fistula (AVF) maturation assessment is essential to reduce venous catheter residence. We introduced central venous oxygen saturation (ScvO2) and estimated upper body blood flow (eUBBF) to monitor newly created fistula maturation and recorded catheter time in patients with and without ScvO2-based fistula maturation.METHODSFrom 2017 to 2019, we conducted a multicenter quality improvement project (QIP) in hemodialysis patients with the explicit goal to shorten catheter residence time post-AVF creation through ScvO2-based maturation monitoring. In patients with a catheter as vascular access, we tracked ScvO2 and eUBBF pre- and post-AVF creation. The primary outcome was catheter residence time post-AVF creation. We compared catheter residence time post-AVF creation between QIP patients and controls. One control group comprised concurrent patients; a second control group comprised historic controls (2014-2016). We conducted Kaplan-Meier analysis and constructed a Cox proportional hazards model with variables adjustment to assess time-to-catheter removal.

Smeeta Sinha, Sagar U Nigwekar, Vincent Brandenburg, Lisa J Gould, Thomas E Serena, Sharon M Moe, George R Aronoff, Dinesh K Chatoth, Jeffrey L Hymes, Kevin J Carroll, Gabriela Alperovich, Laurence H Keller, Joan Perelló, Alex Gold, Glenn M Chertow

FUNDINGFunded by Sanifit, a CSL Vifor company.FINDINGSOverall, 34/37 patients randomised to hexasodium fytate and 26/34 patients randomised to placebo completed the 12-week randomised treatment period. At Week 12, both groups (hexasodium fytate versus placebo) showed similar improvements in BWAT-CUA (mean [standard deviation (SD)], -5.3 [5.2] versus -6.0 [6.2]; least squares mean difference, 0.3 [96% confidence interval (CI): -2.5, 3.0]; p = 0.88) and Pain VAS (mean [SD], -19.5 [26.9] versus -32.2 [38.5]; least squares mean difference, 11.5 [96% CI: -4.8, 27.8]; p = 0.15). One patient randomised to placebo briefly received hexasodium fytate in error. Serious adverse events through Week 12 included: calciphylaxis-related events leading to hospitalisation (2/38 [5%] versus 11/33 [33%]) and death (1/38 [3%] versus 5/33 [15%]). During the subsequent 12 weeks of open-label hexasodium fytate and 4 weeks of follow-up, there were no additional calciphylaxis-related events leading to hospitalisation. Over the course of the entire trial, deaths were 2/38 [5%] for the hexasodium fytate group and 7/33 [21%] for the placebo group.INTERPRETATIONIn patients with calciphylaxis, BWAT-CUA and Pain VAS improved similarly in hexasodium fytate- and placebo-treated patients; over the course of the entire trial, there were fewer deaths and calciphylaxis-related events leading to hospitalisation in the hexasodium fytate group.BACKGROUNDIn the CALCIPHYX trial, we investigated hexasodium fytate, an inhibitor of vascular calcification, for the treatment of calcific uraemic arteriolopathy (calciphylaxis), a rare condition characterised by painful, non-healing skin lesions.METHODSIn this international, phase 3, randomised, double-blind, placebo-controlled trial, adults with an ulcerated calciphylaxis lesion and pain visual analogue scale (VAS) score ≥50/100 were randomised 1:1 to hexasodium fytate 7 mg/kg or placebo intravenously during maintenance haemodialysis. Primary efficacy outcomes were an 8-item modification of the Bates-Jensen Wound Assessment Tool (BWAT-CUA) and Pain VAS in the intention-to-treat population. ClinicalTrials.gov number: NCT04195906.

Alan Y Hsu, Hou-Ting Kuo, Chun-Ju Lin, Ning-Yi Hsia, Shu-Chun Kuo, Chang-Ching Wei, Chun-Ting Lai, Huan-Sheng Chen, Yu-Hsun Wang, James Cheng-Chung Wei, Yi-Yu Tsai

RESULTSA total of 22 687 pediatric patients with uveitis (mean [SD] age, 10.3 [5.6] years; 54.2% male) and 22 687 comparators without uveitis (mean [SD] age, 10.3 [5.6] years; 54.5% male) were enrolled in the study. The risk of cataracts was increased among pediatric patients with uveitis up to a follow-up duration of 20 years (HR, 17.17; 95%CI, 12.90-22.80) from the index date. Subgroup analyses revealed an elevated cataract risk across age groups: 0 to 6 years (HR, 19.09; 95% CI, 10.10-36.00), 7 to 12 years (HR, 27.16; 95% CI, 15.59-47.20), and 13 to 18 years (HR, 13.39; 95% CI, 8.84-20.30); both female sex (HR, 13.76; 95% CI, 9.60-19.71) and male sex (HR, 11.97; 95% CI, 8.47-16.91); and Asian (HR, 13.80; 95% CI, 3.28-58.07), Black or African American (HR, 10.41; 95% CI, 5.60-19.36), and White (HR, 15.82; 95% CI, 11.05-22.60) race. Furthermore, increased cataract risks were also observed among those with and without a history of immunosuppressive agents (with: HR, 26.52 [95% CI, 16.75-41.90]; without: HR, 17.69 [95% CI: 11.39-27.40]), a history of steroid eye drop use (with: HR, 29.51 [95% CI, 14.56-59.70]; without: HR, 16.49 [95% CI, 11.92-22.70]), and a history of intraocular procedures (with: HR, 11.07 [95%CI, 4.42-27.71]; without: HR, 14.49 [95% CI, 10.11-20.70]).OBJECTIVETo describe factors associated with the development of cataracts among pediatric patients with uveitis.DESIGN, SETTING, AND PARTICIPANTSThis cohort study used the international TriNetX database to enroll pediatric patients with and without uveitis from January 1, 2002, to December 31, 2022. The nonuveitis cohort consisted of randomly selected control patients matched by age, sex, race and ethnicity, and specific comorbidities.CONCLUSIONS AND RELEVANCEIn this cohort study of pediatric patients with uveitis, an elevated risk of cataracts following a uveitis diagnosis was found compared with pediatric patients without uveitis. The findings suggest that pediatric patients with uveitis should be monitored for cataract development.IMPORTANCEThe long-term estimated risk of development of cataracts among pediatric patients with uveitis is not clear.MAIN OUTCOMES AND MEASURESThe primary outcome was the risk of developing cataracts among the uveitis group compared with the nonuveitis comparison group, with hazard ratios (HRs) and 95% CIs reported.EXPOSUREDiagnosis of uveitis, identified using diagnostic codes.

Bernard Canaud, Andrew Davenport, Hélène Leray-Moragues, Marion Morena-Carrere, Jean Paul Cristol, Jeroen Kooman, Peter Kotanko

Chronic kidney disease poses a growing global health concern, as an increasing number of patients progress to end-stage kidney disease requiring kidney replacement therapy, presenting various challenges including shortage of care givers and cost-related issues. In this narrative essay, we explore innovative strategies based on in-depth literature analysis that may help healthcare systems face these challenges, with a focus on digital health technologies (DHTs), to enhance removal and ensure better control of broader spectrum of uremic toxins, to optimize resources, improve care and outcomes, and empower patients. Therefore, alternative strategies, such as self-care dialysis, home-based dialysis with the support of teledialysis, need to be developed. Managing ESKD requires an improvement in patient management, emphasizing patient education, caregiver knowledge, and robust digital support systems. The solution involves leveraging DHTs to automate HD, implement automated algorithm-driven controlled HD, remotely monitor patients, provide health education, and enable caregivers with data-driven decision-making. These technologies, including artificial intelligence, aim to enhance care quality, reduce practice variations, and improve treatment outcomes whilst supporting personalized kidney replacement therapy. This narrative essay offers an update on currently available digital health technologies used in the management of HD patients and envisions future technologies that, through digital solutions, potentially empower patients and will more effectively support their HD treatments.

Grazia Maria Virzi, Maria Mattiotti, Sabrina Milan Manani, Maddalena Gnappi, Ilaria Tantillo, Valentina Corradi, Massimo De Cal, Anna Giuliani, Mariarosa Carta, Davide Giavarina, Claudio Ronco, Monica Zanella

RESULTSWe found strong correlations between peritoneal WBC, laboratory-based NGAL, and NGALds values, both overall and separated at each time point. On day 1, we observed no significant difference in WBC, both NGALds (p = 0.3, 0.9, and 0.2) between Gram-positive, Gram-negative, polymicrobial, and sterile peritonitis. No significant difference has been found between de novo versus relapsing peritonitis for all markers (p &gt; 0.05). We observed a parallel decrease of WBC and both NGAL in patients with favorable outcomes. WBC count and both pNGAL resulted higher in patients with negative outcomes (defined as relapsing peritonitis, peritonitis-associated catheter removal, peritonitis-associated hemodialysis transfer, peritonitis-associated death) at day 10 (p = 0.04, p = 0.03, and p = 0.05, respectively) and day 15 (p = 0.01, p = 0.04, and tendency for p = 0.005). There was a tendency toward higher levels of WBC and NGAL in patients with a negative outcome at day 5. No significant difference in all parameters was proven at day 1 (p = 0.3, p = 0.9, p = 0.2) between groups.CONCLUSIONThis study confirms pNGAL as a valid and reliable biomarker for the diagnosis of PD-peritonitis and its monitoring. Its trend is parallel to WBC count during peritonitis episodes, in particular, patients with unfavorable outcomes.INTRODUCTIONThe present study aimed to monitor peritoneal neutrophil gelatinase-associated lipocalin (pNGAL) during peritonitis episodes and to enhance its diagnostic value by evaluating pNGAL at scheduled times in parallel with white blood cell (WBC) count. In addition, we investigated possible correlations between pNGAL and the etiology of peritonitis, evaluating it as a possible marker of the clinical outcome.METHODSTwenty-two patients with peritoneal dialysis (PD)-related peritonitis were enrolled. Peritonitis was divided into Gram-positive, Gram-negative, polymicrobial, and sterile. WBC count and neutrophil gelatinase-associated lipocalin (NGAL) in PD effluent were measured at different times (days 0, 1, 5, 10, 15, and/or 20 and 10 days after antibiotic therapy discontinuation). NGAL was measured by standard quantitative laboratory-based immunoassay and by colorimetric NGAL dipstick (NGALds) (dipstick test).

Bernard Canaud, Allan Collins, Frank Maddux

Despite the significant progress made in understanding chronic kidney disease and uraemic pathophysiology, use of advanced technology and implementation of new strategies in renal replacement therapy, the clinical outcomes of chronic kidney disease 5 dialysis patients remain suboptimal. Considering residual suboptimal medical needs of short intermittent dialysis, it is our medical duty to revisit standards of dialysis practice and propose new therapeutic options for improving the overall effectiveness of dialysis sessions and reduce the burden of stress induced by the therapy. Several themes arise to address the modifiable components of the therapy that are aimed at mitigating some of the cardiovascular risks in patients with end-stage kidney disease. Among them, five are of utmost importance and include: (i) enhancement of treatment efficiency and continuous monitoring of dialysis performances; (ii) prevention of dialysis-induced stress; (iii) precise handling of sodium and fluid balance; (iv) moving towards heparin-free dialysis; and (v) customizing electrolyte prescriptions. In summary, haemodialysis treatment in 2030 will be substantially more personalized to the patient, with a clear focus on cardioprotection, volume management, arrhythmia surveillance, avoidance of anticoagulation and the development of more dynamic systems to align the fluid and electrolyte needs of the patient on the day of the treatment to their particular circumstances.

Carmine Zoccali, Francesca Mallamaci, Jean-Michel Halimi, Patrick Rossignol, Pantelis Sarafidis, Raffaele De Caterina, Robert Giugliano, Faiez Zannad

The association between cardiac and kidney dysfunction has received attention over the past two decades. A putatively unique syndrome, the cardiorenal syndrome, distinguishing five subtypes on the basis of the chronology of cardiac and kidney events, has been widely adopted. This review discusses the methodologic and practical problems inherent to the current classification of cardiorenal syndrome. The term "disorder" is more appropriate than the term "syndrome" to describe concomitant cardiovascular and kidney dysfunction and/or damage. Indeed, the term disorder designates a disruption induced by disease states to the normal function of organs or organ systems. We apply Occam's razor to the chronology-based construct to arrive at a simple definition on the basis of the coexistence of cardiovascular disease and CKD, the chronic cardiovascular-kidney disorder (CCKD). This conceptual framework builds upon the fact that cardiovascular and CKD share common risk factors and pathophysiologic mechanisms. Biological changes set in motion by kidney dysfunction accelerate cardiovascular disease progression and vice versa . Depending on various combinations of risk factors and precipitating conditions, patients with CCKD may present initially with cardiovascular disease or with hallmarks of CKD. Treatment targeting cardiovascular or kidney dysfunction may improve the outcomes of both. The portfolio of interventions targeting the kidney-cardiovascular continuum is in an expanding phase. In the medium term, applying the new omics sciences may unravel new therapeutic targets and further improve the therapy of CCKD. Trials based on cardiovascular and kidney composite end points are an attractive and growing area. Targeting pathways common to cardiovascular and kidney diseases will help prevent the adverse health effects of CCKD.

Faeq Husain-Syed, Tomonori Takeuchi, Javier A Neyra, Gonzalo Ramírez-Guerrero, Mitchell H Rosner, Claudio Ronco, Ashita J Tolwani

Approximately 20% of patients with acute brain injury (ABI) also experience acute kidney injury (AKI), which worsens their outcomes. The metabolic and inflammatory changes associated with AKI likely contribute to prolonged brain injury and edema. As a result, recognizing its presence is important for effectively managing ABI and its sequelae. This review discusses the occurrence and effects of AKI in critically ill adults with neurological conditions, outlines potential mechanisms connecting AKI and ABI progression, and highlights AKI management principles. Tailored approaches include optimizing blood pressure, managing intracranial pressure, adjusting medication dosages, and assessing the type of administered fluids. Preventive measures include avoiding nephrotoxic drugs, improving hemodynamic and fluid balance, and addressing coexisting AKI syndromes. ABI patients undergoing renal replacement therapy (RRT) are more susceptible to neurological complications. RRT can negatively impact cerebral blood flow, intracranial pressure, and brain tissue oxygenation, with effects tied to specific RRT methods. Continuous RRT is favored for better hemodynamic stability and lower risk of dialysis disequilibrium syndrome. Potential RRT modifications for ABI patients include adjusted dialysate and blood flow rates, osmotherapy, and alternate anticoagulation methods. Future research should explore whether these strategies enhance outcomes and if using novel AKI biomarkers can mitigate AKI-related complications in ABI patients.

Kianoush B Kashani, Linda Awdishu, Sean M Bagshaw, Erin F Barreto, Rolando Claure-Del Granado, Barbara J Evans, Lui G Forni, Erina Ghosh, Stuart L Goldstein, Sandra L Kane-Gill, Jejo Koola, Jay L Koyner, Mei Liu, Raghavan Murugan, Girish N Nadkarni, Javier A Neyra, Jacob Ninan, Marlies Ostermann, Neesh Pannu, Parisa Rashidi, Claudio Ronco, Mitchell H Rosner, Nicholas M Selby, Benjamin Shickel, Karandeep Singh, Danielle E Soranno, Scott M Sutherland, Azra Bihorac, Ravindra L Mehta

Acute kidney injury (AKI), which is a common complication of acute illnesses, affects the health of individuals in community, acute care and post-acute care settings. Although the recognition, prevention and management of AKI has advanced over the past decades, its incidence and related morbidity, mortality and health care burden remain overwhelming. The rapid growth of digital technologies has provided a new platform to improve patient care, and reports show demonstrable benefits in care processes and, in some instances, in patient outcomes. However, despite great progress, the potential benefits of using digital technology to manage AKI has not yet been fully explored or implemented in clinical practice. Digital health studies in AKI have shown variable evidence of benefits, and the digital divide means that access to digital technologies is not equitable. Upstream research and development costs, limited stakeholder participation and acceptance, and poor scalability of digital health solutions have hindered their widespread implementation and use. Here, we provide recommendations from the Acute Disease Quality Initiative consensus meeting, which involved experts in adult and paediatric nephrology, critical care, pharmacy and data science, at which the use of digital health for risk prediction, prevention, identification and management of AKI and its consequences was discussed.

Priscila Preciado, Laura Rosales Merlo, Hanjie Zhang, Jeroen P Kooman, Frank M van der Sande, Peter Kotanko

DISCUSSIONConcurrent combined monitoring of intradialytic ScvO2 and RBV change may provide additional insights into a patient's circulatory status. Patients with low ScvO2 and small changes in RBV may represent a specifically vulnerable group of patients at particularly high risk for adverse outcomes, possibly related to poor cardiac reserve and fluid overload.INTRODUCTIONIn maintenance hemodialysis (HD) patients, low central venous oxygen saturation (ScvO2 ) and small decline in relative blood volume (RBV) have been associated with adverse outcomes. Here we explore the joint association between ScvO2 and RBV change in relation to all-cause mortality.FINDINGSBaseline comprised 5231 dialysis sessions in 216 patients. The median RBV change was -5.5% and median ScvO2 was 58.8%. During follow-up, 44 patients (20.4%) died. In the adjusted model, all-cause mortality was highest in patients with ScvO2 below median and RBV change above median (HR 6.32; 95% confidence interval [CI] 1.37-29.06), followed by patients with ScvO2 below median and RBV change below median (HR 5.04; 95% CI 1.14-22.35), and ScvO2 above median and RBV change above median (HR 4.52; 95% CI 0.95-21.36).METHODSWe conducted a retrospective study in maintenance HD patients with central venous catheters as vascular access. During a 6-month baseline period, Crit-Line (Fresenius Medical Care, Waltham, MA) was used to measure continuously intradialytic ScvO2 and hematocrit-based RBV. We defined four groups per median change of RBV and median ScvO2 . Patients with ScvO2 above median and RBV change below median were defined as reference. Follow-up period was 3 years. We constructed Cox proportional hazards model with adjustment for age, diabetes, and dialysis vintage to assess the association between ScvO2 and RBV and all-cause mortality during follow-up.

Bernard Canaud, Jeroen Kooman, Andrew Davenport, David Campo, Eric Carreel, Marion Morena-Carrere, Jean-Paul Cristol

Cardiovascular disease (CVD) is a major burden in dialysis-dependent chronic kidney disease (CKD5D) patients. Several factors contribute to this vulnerability including traditional risk factors such as age, gender, life style and comorbidities, and non-traditional ones as part of dialysis-induced systemic stress. In this context, it appears of utmost importance to bring a closer attention to CVD monitoring in caring for CKD5D patients to ensure early and appropriate intervention for improving their outcomes. Interestingly, new home-used, self-operated, connected medical devices offer convenient and new tools for monitoring in a fully automated and ambulatory mode CKD5D patients during the interdialytic period. Sensoring devices are installed with WiFi or Bluetooth. Some devices are also available in a cellular version such as the Withings Remote Patient Monitoring (RPM) solution. These devices analyze the data and upload the results to Withings HDS (Hybrid data security) platform servers. Data visualization can be viewed by the patient using the Withings Health Mate application on a smartphone, or with a web interface. Health Care Professionals (HCP) can also visualize patient data via the Withings web-based RPM interface. In this narrative essay, we analyze the clinical potential of pervasive wearable sensors for monitoring ambulatory dialysis patients and provide an assessment of such toolkit digital medical health devices currently available on the market. These devices offer a fully automated, unobtrusive and remote monitoring of main vital functions in ambulatory subjects. These unique features provide a multidimensional assessment of ambulatory CKD5D patients covering most physiologic functionalities, detecting unexpected disorders (i.e., volume overload, arrhythmias, sleep disorders) and allowing physicians to judge patient's response to treatment and recommendations. In the future, the wider availability of such pervasive health sensing and digital technology to monitor patients at an affordable cost price will improve the personalized management of CKD5D patients, so potentially resulting in improvements in patient quality of life and survival.

Tiffany Christine Veinot, Brenda Gillespie, Marissa Argentina, Jennifer Bragg-Gresham, Dinesh Chatoth, Kelli Collins Damron, Michael Heung, Sarah Krein, Rebecca Wingard, Kai Zheng, Rajiv Saran

RESULTSThis study is funded by the Patient-Centered Outcomes Research Institute and approved by the University of Michigan Medical School's institutional review board. The study began enrolling patients in January 2023. Initial feasibility data will be available in May 2023. Data collection will conclude in November 2024.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)PRR1-10.2196/46187.CONCLUSIONSThe effects of provider and patient education on reducing the proportion of sessions with IDH and improving other patient-centered clinical outcomes will be evaluated, and the findings will be used to inform further improvements in patient care. Improving the stability of hemodialysis sessions is a critical concern for clinicians and patients with ESKD; the interventions targeted to providers and patients are predicted to lead to improvements in patient health and quality of life.TRIAL REGISTRATIONClinicalTrials.gov NCT03171545; https://clinicaltrials.gov/ct2/show/NCT03171545.OBJECTIVEThis study aims to evaluate the independent and comparative effectiveness of 2 interventions-one directed at hemodialysis providers and another for patients-in reducing the rate of IDH at hemodialysis facilities. In addition, the study will assess the effects of interventions on secondary patient-centered clinical outcomes and examine factors associated with a successful implementation of the interventions.BACKGROUNDEnd-stage kidney disease (ESKD) is treated with dialysis or kidney transplantation, with most patients with ESKD receiving in-center hemodialysis treatment. This life-saving treatment can result in cardiovascular and hemodynamic instability, with the most common form being low blood pressure during the dialysis treatment (intradialytic hypotension [IDH]). IDH is a complication of hemodialysis that can involve symptoms such as fatigue, nausea, cramping, and loss of consciousness. IDH increases risks of cardiovascular disease and ultimately hospitalizations and mortality. Provider-level and patient-level decisions influence the occurrence of IDH; thus, IDH may be preventable in routine hemodialysis care.METHODSThis study is a pragmatic, cluster randomized trial to be conducted in 20 hemodialysis facilities in the United States. Hemodialysis facilities will be randomized using a 2 × 2 factorial design, such that 5 sites will receive a multimodal provider education intervention, 5 sites will receive a patient activation intervention, 5 sites will receive both interventions, and 5 sites will receive none of the 2 interventions. The multimodal provider education intervention involved theory-informed team training and the use of a digital, tablet-based checklist to heighten attention to patient clinical factors associated with increased IDH risk. The patient activation intervention involves tablet-based, theory-informed patient education and peer mentoring. Patient outcomes will be monitored during a 12-week baseline period, followed by a 24-week intervention period and a 12-week postintervention follow-up period. The primary outcome of the study is the proportion of treatments with IDH, which will be aggregated at the facility level. Secondary outcomes include patient symptoms, fluid adherence, hemodialysis adherence, quality of life, hospitalizations, and mortality.

Luca Sgarabotto, Amir Kazory, Alessandra Brendolan, Luca Di Lullo, Monica Zanella, Claudio Ronco

RESULTSThe device's performance was as expected. Regarding the pediatric CVC, it was possible to perform measurements only with a Qb of 20 mL/min due to increased venous pressure. UF rates when lines were directly connected to the blood container as well as for CVC Tesio ranged from 3.7 to 11 mL/min, for the CVC Niagara™ from 4.5 to 12.5 mL/min, and for the CVC 7 Fr from 8.5 to 10 mL/min. The pressures of the vascular accesses were kept within a range of -5/-40 mm Hg for the artery and +10/+70 mm Hg for the vein. The highest venous pressure values were found with the CVC 7 Fr (+80/+100 mm Hg).MATERIALS AND METHODSThe AD 1 uses a polysulfone mini-filter to generate ultrafiltrate with the help of two forces: blood flow (Qb) and gravity (based on the height at which the ultrafiltrate collection bag is placed). In vitro experiments were performed using human blood to evaluate vascular access pressures and ultrafiltrate volumes using various central venous catheters (CVCs; 12 Fr bilume, 10 Fr with 2 separate lumens, pediatric catheter 7 Fr). A variety of combinations were tested with Qb of 20, 35, 50 mL/min and collection bag height at 20, 40, 60 cm, measuring the UF rate per minute while monitoring the pressures in the venous and arterial lines and filtration fraction.CONCLUSIONSThis novel device allows to treat patients with fluid overload in a variety of settings, from low-intensity department such as long-term care facilities to the intensive care unit. The device is small and portable, has a simple design, and is user friendly. Future studies will be needed to evaluate whether gentle UF and treatment of volume overload will translate into improvement in clinical outcomes such as a reduction in congestion-related hospital admissions.INTRODUCTIONFluid overload has been associated with untoward outcomes in a variety of clinical settings. Isolated extracorporeal ultrafiltration (UF) allows for mechanical extraction of excess fluid and optimization of volume status without the established risks associated with use of high-dose diuretics. Conventional machines for renal replacement therapy can be used to perform isolated UF. However, they typically need high blood flow rates with high circuit volumes and the therapy has to be performed by trained nurses. Herein, we describe a novel device, the Artificial Diuresis-1, or AD 1 (Medica S.p.A., Medolla, Italy), which is a portable technology designed to perform extracorporeal UF at bedside.

Grazia Maria Virzì, Maria Mattiotti, Sabrina Milan Manani, Maddalena Gnappi, Ilaria Tantillo, Valentina Corradi, Massimo de Cal, Anna Giuliani, Mariarosa Carta, Davide Giavarina, Claudio Ronco, Monica Zanella

No abstract available

Murilo Guedes, Brian Bieber, Indranil Dasgupta, Almudena Vega, Kosaku Nitta, Steven Brunelli, John Hartman, Jochen G Raimann, Bruce M Robinson, Ronald L Pisoni

Mineral bone disorder (MBD) is a frequent consequence of chronic kidney disease, more so in patients with kidney failure treated by kidney replacement therapy. Despite the wide availability of interventions to control serum phosphate and parathyroid hormone levels, unmet gaps remain on optimal targets and best practices, leading to international practice pattern variations over time. In this Special Report, we describe international trends from the Dialysis Outcomes and Practice Patterns Study (DOPPS) for MBD biomarkers and treatments from 2002-2021, including data from a group of 7 European countries (Belgium, France, Germany, Italy, Spain, Sweden, United Kingdom), Japan, and the United States. From 2002-2012, mean phosphate levels declined in Japan (5.6 to 5.2 mg/dL), Europe (5.5 to 4.9 mg/dL), and the United States (5.7 to 5.0 mg/dL). Since then, levels rose in the United States (to mean 5.6 mg/dL, 2021), were stable in Japan (5.3 mg/dL), and declined in Europe (4.8 mg/dL). In 2021, 52% (United States), 27% (Europe), and 39% (Japan) had phosphate >5.5 mg/dL. In the United States, overall phosphate binder use was stable (80%-84% over 2015-2021), and parathyroid hormone levels rose only modestly. Although these results potentially stem from pervasive knowledge gaps in clinical practice, the noteworthy steady increase in serum phosphate in the United States over the past decades may be consequential to patient outcomes, an uncertainty that hopefully will soon be addressed by ongoing clinical trials. The DOPPS will continue to monitor international trends as new interventions and strategies ensue for MBD management in chronic kidney disease.

Sheetal Chaudhuri, John Larkin, Murilo Guedes, Yue Jiao, Peter Kotanko, Yuedong Wang, Len Usvyat, Jeroen P Kooman

MATERIALS AND METHODSWe included data HD patients who had data across a baseline period of at least 1 year and 1 day in the internationally representative Monitoring Dialysis Outcomes (MONDO) Initiative dataset. Twenty-three input parameters considered in the model were chosen in an a priori manner. The prediction model used 1 year baseline data to predict death in the following 3 years. The dataset was randomly split into 80% training data and 20% testing data for model development. Two different modeling techniques were used to build the mortality prediction model.DISCUSSIONIn the internationally representative MONDO data for HD patients, we describe the development of a ML model and a traditional statistical model that was suitable for classification of a prevalent HD patient's 3-year risk of death. While both models had a reasonably high AUROC, the ML model was able to identify levels of hematocrit (HCT) as an important risk factor in mortality. If implemented in clinical practice, such proof-of-concept models could be used to provide pre-emptive care for HD patients.INTRODUCTIONSeveral factors affect the survival of End Stage Kidney Disease (ESKD) patients on dialysis. Machine learning (ML) models may help tackle multivariable and complex, often non-linear predictors of adverse clinical events in ESKD patients. In this study, we used advanced ML method as well as a traditional statistical method to develop and compare the risk factors for mortality prediction model in hemodialysis (HD) patients.FINDINGSA total of 95,142 patients were included in the analysis sample. The area under the receiver operating curve (AUROC) of the model on the test data with XGBoost ML model was 0.84 on the training data and 0.80 on the test data. AUROC of the logistic regression model was 0.73 on training data and 0.75 on test data. Four out of the top five predictors were common to both modeling strategies.

Dalia E Yousif, Xiaoling Ye, Stefano Stuard, Juan Berbessi, Adrian M Guinsburg, Len A Usvyat, Jochen G Raimann, Jeroen P Kooman, Frank M van der Sande, Neill Duncan, Kevin J Woollard, Rupert Bright, Charles Pusey, Vineet Gupta, Joachim H Ix, Peter Kotanko, Rakesh Malhotra

RESULTSWe studied 18,726 incident hemodialysis patients. Their age at dialysis initiation was 71.3 ± 11.9 years; 10,802 (58%) were males. Within the first 6 months, 2068 (11%) patients died, and 12,295 patients (67%) survived >36 months (survivor cohort). Hemodialysis patients who died showed a distinct biphasic pattern of change in inflammatory markers where an initial decline of inflammation was followed by a rapid rise that was consistently evident approximately 6 months before death. This pattern was similar in all patients who died and was consistent across the survival time intervals. In contrast, in the survivor cohort, we observed initial decline of inflammation followed by sustained low levels of inflammatory biomarkers.CONCLUSIONOur international study of incident hemodialysis patients highlights a temporal relationship between serial measurements of inflammatory markers and patient survival. This finding may inform the development of prognostic models, such as the integration of dynamic changes in inflammatory markers for individual risk profiling and guiding preventive and therapeutic interventions.INTRODUCTIONInflammation is highly prevalent among patients with end-stage kidney disease and is associated with adverse outcomes. We aimed to investigate longitudinal changes in inflammatory markers in a diverse international incident hemodialysis patient population.METHODSThe MONitoring Dialysis Outcomes (MONDO) Consortium encompasses hemodialysis databases from 31 countries in Europe, North America, South America, and Asia. The MONDO database was queried for inflammatory markers (total white blood cell count [WBC], neutrophil count, lymphocyte count, serum albumin, and C-reactive protein [CRP]) and hemoglobin levels in incident hemodialysis patients. Laboratory parameters were measured every month. Patients were stratified by survival time (≤6 months, >6 to 12 months, >12 to 18 months, >18 to 24 months, >24 to 30 months, >30 to 36 months, and >36 months) following dialysis initiation. We used cubic B-spline basis function to evaluate temporal changes in inflammatory parameters in relationship with patient survival.

Yirui Hu, Kunpeng Liu, Kevin Ho, David Riviello, Jason Brown, Alex R Chang, Gurmukteshwar Singh, H Lester Kirchner

Background: Hospitalization-associated acute kidney injury (AKI), affecting one-in-five inpatients, is associated with increased mortality and major adverse cardiac/kidney endpoints. Early AKI risk stratification may enable closer monitoring and prevention. Given the complexity and resource utilization of existing machine learning models, we aimed to develop a simpler prediction model. Methods: Models were trained and validated to predict risk of AKI using electronic health record (EHR) data available at 24 h of inpatient admission. Input variables included demographics, laboratory values, medications, and comorbidities. Missing values were imputed using multiple imputation by chained equations. Results: 26,410 of 209,300 (12.6%) inpatients developed AKI during admission between 13 July 2012 and 11 July 2018. The area under the receiver operating characteristic curve (AUROC) was 0.86 for Random Forest and 0.85 for LASSO. Based on Youden’s Index, a probability cutoff of >0.15 provided sensitivity and specificity of 0.80 and 0.79, respectively. AKI risk could be successfully predicted in 91% patients who required dialysis. The model predicted AKI an average of 2.3 days before it developed. Conclusions: The proposed simpler machine learning model utilizing data available at 24 h of admission is promising for early AKI risk stratification. It requires external validation and evaluation of effects of risk prediction on clinician behavior and patient outcomes.

Anna Lorenzin, Massimo de Cal, Matteo Marcello, David Sorbo, Sabrina Copelli, Claudio Ronco, Silvia de Rosa, Monica Zanella

RESULTSIn different experiments with various concentration of vancomycin, a maximum amount of 244 mg/g of sorbent was adsorbed reaching saturation between 60 and 80 min from the beginning of the experiments. The kinetics of adsorption appears to be governed by a Langmuir-like isotherm with maximal removal speed in the early minutes and a plateau after 60 min.INTRODUCTIONSepsis is a frequent complication in critically ill patients. Patients may require control of the source of infection, removal of pathogens and damaged cells, and organ support. Often, these targets can be achieved through the utilization of extracorporeal therapies including hemoperfusion for the adsorption of cytokines and other circulating mediators. On extracorporeal organ support, patients are generally treated with antibiotic therapy, and vancomycin is one of the most commonly used antibiotics. Because of the aspecific nature of adsorption, antibiotics can be removed from the circulation, leading to altered plasma levels and requiring prescription adjustment. The aim was to define the amount of vancomycin adsorbed by a sorbent cartridge (HA380, Jafron, China) during hemoperfusion and to establish possible strategies to maintain an effective plasma level in critically ill patients undergoing extracorporeal therapies.DISCUSSION/CONCLUSIONHA380 adsorbs significant amounts of vancomycin. Adjusting the achieved results with the experimental mini-module to a full-scale cartridge, a total of 25 g of antibiotic can be removed. This might have affected outcome results in clinical trials. This suggests prescribing administration to critically ill patients requiring hemoperfusion, immediately after or in the inter-session time window. In case of administration during hemoperfusion, adequate adjustment and plasma level monitoring is strongly recommended.METHODSIn vitro experiments with incremental concentrations of vancomycin in the test solution (500 and 1,000 mL) were carried out in a recirculation circuit until sorbent saturation was observed. A maximum of 10 g of vancomycin were injected and mini-modules containing 25 g of dry resin were utilized.

Xin Wang, Leticia M Tapia Silva, Milind Nikam, Sandip Mitra, Syed Shaukat Abbas Zaidi, Nadja Grobe

The aim of the paper is to summarize the current understanding of the molecular biology of arteriovenous fistula (AVF). It intends to encourage vascular access teams, care providers, and scientists, to explore new molecular tools for assessing the suitability of patients for AVF as vascular access for maintenance hemodialysis (HD). This review also highlights most recent discoveries and may serve as a guide to explore biomarkers and technologies for the assessment of kidney disease patients choosing to start kidney replacement therapy. Objective criteria for AVF eligibility are lacking partly because the underlying physiology of AVF maturation is poorly understood. Several molecular processes during a life cycle of an AVF, even before creation, can be characterized by measuring molecular fingerprints using newest "omics" technologies. In addition to hypothesis-driven strategies, untargeted approaches have the potential to reveal the interplay of hundreds of metabolites, transcripts, proteins, and genes underlying cardiovascular adaptation and vascular access-related adjustments at any given timepoint of a patient with kidney disease. As a result, regular monitoring of modifiable, molecular risk factors together with clinical assessment could help to reduce AVF failure rates, increase patency, and improve long-term outcomes. For the future, identification of vulnerable patients based on the assessment of biological markers of AVF maturation at different stages of the life cycle may aid in individualizing vascular access recommendations.

Bernard Canaud, Jeroen Kooman, Andreas Maierhofer, Jochen Raimann, Jens Titze, Peter Kotanko

New physiologic findings related to sodium homeostasis and pathophysiologic associations require a new vision for sodium, fluid and blood pressure management in dialysis-dependent chronic kidney disease patients. The traditional dry weight probing approach that has prevailed for many years must be reviewed in light of these findings and enriched by availability of new tools for monitoring and handling sodium and water imbalances. A comprehensive and integrated approach is needed to improve further cardiac health in hemodialysis (HD) patients. Adequate management of sodium, water, volume and hemodynamic control of HD patients relies on a stepwise approach: the first entails assessment and monitoring of fluid status and relies on clinical judgement supported by specific tools that are online embedded in the HD machine or devices used offline; the second consists of acting on correcting fluid imbalance mainly through dialysis prescription (treatment time, active tools embedded on HD machine) but also on guidance related to diet and thirst management; the third consist of fine tuning treatment prescription to patient responses and tolerance with the support of innovative tools such as artificial intelligence and remote pervasive health trackers. It is time to come back to sodium and water imbalance as the root cause of the problem and not to act primarily on their consequences (fluid overload, hypertension) or organ damage (heart; atherosclerosis, brain). We know the problem and have the tools to assess and manage in a more precise way sodium and fluid in HD patients. We strongly call for a sodium first approach to reduce disease burden and improve cardiac health in dialysis-dependent chronic kidney disease patients.

Andreas Maierhofer, Joachim Harlos, Bernard Canaud

Predialytic hyponatremia is associated with poor outcome in hemodialysis patients. Hypotonic hyponatremia is the most frequently encountered disorder reflecting mixed disorders combining extracellular fluid overload and free water excess, resulting from the interplay of intermittency of dialysis and diet observance, and likely precipitated by an acute or subacute illness. In this context, hyponatremia requires to be detected and worked up to identify and cure the cause. In this clinical case report, we describe preliminary results of using an online biosensor on a dialysis machine that provides automated predialysis plasma sodium concentration derived from dialysate conductivity measurements. Based on this biosensor, within a 5 year time frame, 11 patients out of more than 130 maintenance hemodialysis patients and over 40,000 dialysis sessions were identified with episodes of predialysis hyponatremia (≤135 mmol/l). In all patients, hyponatremic episodes were indicative of a severe underlying illness associated with fluid overload leading to plasma hypotonicity. Automated online predialysis plasma sodium concentration measurement offers an innovative, reliable, and cost-free tool that permits to detect hyponatremia as marker of an underlying illness development in dialysis patients. The value of this tool in supporting clinical decision-making deserves further studies in a large dialysis population.

Francesca Mallamaci, Rocco Tripepi, Claudia Torino, Giovanni Tripepi, Pantelis Sarafidis, Carmine Zoccali

RESULTSThe pre-awakening HR surge (r = - 0.46, P = 0.001) but not the corresponding BP surge (r = - 0.1, P = 0.98) was associated with LVMI and the risk of death [HR (1 unit): 0.89, 95% CI 0.83-0.96, P = 0.001]. The link between the pre-awakening HR surge with these outcome measures was robust and largely independent of established risk factors in the hemodialysis population, including the nocturnal dipping of BP. Weighted 24 h systolic BP and HR variability did not correlate with LVMI (all P > 0.11) nor with the risk of death (P > 0.11) and were also independent of the nocturnal dipping of systolic BP and HR.CONCLUSIONThis pilot study suggests that the low early morning changes in HR, likely reflecting enhanced sympathetic activity, entail a high risk for left ventricular hypertrophy (LVH) and mortality in the hemodialysis population.INTRODUCTIONAn exaggeration of the early morning increase in BP, a phenomenon accompanied by a parallel rise in heart rate (HR), is a marker of high cardiovascular risk. The early morning changes in these parameters have not been investigated in the hemodialysis population.METHODSIn a pilot, single center study including a series of 58 patients we measured the pre-awakening BP and HR surges and the nocturnal dipping of the same parameters as well as other established indicators of autonomic function (weighted 24 h systolic BP and HR variability) and tested their relationship with the left ventricular mass index (LVMI) and with the risk of death over a median follow up of 40 months.

Christian Verger, Claudio Ronco, Wim Van Biesen, James Heaf, François Vrtovsnik, Manel Vera Rivera, Ilze Puide, Raymond Azar, Adelheid Gauly, Saynab Atiye, Tatiana De Los Ríos

Objective: The nutritional status of patients on peritoneal dialysis (PD) is influenced by patient- and disease-related factors and lifestyle. This analysis evaluated the association of PD prescription with body composition and patient outcomes in the prospective incident Initiative for Patient Outcomes in Dialysis-Peritoneal Dialysis (IPOD-PD) patient cohort. Design and Methods: In this observational, international cohort study with longitudinal follow-up of 1,054 incident PD patients, the association of PD prescription with body composition was analyzed by using the linear mixed models, and the association of body composition with death and change to hemodialysis (HD) by means of a competing risk analysis combined with a spline analysis. Body composition was regularly assessed with the body composition monitor, a device applying bioimpedance spectroscopy. Results: Age, time on PD, and the use of hypertonic and polyglucose solutions were significantly associated with a decrease in lean tissue index (LTI) and an increase in fat tissue index (FTI) over time. Competing risk analysis revealed a U-shaped association of body mass index (BMI) with the subdistributional hazard ratio (HR) for risk of death. High LTI was associated with a lower subdistributional HR, whereas low LTI was associated with an increased subdistributional HR when compared with the median LTI as a reference. High FTI was associated with a higher subdistributional HR when compared with the median as a reference. Subdistributional HR for risk of change to HD was not associated with any of the body composition parameters. The use of polyglucose or hypertonic PD solutions was predictive of an increased probability of change to HD, and the use of biocompatible solutions was predictive of a decreased probability of change to HD. Conclusion: Body composition is associated with non-modifiable patient-specific and modifiable treatment-related factors. The association between lean tissue and fat tissue mass and death and change to HD in patients on PD suggests developing interventions and patient counseling to improve nutritional markers and, ultimately, patient outcomes. Study Registration: The study has been registered at Clinicaltrials.gov (NCT01285726).

John R Prowle, Lui G Forni, Max Bell, Michelle S Chew, Mark Edwards, Morgan E Grams, Michael P W Grocott, Kathleen D Liu, David McIlroy, Patrick T Murray, Marlies Ostermann, Alexander Zarbock, Sean M Bagshaw, Raquel Bartz, Samira Bell, Azra Bihorac, Tong J Gan, Charles E Hobson, Michael Joannidis, Jay L Koyner, Denny Z H Levett, Ravindra L Mehta, Timothy E Miller, Michael G Mythen, Mitra K Nadim, Rupert M Pearse, Thomas Rimmele, Claudio Ronco, Andrew D Shaw, John A Kellum

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.

Bernard Canaud, Xiaoling Ye, Len Usvyat, Jeroen Kooman, Frank van der Sande, Jochen Raimann, Yuedong Wang, Peter Kotanko

RESULTSWe included 23 495 HD patients; 3662 were incident. Females and older patients have lower baseline SCI. Higher SCI was associated with a lower risk of mortality [hazard ratio 0.81 (95% confidence interval 0.79-0.82)]. SCI decline accelerated ∼5-7 months before death. Lean tissue index (LTI) estimated by SCI was correlated with measured LTI in both sexes (males: R2 = 0.94; females: R2 = 0.92; both P < 0.001). Bland-Altman analysis showed that measured LTI was 4.71 kg/m2 (±2 SD: -12.54-3.12) lower than estimated LTI.CONCLUSIONSCI is a simple, easily obtainable and clinically relevant surrogate marker of MM in HD patients.METHODWe included all in-centre HD patients from 16 European countries with at least one SCI. The baseline period was defined as 30 days before and after the first multifrequency bioimpedance spectroscopy measurement; the subsequent 7 years constituted the follow-up. SCI was calculated by the Canaud equation. Multivariate Cox proportional hazards models were applied to assess the association of SCI with all-cause mortality. Using backward analysis, we explored the trends of SCI before death. Bland-Altman analysis was performed to analyse the agreement between estimated and measured MM.BACKGROUNDProtein-energy wasting, muscle mass (MM) loss and sarcopenia are highly prevalent and associated with poor outcome in haemodialysis (HD) patients. Monitoring of MM and/or muscle metabolism in HD patients is of paramount importance for timely detection of muscle loss and to intervene adequately. In this study we assessed the reliability and reproducibility of a simplified creatinine index (SCI) as a surrogate marker of MM and explored its predictive value on outcome.

Priscila Preciado, Leticia M Tapia Silva, Xiaoling Ye, Hanjie Zhang, Yuedong Wang, Peter Waguespack, Jeroen P Kooman, Peter Kotanko

RESULTSIntradialytic SaO2 was available in 52 patients (29 males; mean ± standard deviation age 66.5 ± 15.7 years) contributing 338 HD treatments. Mean time between onset of symptoms indicative of COVID-19 and diagnosis was 1.1 days (median 0; range 0-9). Prior to COVID-19 diagnosis the rate of HD treatments with hypoxemia, defined as treatment-level average SaO2 <90%, increased from 2.8% (2-4 weeks pre-diagnosis) to 12.2% (1 week) and 20.7% (3 days pre-diagnosis). Intradialytic O2 supplementation increased sharply post-diagnosis. Eleven patients died from COVID-19 within 5 weeks. Compared with patients who recovered from COVID-19, demised patients showed a more pronounced decline in SaO2 prior to COVID-19 diagnosis.CONCLUSIONSIn HD patients, hypoxemia may precede the onset of clinical symptoms and the diagnosis of COVID-19. A steep decline of SaO2 is associated with poor patient outcomes. Measurements of SaO2 may aid the pre-symptomatic identification of patients with COVID-19.BACKGROUNDMaintenance hemodialysis (MHD) patients are particularly vulnerable to coronavirus disease 2019 (COVID-19), a viral disease that may cause interstitial pneumonia, impaired alveolar gas exchange and hypoxemia. We ascertained the time course of intradialytic arterial oxygen saturation (SaO2) in MHD patients between 4 weeks pre-diagnosis and the week post-diagnosis of COVID-19.METHODSWe conducted a quality improvement project in confirmed COVID-19 in-center MHD patients from 11 dialysis facilities. In patients with an arterio-venous access, SaO2 was measured 1×/min during dialysis using the Crit-Line monitor (Fresenius Medical Care, Waltham, MA, USA). We extracted demographic, clinical, treatment and laboratory data, and COVID-19-related symptoms from the patients' electronic health records.

Mirko Belliato, Francesco Epis, Luca Cremascoli, Fiorenza Ferrari, Maria Giovanna Quattrone, Christoph Fisser, Maximilian Valentin Malfertheiner, Fabio Silvio Taccone, Matteo Di Nardo, Lars Mikael Broman, Roberto Lorusso

Mechanical power (MP) represents a useful parameter to describe and quantify the forces applied to the lungs during mechanical ventilation (MV). In this multi-center, prospective, observational study, we analyzed MP variations following MV adjustments after veno-venous extra-corporeal membrane oxygenation (VV ECMO) initiation. We also investigated whether the MV parameters (including MP) in the early phases of VV ECMO run may be related to the intensive care unit (ICU) mortality. Thirty-five patients with severe acute respiratory distress syndrome were prospectively enrolled and analyzed. After VV ECMO initiation, we observed a significant decrease in median MP (32.4 vs. 8.2 J/min, p < 0.001), plateau pressure (27 vs. 21 cmH2O, p = 0.012), driving pressure (11 vs. 8 cmH2O, p = 0.014), respiratory rate (RR, 22 vs. 14 breaths/min, p < 0.001), and tidal volume adjusted to patient ideal body weight (VT/IBW, 5.5 vs. 4.0 mL/kg, p = 0.001) values. During the early phase of ECMO run, RR (17 vs. 13 breaths/min, p = 0.003) was significantly higher, while positive end-expiratory pressure (10 vs. 14 cmH2O, p = 0.048) and VT/IBW (3.0 vs. 4.0 mL/kg, p = 0.028) were lower in ICU non-survivors, when compared to the survivors. The observed decrease in MP after ECMO initiation did not influence ICU outcome. Waiting for large studies assessing the role of these parameters in VV ECMO patients, RR and MP monitoring should not be underrated during ECMO.

Sabrina Milan Manani, Michele Baretta, Anna Giuliani, Grazia Maria Virzì, Francesca Martino, Carlo Crepaldi, Claudio Ronco

RESULTSThe case group presented a higher comorbidity score, according to Charlson Comorbidity Index (group A: 5.0; IQR 4.0-8.0 versus group B: 4.0; IQR 3.0-6.0) (p = 0.042). The results in group A showed a reduction in the urgent visits due to acute overhydration (group A: 0.17 ± 0.45 versus group B: 0.66 ± 1.36) (p: 0.042) and in the number of disease-specific hospitalization (group A n = 2.0; 18.2% versus group B n = 7.0; 77.8%) (p = 0.022). We did not find any difference between the two groups in terms of hospitalization because of all-cause, peritonitis, overhydration, and dropout. The analysis of KDQOL-SF subscales was similar in the two groups; on the contrary, the answers of our pointed questions have showed a significant difference between the two groups (group A: 100 IQR 87.5-100.0 versus group B 87.5; IQR 75.0-100.0) (p: 0.018).CONCLUSIONRM improved clinical outcomes in PD patients, reducing the emergency visits and the hospitalizations, related to nephrological problems, especially in patients with higher comorbidity score. The acceptance and satisfaction of care were better in patients monitored with RM than with standard APD.BACKGROUNDAutomated peritoneal dialysis (APD) has been proved benefit from remote monitoring (RM), but evidences are limited. In this study, we compared clinical outcomes and quality of life (QoL) in two group of patients undergoing APD, with and without exposure of RM.METHODSThis is a retrospective cohort study, comparing outcomes in two groups of APD patients monitored during 6 months with RM (group A: n = 35) or standard care (group B: n = 38 patients). In our clinical practice, we assign the RM system to patients who live more distant from the PD center or difficulty in moving. We evaluated emergency visits, hospitalizations, peritonitis, overhydration, and dropout. QoL was assessed with the Kidney Disease Quality of life-Short Form (KDQOL-SF). We included four additional questions focused on patient's perception of monitoring, safety and timely problems solution (Do you think that home-therapy monitoring could interfere with your privacy? Do you think that your dialysis sessions are monitored frequently enough? Do you think that dialysis-related issues are solved timely? Do you feel comfortable carrying out your home-based therapy?).

Marijke J E Dekker, Len A Usvyat, Constantijn J A M Konings, Jeroen P Kooman, Bernard Canaud, Paola Carioni, Daniele Marcelli, Frank M van der Sande, Vaibhav Maheshwari, Yuedong Wang, Peter Kotanko, Jochen G Raimann

Pre-hemodialysis systolic blood pressure variability (pre-HD SBPV) has been associated with outcomes. The association of a change in pre-HD SBPV over time with outcomes, and predictors of this change, has not yet been studied. Therefore, we studied this in a cohort of 8825 incident hemodialysis (HD) patients from the European Monitoring Dialysis Outcomes Initiative database. Patient level pre-HD SBPV was calculated as the standard deviation of the residuals of a linear regression model of systolic blood pressure (SBP) over time divided by individual mean SBP in the respective time periods. The pre-HD SBPV difference between months 1-6 and 7-12 was used as an indicator of pre-HD SBPV change. The association between pre-HD SBPV change and all-cause mortality in year 2 was analyzed by multivariate Cox models. Predictors of pre-HD SBPV change was determined by logistic regression models. We found the highest pre-HD SBPV tertile, in the first 6 months after initiation of HD, had the highest mortality rates (adjusted HR 1.44 (95% confidence intervals (95% CI): 1.15-1.79)). An increase in pre-HD SBPV between months 1-6 and 7-12 was associated with an increased risk of mortality in year 2 (adjusted HR 1.29 (95% CI: 1.05-1.58)) compared with stable pre-HD SPBV. A pre-HD SBPV increase was associated with female gender, higher mean pre-HD SBP and pulse pressure, and lower HD frequency.

Priscila Preciado, Hanjie Zhang, Stephan Thijssen, Jeroen P Kooman, Frank M van der Sande, Peter Kotanko

RESULTSWe studied 842 patients. During follow-up (median 30.8 months), 249 patients (29.6%) died. The following hourly RBV ranges were associated with improved survival: first hour, 93-96% [hazard ratio (HR) 0.58 (95% confidence interval (CI) 0.42-0.79)]; second hour, 89-94% [HR 0.54 (95% CI 0.39-0.75)]; third hour, 86-92% [HR 0.46 (95% CI 0.33-0.65)]. In about one-third of patients the RBV was within these ranges and in two-thirds it was above. Subgroup analysis by median age (≤/> 61 years), sex, race (white/nonwhite), predialysis systolic blood pressure (SBP; ≤/> 130 mmHg) and median interdialytic weight gain (≤/> 2.3 kg) showed comparable favorable RBV ranges. Patients with a 3-h RBV between 86 and 92% were younger, had higher ultrafiltration volumes and rates, similar intradialytic average and nadir SBPs and hypotension rates, lower postdialysis SBP and a lower prevalence of congestive heart failure when compared with patients with an RBV >92%. In the multivariate Cox analysis, RBV ranges remained independent and significant outcome predictors.CONCLUSIONSpecific hourly intradialytic RBV ranges are associated with lower all-cause mortality in chronic HD patients.BACKGROUNDRelative blood volume (RBV) monitoring is widely used in hemodialysis (HD) patients, yet the association between intradialytic RBV and mortality is unknown.METHODSIntradialytic RBV was recorded once/min during a 6-month baseline period; all-cause mortality was noted during follow-up. RBV at 1, 2 and 3 h into HD served as a predictor of all-cause mortality during follow-up. We employed Kaplan-Meier analysis, univariate and adjusted Cox proportional hazards models for survival analysis.

Jochen G Raimann, Xiaoling Ye, Peter Kotanko, John T Daugirdas

TESTS COMPAREDDuring the initial 8 months (baseline interval), average Kecn and URR were used to calculate a median patient-specific, modeled, calibration solute distribution volume (Vcal). During months 9 to 16 (period 1) and 17 to 24 (period 2), Kt/V was conventionally computed using URR and also by a new method using Vcal and Kecn without postdialysis SUN values. We examined the percentage error between these 2 methods of calculating Kt/V.RESULTSAmong 1,093 patients, mean individual-level median single-pool Kt/V values derived using the conventional method during the baseline interval, period 1, and period 2 were 1.62±0.24 (SD), 1.66±0.24, and 1.67±0.24, respectively. During periods 1 and 2, patient-level median Kt/V values derived using Kecn were 1.64±0.24 and 1.65±0.24, respectively. Percent differences between patient-level median values of Kt/V (conductivity minus conventional URR methods) were-0.63%±7.7% and-0.75%±8.4% for periods 1 and 2. Normalized protein nitrogen appearance were comparable between the 2 methods.CONCLUSIONSA new method of calculating Kt/V based on Kecn that requires fewer postdialysis SUN measurements provided diagnostic data comparable to those from conventional use of URR and has the potential to avoid errors related to postdialysis blood sampling and measurement.LIMITATIONSData were collected over 2 years. Study was limited to in-center hemodialysis patients dialyzed 3 times per week. Dialysis session length was not adjusted for treatment interruptions.STUDY DESIGNComparative study of 2 diagnostic tests.RATIONALE & OBJECTIVESConventional monitoring of hemodialysis dose is implemented using urea kinetic modeling based on single-pool Kt/V, which requires both pre- and postdialysis serum urea nitrogen (SUN) measurements. We compared this conventional approach to one in which Kt/V is calculated using conductivity clearance, thereby reducing the need for regular postdialysis SUN measurements.SETTING & PARTICIPANTSPrevalent patients receiving maintenance hemodialysis for at least 2 years for whom both urea reduction ratio (URR) and average conductivity clearance (Kecn) were measured.OUTCOMESConcordance between the 2 methods of calculating Kt/V.

Jochen G Raimann, Fang-I Chu, Sean Kalloo, Hanjie Zhang, Frank Maddux, Yuedong Wang, Peter Kotanko

RESULTSTwo subsets from initial 78,871 patients were studied. In Analysis 1 both AVF (referent) and AVG [HR 1.12 (0.97 to 1.30)] associated with a better outcome than CVC [HR 1.55 (1.38 to 1.74)] during follow-up. Lower mortality risk was seen for early switch from a CVC to AV access within the first 6 months [HR = 1.04 (0.97-1.13)] compared to a later switch [HR = 1.23 (1.10-1.38)]. Analysis 2 indicated that a CVC to AVF switch resulted in improved survival. Analysis 2 indicated early conversion to confer a survival benefit for CVC to AVG switch.DISCUSSION AND CONCLUSIONAVF and AVG show a survival benefit over CVC. Early conversion from CVC to either access improves survival. This emphasizes the importance of early preparation for dialysis by creation of an AVF or AVG and to convert CVCs early.BACKGROUNDHemodialysis initiation using a central venous catheter (CVC) poses an increased risk of death. Conversion to an arterio-venous graft or fistula (AVF, AVG) improves outcomes. The relationship of primary dialysis access and timing of conversion from CVC to either AVF or AVG to all-cause mortality was investigated.METHODSTwo retrospective analyses in incident hemodialysis patients commencing treatment from January 2010 to December 2014 in dialysis clinics in the United States were conducted. Analysis 1 stratified as per access at initiation and those commencing with CVC were further stratified into (a) those that had a CVC, AVF, or AVG the entire year; (b) those that were converted to either AVF or AVG within either (i) the first or (ii) the second 6 months. Kaplan Meier analysis and Cox regression analysis were employed. Analysis 2 included all CVC patients investigating the relationship between access conversion time and mortality risk using a Cox proportional hazards model depicting the hazard ratio (HR) as a spline function over time.

Elizabeth Katherine Batchelor, Pinelopi Kapitsinou, Pablo E Pergola, Csaba P Kovesdy, Diana I Jalal

Anemia is a complication that affects a majority of individuals with advanced CKD. Although relative deficiency of erythropoietin production is the major driver of anemia in CKD, iron deficiency stands out among the mechanisms contributing to the impaired erythropoiesis in the setting of reduced kidney function. Iron deficiency plays a significant role in anemia in CKD. This may be due to a true paucity of iron stores (absolute iron deficiency) or a relative (functional) deficiency which prevents the use of available iron stores. Several risk factors contribute to absolute and functional iron deficiency in CKD, including blood losses, impaired iron absorption, and chronic inflammation. The traditional biomarkers used for the diagnosis of iron-deficiency anemia (IDA) in patients with CKD have limitations, leading to persistent challenges in the detection and monitoring of IDA in these patients. Here, we review the pathophysiology and available diagnostic tests for IDA in CKD, we discuss the literature that has informed the current practice guidelines for the treatment of IDA in CKD, and we summarize the available oral and intravenous (IV) iron formulations for the treatment of IDA in CKD. Two important issues are addressed, including the potential risks of a more liberal approach to iron supplementation as well as the potential risks and benefits of IV versus oral iron supplementation in patients with CKD.

Luciano A Pedrini, Mario Comelli, Pio Ruggiero, Annalisa Feliciani, Vania Manfrini, Giorgio Cozzi, Angelo Castellano, Mauro Pezzotta, Guido Gatti, Marta Arazzi, Laura Auriemma, Attilio di Benedetto, Stefano Stuard

RESULTSIn sequence A, darbepoetin requirement decreased during Mixed HDF from 29.5 to 23.7 µg/month and increased significantly during Post-HDF (32.3 µg/month at 6th month) while, in sequence B, it increased during Post-HDF from 38.2 to 43.7 µg/month and decreased during Mixed HDF (23.9 µg/month at 6th month). Overall, EPO doses at 6 months on Mixed and Post-HDF were 23.8 and 38.4 µg/month, respectively, P < 0.01. A multiple linear model confirmed that Mixed HDF vs Post-HDF reduced significantly ESA requirement and ESA resistance (P < 0.0001), by a mean of 29% (CI 23-35%) in the last three months of the observation periods.CONCLUSIONSMixed HDF decreased darbepoetin-alfa requirement in dialysis patients. This might help preventing the untoward side effects of high ESA doses, besides having a remarkable economic impact. Additional evidence is needed to confirm this potential benefit of Mixed-HDF.BACKGROUNDImproved responsiveness to erythropoiesis stimulating agents (ESAs) in patients on on-line post-dilution hemodiafiltration (Post-HDF) compared with conventional hemodialysis (HD) was reported by some authors but challenged by others. This prospective, cross-over randomized study tested the hypothesis that an alternative infusion modality of HDF, mixed-dilution HDF (Mixed HDF), could further reduce ESAs requirement in dialysis patients compared to the traditional Post-HDF.METHODSOne-hundred-twenty prevalent patients from 6 Dialysis Centers were randomly assigned to two six-months treatment sequences: A-B and B-A (A, Mixed HDF; B, Post-HDF). Primary outcome was comparative evaluation of ESA (darbepoetin alfa) requirement and ESA resistance. Treatments efficiency, iron and vitamins status, inflammation and nutrition parameters were monitored.

Marijke Dekker, Constantijn Konings, Bernard Canaud, Paola Carioni, Adrian Guinsburg, Magdalena Madero, Jeroen van der Net, Jochen Raimann, Frank van der Sande, Stefano Stuard, Len Usvyat, Yuedong Wang, Xiaoqi Xu, Peter Kotanko, Jeroen Kooman

RESULTSWe included 8883 patients. In patients with pre-dialysis FO (>+1.1 to +2.5 L), pre-SBP <110 mmHg was associated with an increased risk of death {hazard ratio (HR) 1.52 [95% confidence interval (CI) 1.06-2.17]}. An increased risk of death was also associated with pre-dialysis fluid depletion (FD; <-1.1 L) combined with a pre-SBP <140 mmHg. In normovolemic (NV) patients, low pre-SBP <110 mmHg was associated with better survival [HR 0.46 (95% CI 0.23-0.91)]. Also, post-dialysis FD associated with a survival benefit. Results were similar when inflammation was present. Only high ultrafiltration rate could not explain the higher mortality rates observed.CONCLUSIONThe relation between pre-SBP and outcome is dependent on pre-dialysis FS. Low pre-SBP appears to be disadvantageous in patients with FO or FD, but not in NV patients. Post-dialysis FD was found to associate with improved survival. Therefore, we suggest interpreting pre-SBP levels in the context of FS and not as an isolated marker.BACKGROUNDPre-dialysis fluid overload (FO) associates with mortality and causes elevated pre-dialysis systolic blood pressure (pre-SBP). However, low pre-SBP is associated with increased mortality in haemodialysis patients. The objective of this study was to investigate the interaction between pre-dialysis fluid status (FS) and pre-SBP in association with mortality.METHODSWe included all patients from the international Monitoring Dialysis Outcome Initiative (MONDO) database with a pre-dialysis multifrequency bioimpedance spectroscopy measurement in the year 2011. We used all parameters available during a 90-day baseline period. All-cause mortality was recorded during 1-year follow-up. Associations with outcome were assessed with Cox models and a smoothing spline Cox analysis.

Laura M Dember, Eduardo Lacson, Steven M Brunelli, Jesse Y Hsu, Alfred K Cheung, John T Daugirdas, Tom Greene, Csaba P Kovesdy, Dana C Miskulin, Ravi I Thadhani, Wolfgang C Winkelmayer, Susan S Ellenberg, Denise Cifelli, Rosemary Madigan, Amy Young, Michael Angeletti, Rebecca L Wingard, Christina Kahn, Allen R Nissenson, Franklin W Maddux, Kevin C Abbott, J Richard Landis

RESULTSThe trial enrolled 7035 incident patients from 266 dialysis units. We discontinued the trial at a median follow-up of 1.1 years because of an inadequate between-group difference in session duration. For the primary analysis population (participants with estimated body water ≤42.5 L), mean session duration was 216 minutes for the intervention group and 207 minutes for the usual care group. We found no reduction in mortality or hospitalization rate for the intervention versus usual care.CONCLUSIONSAlthough a highly pragmatic design allowed efficient enrollment, data acquisition, and monitoring, intervention uptake was insufficient to determine whether longer hemodialysis sessions improve outcomes. More effective strategies for engaging clinical personnel and patients are likely required to evaluate clinical trial interventions that are fully embedded in care delivery.BACKGROUNDData from clinical trials to inform practice in maintenance hemodialysis are limited. Incorporating randomized trials into dialysis clinical care delivery should help generate practice-guiding evidence, but the feasibility of this approach has not been established.METHODSTo develop approaches for embedding trials into routine delivery of maintenance hemodialysis, we performed a cluster-randomized, pragmatic trial demonstration project, the Time to Reduce Mortality in ESRD (TiME) trial, evaluating effects of session duration on mortality (primary outcome) and hospitalization rate. Dialysis facilities randomized to the intervention adopted a default session duration ≥4.25 hours (255 minutes) for incident patients; those randomized to usual care had no trial-driven approach to session duration. Implementation was highly centralized, with no on-site research personnel and complete reliance on clinically acquired data. We used multiple strategies to engage facility personnel and participating patients.

Sabrina Milan Manani, Carlo Crepaldi, Anna Giuliani, Grazia Maria Virzì, Marta Proglio, Claudio Ronco

Chronic diseases are a global concern and a leading cause of death and disability. These conditions require intensive and ongoing medical assistance to maximize outcomes and avoid the risk of frequent flare-ups and hospitalizations, which increase the cost of healthcare. Remote patient management (RPM) is a strategy that allows for accurate home monitoring of chronic patients, enabling the team to improve care through prevention and early identification of problems, with consequent timely interventions. Peritoneal dialysis (PD) is a home-based therapy representing an ideal model for testing the ability of RPM to improve clinical outcomes by allowing the 2-way link between health providers and patients. The literature and our own results confirm that RPM applied to automated peritoneal dialysis (APD) allows an efficient use of healthcare resources, helping to improve tailoring of APD prescription and to intervene early with troubleshooting, reducing the frequency of in-person visits for emergency problems. RPM-APD is today made possible by a cloud-based software providing bidirectional communication between patient's home and the hospital care team (Cycler HOMECHOICE CLARIA with SHARESOURCE platform). This approach can be useful in promptly identifying patients with higher risk of complications: a knowledge-based management permits the reduction of urgent events, and the prevention of clinical complications improving patient outcomes. In our experience, matured over 2 years in a cohort of prevalent patients, we observed a significant reduction of patient drop-out and technique failure, the number of scheduled and unscheduled hospital visits, the number of episodes of overhydration, rate of hospitalization, episodes of non-compliance to prescription, patient and hospital team time spent in travelling and management of therapy, healthcare costs and patient's expenditure, miles travelled by patients from home to hospital and vice versa. The cost/benefit analysis is strongly in favor of the RPM-APD modality versus the traditional periodic hospital visit regime.

Amanda K Leonberg-Yoo, Weiling Wang, Daniel E Weiner, Eduardo Lacson

DISCUSSIONConsumption of ONS during HD sessions is associated with reduced hospital readmission rates among in-center maintenance HD with severe hypoalbuminemia at 30 days post-hospital discharge.INTRODUCTIONHemodialysis (HD) patients are hospitalized nearly twice yearly, and 35% of these patients are rehospitalized within 30-days postdischarge. We hypothesized that monitored oral nutritional supplementation (ONS) during HD treatment may decrease readmissions.FINDINGSOf 5479 eligible patients, ONS was prescribed to 1420 individuals. Mean age was 64.6 ± 14.1 (SD) years; median dialysis vintage was 3.9 years. There were 274 (19%) readmissions among ONS recipients vs. 1571 (38.7%) among controls during the 30-day follow-up period. Individuals who did not receive ONS had increased odds of readmission [OR 2.26 (95% CI 1.02, 2.53)] in 30 days, as compared to those who did receive ONS postdischarge. In sensitivity analyses using a propensity score matched cohort, the odds ratio of readmissions within 30 days postdischarge was 1.71 (95% CI: 1.42, 2.07) for individuals who did not receive ONS as compared to those who received ONS.METHODSA cohort of maintenance HD patients, treated at a large dialysis organization, who were hospitalized with a postdischarge albumin of ≤3.5 g/dL, without documented ONS use 90 days prior to the index hospitalization were identified. Individuals who received monitored intradialytic ONS postdischarge were compared to those without receipt of ONS. The outcome of interest was 30-day hospital readmissions. Logistic regression was used to assess the association between ONS receipt and 30-day readmission events, with adjustment for case-mix and laboratory variables.

Sabrina Milan Manani, Mitchell H Rosner, Grazia Maria Virzì, Anna Giuliani, Sonia Berti, Carlo Crepaldi, Claudio Ronco

RESULTSChanges in APD prescription were almost double in the case group (RM) compared to the control group (p = 0.0005). The need for in-person visits and nocturnal alarms was significantly less in RM-APD than in traditional APD (p = 0.01 and p = 0.002, respectively). The distance traveled by patients in the case of RM-APD was reduced by 1,134 km with a time saving of 1,554 min for patients. The overall cost reduction for the PD center in terms of time/nurse and time/physician was 2,647 and 3,673 min, respectively. All these advantages were obtained in the presence of an improved technique survival with a significant reduction of dropouts. All patients found that it is easy to use the RM system and were satisfied with the high level of interaction with the care team and with the possibility of timely resolving technical problems.CONCLUSIONThese data confirm the long-term benefits of RM applied to APD. RM-APD is cost-effective; it allows early detection and resolution of problems, improved treatment compliance, reduction of patient's access to hospital center for technical and clinical complications with consequent savings, and improved patient's quality of life.BACKGROUNDPeritoneal dialysis (PD) is an ideal model for testing remote monitoring (RM). In this study, we evaluated the RM application longitudinally in stable patients undergoing automated PD (APD).METHODSThis was an observational study, comparing outcomes in patients with (current patients) and without (historical data) exposure of RM. We analyzed cost-effectiveness of RM-APD measuring the number of night alarms, number of hospital visits, direct and indirect costs.

Pedro Jesús Labrador Gómez, Silvia González Sanchidrián, Jorge Labrador Gómez, Juan Ramón Gómez-Martino Arroyo, María Carmen Jiménez Herrero, Santiago José Abraham Polanco Candelario, Jesús Pedro Marín Álvarez, Sandra Gallego Domínguez, Elena Davin Carrero, José María Sánchez Montalbán, Inés Castellano Cerviño, Mitchell H Rosner, Claudio Ronco

RESULTSIn six months, 1241 alerts from 11,022 admissions were issued. Overall incidence of AKI was 7.7%. Highest AKI stage reached was: stage 1 (49.8%), 2 (24.5%) and 3 (25.8%), in-hospital mortality was 10.9%, 22.7%, 33.9% respectively and 57.1% in AKI requiring dialysis; mortality in stable CKD was 4.3%. Median LOS was 8 days versus 5 days for all patients. AKI was associated with a mortality of 3.18 (95% CI 1.80-5.59) and a LOS 1.52 (1.11-2.08) times as high as that for admissions without AKI. Multivariate analysis indicated that a LOS higher than 8 days was associated with AKI. Previous CKD was noted in 31.9% and AKI in 45.3% at discharge. As compared to the use of the detect system, only one third of CKD patients and half of AKI episodes were identified.CONCLUSIONSCKD and in-hospital AKI are under-recognized entities. Mortality and LOS are increased in-hospital patients with renal dysfunction. AKI severity was associated with higher mortality and LOS. An automated electronic detection system for identifying renal dysfunction would be a useful tool to improve renal outcomes.BACKGROUND AND AIMSAcute kidney injury (AKI) is associated with higher mortality and length of stay (LOS) for hospitalized patients. To improve outcomes, an electronic detection system could be a useful tool for early diagnosis.METHODSA fully automated real-time system for detecting decreased glomerular filtration rate in adult patients was developed in our hospital, DETECT-H project. AKI was established according to KDIGO guidelines.

Xiaoling Ye, Jeroen P Kooman, Frank M van der Sande, Bernard Canaud, Stefano Stuard, Michael Etter, Xiaoqi Xu, Cristina Marelli, Adrian Guinsburg, Albert Power, Len A Usvyat, Yuedong Wang, Peter Kotanko, Jochen G Raimann

RESULTSWe included 20,216 patients in the study. A SNa ≤135 mEq/L was observed to be the strongest predictor of evaluated mortality risk. Higher SNa variability (quantified as SD, ARV, and DR) was also associated with an increased mortality irrespective of SNa levels. When compared with higher SD or ARV, greater DR showed a stronger association with an elevated risk of death. Controlling the Cox Proportional hazard models for additional parameters showed consistent results.CONCLUSIONHigher SNa variability associated with increased all-cause mortality at all levels of SNa. DR of SNa showed the strongest association with mortality and may constitute a Simple and novel prognostic indicator, easily applicable at the bedside.BACKGROUNDLow serum sodium (SNa) is associated with an increased mortality in chronic hemodialysis (HD) patients. Dialysis patients are thought to have an individual pre-dialysis SNa set-point, yet there is evidence for variability of pre-dialysis SNa in individual patient. In this study, we explored the association of several SNa variability metrics with all-cause mortality in a large patient population from the international MONitoring Dialysis Outcomes (MONDO) Initiative.METHODSAll adult incident patients from the MONDO database with more than 5 SNa measurements during the first year on HD were included. All patients were required to survive the first year on HD (defined as the baseline). During the subsequent 2 years of follow-up, all-cause mortality was recorded. The following variability indicators were calculated during baseline: mean SNa and its SD; average real variability (ARV, average the absolute distance of the 2 consecutive SNa measurements), and average directional range (DR, the difference between minimum and maximum values). We used Cox Proportional hazard model with bivariate spline terms to analyze the joint association of SNa and SD, ARV and DR, respectively, with all-cause mortality. While conducting the multivariate Cox regression analyses, patients were stratified into 3 groups of DR (Negative DR: -20≤ DR ≤ -6, Null DR: -6< DR < 6 and Positive DR: 6≤ DR ≤20) with the Null DR as the reference group.

Jeroen P Kooman, Len A Usvyat, Marijke J E Dekker, Dugan W Maddux, Jochen G Raimann, Frank M van der Sande, Xiaoling Ye, Yuedong Wang, Peter Kotanko

Patients with end-stage renal disease (ESRD) experience unique patterns in their lifetime, such as the start of dialysis and renal transplantation. In addition, there is also an intricate link between ESRD and biological time patterns. In terms of cyclic patterns, the circadian blood pressure (BP) rhythm can be flattened, contributing to allostatic load, whereas the circadian temperature rhythm is related to the decline in BP during hemodialysis (HD). Seasonal variations in BP and interdialytic-weight gain have been observed in ESRD patients in addition to a profound relative increase in mortality during the winter period. Moreover, nonphysiological treatment patters are imposed in HD patients, leading to an excess mortality at the end of the long interdialytic interval. Recently, new evidence has emerged on the prognostic impact of trajectories of common clinical and laboratory parameters such as BP, body temperature, and serum albumin, in addition to single point in time measurements. Backward analysis of changes in cardiovascular, nutritional, and inflammatory parameters before the occurrence as hospitalization or death has shown that changes may already occur within months to even 1-2 years before the event, possibly providing a window of opportunity for earlier interventions. Disturbances in physiological variability, such as in heart rate, characterized by a loss of fractal patterns, are associated with increased mortality. In addition, an increase in random variability in different parameters such as BP and sodium is also associated with adverse outcomes. Novel techniques, based on time-dependent analysis of variability and trends and interactions of multiple physiological and laboratory parameters, for which machine-learning -approaches may be necessary, are likely of help to the clinician in the future. However, upcoming research should also evaluate whether dynamic patterns observed in large epidemiological studies have relevance for the individual risk profile of the patient.

Rasha Hussein, Ana Catalina Alvarez-Elías, Alice Topping, Jochen G Raimann, Guido Filler, Dalia Yousif, Peter Kotanko, Len A Usvyat, Mara Medeiros, Roberto Pecoits-Filho, Bernard Canaud, Stefano Stuard, Xu Xiaoqi, Michael Etter, Maria E Díaz-González de Ferris

RESULTSThe patients' median age was 16 (IQR 14-17) years, and 45% were females. A height z score less than the third percentile was noted in 34% of the cohort, whereas >66% of patients reported normal heights, with patients from North America having the greatest proportion (>80%). More than 70% of the entire cohort had greater than the age-recommended levels of phosphorus, particularly in the Asia-Pacific and North America, where we also observed the greatest body mass index z score (0.99 ± 1.6) and parathyroid hormone levels (557.1 [268.4-740.5]). Below-recommended parathyroid hormone levels were noted in 26% and elevated levels in 61% of the entire sample, particularly in the Asia Pacific region. Lower-than-recommended calcium levels were noted in 36% of the entire cohort, particularly in Latin America.CONCLUSIONSWe found regional differences in growth- and age-adjusted bone mineral metabolism markers. Children from North America had the best growth, received the most dialysis, but also had the worst phosphate control and body mass index z scores.STUDY DESIGNIn this cross-sectional study, we analyzed growth by height z score and recommended age-specific bone mineral metabolism markers from 225 patients <18 years of age maintained on hemodialysis, between the years of 2000 to 2012 from 21 countries in different regions.OBJECTIVEWe sought to assess worldwide differences among pediatric patients undergoing hemodialysis. Because practices differ widely regarding nutritional resources, treatment practice, and access to renal replacement therapy, investigators from the Pediatric Investigation and Close Collaboration to examine Ongoing Life Outcomes, the pediatric subset of the MONitoring Dialysis Outcomes Cohort (PICCOLO MONDO) performed this cross-sectional study. We hypothesized that growth would be better in developed countries, possibly at the expense of bone mineral disease.

Jennifer E Flythe, Adeline Dorough, Julia H Narendra, Rebecca L Wingard, Lorien S Dalrymple, Darren A DeWalt

RESULTSForty-two adults receiving in-center hemodialysis participated in the concept elicitation interviews. A total of 12 symptoms were reported by > 10% of interviewees. We developed a 13-item initial draft instrument for testing in 3 rounds of cognitive interviews with an additional 52 hemodialysis patients. Participant responses and feedback during cognitive interviews led to changes in symptom descriptions, division of the single item "nausea/vomiting" into 2 distinct items, removal of daily activity interference items, addition of instructions, and clarification about the recall period, among other changes.CONCLUSIONSSymptom Monitoring on Renal Replacement Therapy-Hemodialysis (SMaRRT-HD™) is a 14-item PROM intended for use in hemodialysis patents. SMaRRT-HD™ uses a single treatment recall period and a 5-point Likert scale to assess symptom severity. Qualitative interview data provide evidence of its content validity. SMaRRT-HD™ is undergoing additional testing to assess measurement properties and inform measure scoring.PURPOSETo describe the process and preliminary qualitative development of a new symptom-based patient-reported outcome measure (PROM) intended to assess hemodialysis treatment-related physical symptoms.METHODSExperienced interviewers conducted concept elicitation and cognitive debriefing interviews with individuals receiving in-center hemodialysis in the United States. Concept elicitation interviews involved eliciting spontaneous reports of symptom experiences and probing to further explore and confirm concepts. We used patient-reported concepts to generate a preliminary symptom PROM. We conducted 3 rounds of cognitive debriefing interviews to evaluate symptom relevance, item interpretability, and draft item structure. We iteratively refined the measure based on cognitive interview findings.

Marijke J E Dekker, Constantijn Konings, Bernard Canaud, Frank M van der Sande, Stefano Stuard, Jochen G Raimann, Elife Öztürk, Len Usvyat, Peter Kotanko, Jeroen P Kooman

RESULTSThe presence of malnutrition was associated with higher levels of FO, this amount further increased when inflammation was present. Only 11.6% of the patients did not have any of the 3 risk factors and only 6.5% of the patients were only malnourished, which was not associated with an increased risk of death (Hazard Ratio [HR] 1.22 [95% Confidence Interval [CI]: 0.75-1.97]), whereas the combination of severe malnutrition, FO, and inflammation comprised the highest risk of death (HR 5.89 [95% CI: 2.28-8.01]).SUBJECTS8883 prevalent HD patients.MAIN OUTCOME MEASUREBody composition, nutritional and inflammation status were assessed during a 3-month baseline period, and all-cause mortality was noted during 1 year follow-up. Malnutrition was defined as a lean tissue index <10th percentile (of age and gender matched healthy controls), FO as a predialysis overhydration >+1.1 L and inflammation as a C-reactive protein > 6.0 mg/L. We used Cox models to investigate the association with outcome.DESIGNInternational cohort study.OBJECTIVEPredialysis fluid overload (FO) in hemodialysis (HD) patients is associated with an increased risk of death, further increased by the presence of inflammation. Malnutrition is also associated with outcome. Study objectives were, firstly, to investigate if the presence of FO is associated with malnutrition and whether this association is influenced by the presence of inflammation. Second, we assessed the associations of FO, malnutrition, and inflammation with outcome individually and in combination.CONCLUSIONIn HD patients, predialysis FO associates with both malnutrition and the presence of inflammation, with the highest levels of FO observed when both are present. Malnutrition as singular risk factor was not associated with increased mortality risk. The highest mortality risk was observed in patients where all 3 risk factors were present.SETTINGEuropean patients of the Monitoring Dialysis Outcome Initiative cohort where bioimpedance and C-reactive protein measurements are performed as standard of care.

George A Kaysen, Xiaoling Ye, Jochen G Raimann, Yuedong Wang, Alice Topping, Len A Usvyat, Stefano Stuard, Bernard Canaud, Frank M van der Sande, Jeroen P Kooman, Peter Kotanko

Cardiovascular (CV) events are increased 36-fold in patients with end-stage renal disease. However, randomized controlled trials to lower LDL cholesterol (LDL-C) and serum total cholesterol (TC) have not shown significant mortality improvements. An inverse association of TC and LDL-C with all-cause and CV mortality has been observed in patients on chronic dialysis. Lipoproteins also may protect against infectious diseases. We used data from 37,250 patients in the international Monitoring Dialysis Outcomes (MONDO) database to evaluate the association between lipids and infection-related or CV mortality. The study began on the first day of lipid measurement and continued for up to 4 years. We applied Cox proportional models with time-varying covariates to study associations of LDL-C, HDL cholesterol (HDL-C), and triglycerides (TGs) with all-cause, CV, infectious, and other causes of death. Overall, 6,147 patients died (19.2% from CV, 13.2% from infection, and 67.6% from other causes). After multivariable adjustment, higher LDL-C, HDL-C, and TGs were independently associated with lower all-cause death risk. Neither LDL-C nor TGs were associated with CV death, and HDL-C was associated with lower CV risk. Higher LDL-C and HDL-C were associated with a lower risk of death from infection or other non-CV causes. LDL-C was associated with reduced all-cause and infectious, but not CV mortality, which resulted in the inverse association with all-cause mortality.

Doris H Fuertinger, Franz Kappel, Hanjie Zhang, Stephan Thijssen, Peter Kotanko

Anemia commonly occurs in people with chronic kidney disease (CKD) and is associated with poor clinical outcomes. The management of patients with anemia in CKD is challenging, due to its severity, frequent hypo-responsiveness to treatment with erythropoiesis stimulating agents (ESA) and common hemoglobin cycling. Nonlinear dose-response curves and long delays in the effect of treatment on red blood cell population size complicate predictions of hemoglobin (Hgb) levels in individual patients. A comprehensive physiology based mathematical model for erythropoiesis was adapted individually to 60 hemodialysis patients treated with ESAs by identifying physiologically meaningful key model parameters from temporal Hgb data. Crit-Line® III monitors provided non-invasive Hgb measurements for every hemodialysis treatment. We used Hgb data during a 150-day baseline period together to estimate a patient's individual red blood cell lifespan, effects of the ESA on proliferation of red cell progenitor cells, endogenous erythropoietin production and ESA half-life. Estimated patient specific parameters showed excellent alignment with previously conducted clinical studies in hemodialysis patients. Further, the model qualitatively and quantitatively reflected empirical hemoglobin dynamics in demographically, anthropometrically and clinically diverse patients and accurately predicted the Hgb response to ESA therapy in individual patients for up to 21 weeks. The findings suggest that estimated model parameters can be used as a proxy for parameters that are clinically very difficult to quantify. The presented method has the potential to provide new insights into the individual pathophysiology of renal anemia and its association with clinical outcomes and can potentially be used to guide personalized anemia treatment.

Samir Patel, Alice Topping, Xiaoling Ye, Hanjie Zhang, Bernard Canaud, Paola Carioni, Cristina Marelli, Adrian Guinsburg, Albert Power, Neill Duncan, Jeroen Kooman, Frank van der Sande, Len A Usvyat, Yuedong Wang, Xiaoqi Xu, Peter Kotanko, Jochen G Raimann

RESULTSWe studied 23,353 patients (62 ± 15 years old, 42% female, body mass index 26 ± 6 kg/m2, height 165 ± 10 cm). We found a trend of increasing hazard ratio of death (HR) with increasing height for Asia Pacific, Europe, and South America. In the fully adjusted models, for South America, we found a trend of increasing HR without significance among deciles >5. In Europe, deciles 8-10 had significantly increased HR. No clear trend was found in North America.CONCLUSIONWe found an increasing risk of death with increasing height in all regions, except North America. While the reasons remain unclear, further research may be warranted.BACKGROUNDTall people have improved metabolic profiles and better cardiovascular outcomes, a relationship inverted in dialysis patients. We investigated the relationship between height and outcomes in incident hemodialysis (HD) patients commencing treatment in an analysis of the international Monitoring Dialysis Outcomes (MONDO) database.METHODSIn this retrospective cohort study, we included incident HD patients commencing treatment between -January 1, 2006 and December 31, 2010 and investigated the association between height and mortality using the MONDO database. A 6-months baseline period preceded 2.5 years of follow-up, during which we recorded patient mortality. Patients were stratified in region-specific deciles of the respective database's population (Asia Pacific, North and South America, and Europe) and we developed Cox-proportional hazard models (additionally adjusted for age, gender, post-dialysis weight, eKt/V, albumin, interdialytic weight gain, phosphorus, and predialysis systolic blood pressure) for each database.

Shakil Aslam, Subodh J Saggi, Moro Salifu, Robert J Kossmann

Dialysis dose is an important determinant of clinical outcomes in patients with end stage renal disease on maintenance dialysis. In clinical practice dialysis dose is monitored at least monthly by urea clearance based on Urea Kinetic Modeling. Online clearance monitoring using effective ionic dialysance (EID) of sodium (Na+ ) is available on some hemodialysis machines. This paper reviews the background, methodology, additional applications, and potential risks associated with EID. Effective ionic dialysance provides a reliable, real-time, noninvasive, and inexpensive measurement of dialysis dose during an ongoing hemodialysis (HD) session to allow interventions and assess the impact of these changes on clearance. Surveillance of vascular access flow rates can be used to screen for access dysfunction and refer for interventions. There is a concern that EID measurements may cause Na+ loading because of high dialysate Na+ used during these measurements, however, mathematical models, in vitro experiments, and clinical studies in patients on maintenance HD do not show any evidence of Na+ loading during EID measurements. We cannot rule out the possibility of nonosmotic Na+ accumulation in the skin because no published literature exists on this topic as it pertains to clearance measurements based on EID of Na+ .

Xiaoling Ye, Marijke J E Dekker, Franklin W Maddux, Peter Kotanko, Constantijn J A M Konings, Jochen G Raimann, Frank M van der Sande, Len A Usvyat, Jeroen P Kooman, Stephan Thijssen

OBJECTIVESRecently, a new Nutritional Competence Score (NCS) has been shown to associate with hospitalization and outcome in hemodialysis patients. The aim of this study was to investigate the dynamics, the individual components, and the impact of hospitalizations of this score's trajectory in the year before death. In addition, we investigated whether dynamics in the NCS add additional independent prognostic value over a single cross-sectional assessment.RESULTSIn this cohort of 110,794 patients, we found that across all vintage groups, NCS was lower in patients who died than in survivors. NCS was found to significantly decline before death, whereas survivors showed no decline in NCS. The rate of NCS decline before death was not materially influenced by hospitalization in the months before death. Cox models showed that NCS dynamics over time carry significant predictive power above a cross-sectional NCS assessment.DESIGNWe included all Fresenius Medical Care North America patients who initiated hemodialysis between January 1, 2006, and December 31, 2011 with data on all 5 NCS components (serum albumin, creatinine, phosphate, equilibrated normalized protein catabolic rate, and interdialytic weight gain) in at least 1 month. NCS was quantified monthly, and trajectories were compared between nonsurvivors and survivors across different dialysis vintage strata. Survivors and nonsurvivors were matched by dialysis vintage. The association of baseline NCS and NCS dynamics with mortality risk were assessed with Cox proportional hazards models.CONCLUSIONSThere are distinct differences in NCS values and their trajectories between patients who die and vintage-matched controls. These differences may be able to be exploited for implementation of a routine, prospective monitoring tool for early detection of patients at increased risk of death. Prospective studies are required to validate such an approach.

Lili Chan, Hanjie Zhang, Anna Meyring-Wösten, Israel Campos, Doris Fuertinger, Stephan Thijssen, Peter Kotanko

Central venous oxygen saturation (ScvO2) in the superior vena cava is predominantly determined by cardiac output, arterial oxygen content, and oxygen consumption by the upper body. While abnormal ScvO2 levels are associated with morbidity and mortality in non-uremic populations, ScvO2 has received little attention in hemodialysis patients. From 1/2012 to 8/2015, 232 chronic hemodialysis patients with central venous catheters as vascular access had their ScvO2 monitored during a 6-month baseline period and followed for up to 36 months. Patients were stratified into upper and lower two tertiles by a ScvO2 of 61.1%. Survival analysis employed Kaplan-Meier curves and adjusted Cox proportional hazards models. Patients in the lower tertiles of ScvO2 were older, had longer hemodialysis vintage, lower systolic blood pressure, lower ultrafiltration rates, higher leukocyte counts and neutrophil-to-lymphocyte ratios. Kaplan-Meier analysis indicated a shorter survival time in the lower tertiles of ScvO2 (P = 0.005, log-rank test). In adjusted Cox analysis, a 1 percent point decrease in mean ScvO2 was associated with a 4% increase in mortality (HR 1.04 [95% CI 1.01-1.08], P = 0.044), indicating that low ScvO2 is associated with poor outcomes. Research on the relative contributions of cardiac output and other factors is warranted to further elucidate the pathophysiology underlying this novel finding.

Jochen G Raimann, Claudia Barth, Len A Usvyat, Priscila Preciado, Bernard Canaud, Michael Etter, Xiaoqi Xu, Adrian Guinsburg, Christina Marelli, Neill Duncan, Albert Power, Frank M van der Sande, Jeroen P Kooman, Stephan Thijssen, Yuedong Wang, Peter Kotanko

RESULTSIn 14,966 elderly, incident HD patients, survival was significantly worse when using a CVC at all times. In Europe, the conversion frequency from CVC to non-CVC was higher in the younger fraction. Conversion from non-CVC to CVC was associated with worsened outcomes only in the older fraction.CONCLUSIONThese results corroborate the need for early HD preparation in the elderly HD population. Treatment of elderly patients who commence HD with a CVC should be planned considering aspects of individual clinical risk assessment. Differences in treatment practices in predialysis care specific to the elderly as a population may influence access care and conversion rate.BACKGROUNDCommencing hemodialysis (HD) using a catheter is associated with a higher risk of adverse outcomes, and early conversion from central-venous catheter (CVC) to arteriovenous fistula/graft (non-CVC) improves outcomes. We investigated CVC prevalence and conversion, and their effects on outcomes during the first year of HD in a multinational cohort of elderly patients.METHODSPatients ≥70 years from the MONDO Initiative who commenced HD between 2000 and 2010 in Asia-Pacific, Europe, North-, and South-America and survived at least 6 months were included in this investigation. We stratified by age (70-79 years [younger] vs. ≥80 years [older]) and compared access types (at first and last available date) and their changes. We studied the association between access at initiation and conversion, respectively, and all-cause mortality using Kaplan-Meier curve and Cox regression, and predicted the absence of conversion from catheter to non-CVC using adjusted logistic regression.

Carmine Zoccali, Ulrich Moissl, Charles Chazot, Francesca Mallamaci, Giovanni Tripepi, Otto Arkossy, Peter Wabel, Stefano Stuard

Sustained fluid overload (FO) is considered a major cause of hypertension, heart failure, and mortality in patients with ESRD on maintenance hemodialysis. However, there has not been a cohort study investigating the relationship between chronic exposure to FO and mortality in this population. We studied the relationship of baseline and cumulative FO exposure over 1 year with mortality in 39,566 patients with incident ESRD in a large dialysis network in 26 countries using whole-body bioimpedance spectroscopy to assess fluid status. Analyses were applied across three discrete systolic BP (syst-BP) categories (<130, 130-160, and >160 mmHg), with nonoverhydrated patients with syst-BP=130-160 mmHg as the reference category; >200,000 FO measurements were performed over follow-up. Baseline FO value predicted excess risk of mortality across syst-BP categories (<130 mmHg: hazard ratio [HR], 1.51; 95% confidence interval [95% CI], 1.38 to 1.65; 130-160 mmHg: HR, 1.25; 95% CI, 1.16 to 1.36; >160 mmHg: HR, 1.30; 95% CI, 1.19 to 1.42; all P<0.001). However, cumulative 1-year FO exposure predicted a higher death risk (P<0.001) across all syst-BP categories (<130 mmHg: HR, 1.94; 95% CI, 1.68 to 2.23; 130-160 mmHg: HR, 1.51; 95% CI, 1.35 to 1.69; >160 mmHg: HR, 1.62; 95% CI, 1.39 to 1.90). In conclusion, chronic exposure to FO in ESRD is a strong risk factor for death across discrete BP categories. Whether treatment policies that account for fluid status monitoring are preferable to policies that account solely for predialysis BP measurements remains to be tested in a clinical trial.

Marijke J E Dekker, Daniele Marcelli, Bernard J Canaud, Paola Carioni, Yuedong Wang, Aileen Grassmann, Constantijn J A M Konings, Peter Kotanko, Karel M Leunissen, Nathan W Levin, Frank M van der Sande, Xiaoling Ye, Vaibhav Maheshwari, Len A Usvyat, Jeroen P Kooman

In hemodialysis patients extracellular fluid overload is a predictor of all-cause and cardiovascular mortality, and a relation with inflammation has been reported in previous studies. The magnitude and nature of this interaction and the effects of moderate fluid overload and extracellular fluid depletion on survival are still unclear. We present the results of an international cohort study in 8883 hemodialysis patients from the European MONDO initiative database where, during a three-month baseline period, fluid status was assessed using bioimpedance and inflammation by C-reactive protein. All-cause mortality was recorded during 12 months of follow up. In a second analysis a three-month baseline period was added to the first baseline period, and changes in fluid and inflammation status were related to all-cause mortality during six-month follow up. Both pre-dialysis estimated fluid overload and fluid depletion were associated with an increased mortality, already apparent at moderate levels of estimated pre-dialysis fluid overload (1.1-2.5L); hazard ratio 1.64 (95% confidence interval 1.35-1.98). In contrast, post-dialysis estimated fluid depletion was associated with a survival benefit (0.74 [0.62-0.90]). The concurrent presence of fluid overload and inflammation was associated with the highest risk of death. Thus, while pre-dialysis fluid overload was associated with inflammation, even in the absence of inflammation, fluid overload remained a significant risk factor for short-term mortality, even following improvement of fluid status.

Paik Seong Lim, Chang Hsu Chen, Fansan Zhu, Peter Kotanko, Yachung Jeng, Chun Yu Hu, Li Shu Chiu, Hui-Chen Chang

RESULTSAssessment of whole-body composition showed that percentage FM measured using the 2 techniques was highly correlated when using the BCM model or estimating from total body water using constant (0.73) hydration (r = 0.87, P < .001). There was no evident difference in measurement between patients gender. The Bland-Altman plot also showed good agreement of percentage of FM (t = 3.82; P < .001). In female patients, it was found that BCM significantly underestimated mean FM as compared to DEXA. However, the mean differences of the estimates between the methods were small (0.35 ± 3.00 kg) and with Bland-Altman plot the limits of agreements were -5.5 to 6.2 kg (P = .40) for FM in female patients.SUBJECTSOne hundred twenty-two adult patients receiving HD in a single hospital in Taiwan.DESIGNCross-sectional study.CONCLUSIONSUsing DEXA as the reference test, BCM is a valid tool for the assessment of total body fat in HD patients. Hence, it may provide a more accessible tool for early detection of changes in body composition in these high-risk patients.OBJECTIVEObesity is becoming increasingly common in hemodialysis (HD) patients and is associated with inflammation and increased mortality. The primary aim of the present study was to evaluate the accuracy and variability of the bioimpedance device in measuring body fat in Taiwanese dialysis patients.SETTINGWe compared the results of fat mass (FM) measured by dual-energy x-ray absorptiometry (DEXA) and bioelectrical impedance spectroscopy device (Body composition monitor, BCM).MAIN OUTCOME MEASUREMENTFM measured by BCM was calculated by subtracting fat-free mass (FFM) from body mass assuming fractional hydration of FFM of 0.73 or the proprietary prediction equations from the BCM model.

Jochen G Raimann, Antonios H Tzamaloukas, Nathan W Levin, Todd S Ing

Since the beginning of life of the first multicellular organisms, the preservation of a physiologic milieu for every cell in the organism has been a critical requirement. A particular range of osmolality of the body fluids is essential for the maintenance of cell volume. In humans the stability of electrolyte concentrations and their resulting osmolality in the body fluids is the consequence of complex interactions between cell membrane functions, hormonal control, thirst, and controlled kidney excretion of fluid and solutes. Knowledge of these mechanisms, of the biochemical principles of osmolality, and of the relevant situations occurring in disease is of importance to every physician. This comprehensive review summarizes the major facts on osmolality, its relation to electrolytes and other solutes, and its relevance in physiology and in disease states with a focus on dialysis-related considerations.

Cécile Couchoud, Brenda Hemmelgarn, Peter Kotanko, Michael J Germain, Olivier Moranne, Sara N Davison

In using a patient-centered approach, neither a clinician nor a prognostic score can predict with absolute certainty how well a patient will do or how long he will live; however, validated prognostic scores may improve accuracy of prognostic estimates, thereby enhancing the ability of the clinicians to appreciate the individual burden of disease and the prognosis of their patients and inform them accordingly. They may also facilitate nephrologist's recommendation of dialysis services to those who may benefit and proposal of alternative care pathways that might better respect patients' values and goals to those who are unlikely to benefit. The purpose of this article is to discuss the use as well as the limits and deficiencies of currently available prognostic tools. It will describe new predictors that could be integrated in future scores and the role of patients' priorities in development of new scores. Delivering patient-centered care requires an understanding of patients' priorities that are important and relevant to them. Because of limits of available scores, the contribution of new prognostic tools with specific markers of the trajectories for patients with CKD and patients' health reports should be evaluated in relation to their transportability to different clinical and cultural contexts and their potential for integration into the decision-making processes. The benefit of their use then needs to be quantified in clinical practice by outcome studies including health-related quality of life, patient and caregiver satisfaction, or utility for improving clinical management pathways and tailoring individualized patient-centered strategies of care. Future research also needs to incorporate qualitative methods involving patients and their caregivers to better understand the barriers and facilitators to use of these tools in the clinical setting. Information given to patients should be supported by a more realistic approach to what dialysis is likely to entail for the individual patient in terms of likely quality and quantity of life according to the patient's values and goals and not just the possibility of life prolongation.

M J E Dekker, D Marcelli, B Canaud, C J A M Konings, K M Leunissen, N W Levin, P Carioni, V Maheshwari, J G Raimann, F M van der Sande, L A Usvyat, P Kotanko, J P Kooman

RESULTSHyponatremia was predicted by the presence of malnutrition (odds ratio (OR)=1.49 (95% confidence interval (CI)=1.30-1.70), inflammation (OR=1.44 (95% CI=1.26-1.64)) and fluid overload ((>+1.1 l to +2.5 l) OR=0.73 (95% CI=0.62-0.85)) but not by fluid depletion (OR=1.34 (95% CI=0.92-1.96)). Malnutrition, inflammation, fluid overload, fluid depletion and hyponatremia (hazard ratio=1.70 (95% CI=1.46-1.99)) were independent predictors for all-cause mortality.CONCLUSIONSIn HD patients, hyponatremia is associated with malnutrition, inflammation and fluid overload. Hyponatremia maintained predictive for all-cause mortality after adjustment for malnutrition, inflammation and fluid status abnormalities. The presence of hyponatremia may assist in identifying HD patients at increased risk of death.BACKGROUND/OBJECTIVESHyponatremia is a risk factor for mortality in hemodialysis (HD) patients. It is not well known to which extent the comorbidities, malnutrition, fluid status imbalance and inflammation are related to hyponatremia and affect outcomes.SUBJECTS/METHODSWe studied 8883 patients from the European subset of the international MONitoring Dialysis Outcomes initiative. Nutritional and fluid statuses were assessed by bioimpedance spectroscopy. Fluid depletion was defined as overhydration⩽-1.1 l and fluid overload as overhydration>+1.1 l, respectively. Malnutrition was defined as a lean tissue index below the 10th percentile of age- and gender-matched healthy controls. Hyponatremia and inflammation were defined as serum sodium levels <135 mEq/l and C-reactive protein levels>6.0 mg/l, respectively. We used logistic regression to test for predictors of hyponatremia and Cox proportional hazards analysis to assess the association with all-cause mortality.

Maria Ferris, Keisha Gibson, Brett Plattner, Debbie S Gipson, Peter Kotanko, Daniele Marcelli, Cristina Marelli, Michael Etter, Paola Carioni, Gero von Gersdorff, Xiaoqi Xu, Jeroen P Kooman, Qingqing Xiao, Frank M van der Sande, Albert Power, Roberto Picoits-Filho, Lucimary Sylvestre, Katherine Westreich, Len Usvyat

RESULTSFor those with known end-stage renal disease etiology, glomerular disease was the most common diagnosis in children and young adults. Using Europe as a reference group, North America [odds ratio (OR) 2.69; CI 1.29, 5.63] and South America (OR 4.21; CI 2.32, 7.63) had the greatest mortality among young adults. North America also had higher rates of overweight, obesity, hypertension, cardiovascular disease, hospitalizations and secondary diabetes compared with all other regions. Initial catheter use was greater for North American (86.4% in pediatric patients and 75.2% in young adults) and South America (80.6% in pediatric patients and 75.9% in young adults). Catheter use at 1-year follow-up was most common in North American children (77.3%) and young adults (62.9%). Asia had the lowest rate of catheter use. For both age groups, dialysis adequacy (equilibrated Kt/V) ranged between 1.4 and 1.5. In Asia, patients in both age groups had significantly longer treatment times than in any other region.CONCLUSIONSThe PICCOLO MONDO study has provided unique baseline and 1-year follow-up information on children and young adults receiving HD around the globe. This cohort has brought to light aspects of care in these age groups that warrant further investigation.BACKGROUNDThe aim of this study was to describe the experience of pediatric and young adult hemodialysis (HD) patients from a global cohort.METHODSThe Pediatric Investigation and Close Collaborative Consortium for Ongoing Life Outcomes for MONitoring Dialysis Outcomes (PICCOLO MONDO) study provided de-identified electronic information of 3244 patients, ages 0-30 years from 2000 to 2012 in four regions: Asia, Europe, North America and South America. The study sample was categorized into pediatric (≤18 years old) and young adult (19-30 years old) groups based on the age at dialysis initiation.

Hilde R H de Geus, Claudio Ronco, Michael Haase, Laurent Jacob, Andrew Lewington, Jean-Louis Vincent

Acute kidney injury (AKI), defined as a rise in serum creatinine (functional AKI), is a frequent complication after cardiac surgery. The expression pattern of acute tubular damage biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) has been shown to precede functional AKI and, therefore, may be useful to identify very early tubular damage. The term subclinical AKI represents acute tubular damage in the absence of functional AKI (biomarker positivity without a rise in serum creatinine) and affects hard outcome measures. This potentiates an tubular-damage-based identification of renal injury, which may guide clinical management, allowing for very early preventive-protective strategies. The aim of this paper was to review the current available evidence on NGAL applicability in adult cardiac surgery patients and combine this knowledge with the expert consensus of the authors to generate an NGAL based tubular damage score: The cardiac surgery-associated NGAL Score (CSA-NGAL score). The CSA-NGAL score might be the tool needed to improve awareness and enable interventions to possibly modify these detrimental outcomes. In boldly doing so, it is intended to introduce a different approach in study designs, which will undoubtedly expand our knowledge and will hopefully move the AKI biomarker field forward.

Adrian M Guinsburg, Len A Usvyat, Michael Etter, Xiaoqi Xu, Stephan Thijssen, Daniele Marcelli, Bernard Canaud, Cristina Marelli, Claudia Barth, Yuedong Wang, Paola Carioni, Frank M van der Sande, Peter Kotanko, Jeroen P Kooman

RESULTSData from 87,399 patients were included (northern temperate: 63,671; northern tropical: 7,159; southern temperate: 13,917; southern tropical: 2,652 patients). Globally, mortality was highest in winter. Following stratification, mortality was significantly lower in spring and summer compared to winter in temperate, but not in tropical zones. Globally, pre-SBP and IDWG were lower in summer and spring as compared to winter, although less pronounced in tropical zones. Except for southern temperate zone, serum albumin levels were higher in winter. CRP levels were highest in winter.CONCLUSIONSignificant global seasonal variations in mortality, pre-SBP, IDWG, albumin and CRP were observed. Seasonal variations in mortality were most pronounced in temperate climate zones.BACKGROUNDSeasonal mortality differences have been reported in US hemodialysis (HD) patients. Here we examine the effect of seasons on mortality, clinical and laboratory parameters on a global scale.METHODSDatabases from the international Monitoring Dialysis Outcomes (MONDO) consortium were queried to identify patients who received in-center HD for at least 1 year. Clinics were stratified by hemisphere and climate zone (tropical or temperate). We recorded mortality and computed averages of pre-dialysis systolic blood pressure (pre-SBP), interdialytic weight gain (IDWG), serum albumin, and log C-reactive protein (CRP). We explored seasonal effects using cosinor analysis and adjusted linear mixed models globally, and after stratification.

J G Raimann, B Canaud, M Etter, J P Kooman, N W Levin, D Marcelli, C Marelli, A Power, N Duncan, F M van der Sande, P Carioni, S Thijssen, X Xu, L A Usvyat, Y Wang, P Kotanko

A recent study from the United Kingdom indicates an association between pre hemodialysis (HD) serum sodium (SNa(+)) and systolic and diastolic blood pressure (SBP and DBP) in chronic HD patients. We extend this analysis to an international cohort of incident HD patients. The Monitoring Dialysis Outcomes initiative encompasses patients from 41 countries. Over 2 years monthly pre-HD SNa(+) levels were used as predictors of pre-HD SBP and DBP in a linear mixed model (LMM) adjusted for age, gender, interdialytic weight gain, diabetes, serum albumin and calcium. Similar models were constructed with DBP as outcome. Analyses were carried out stratified by continent (North and South America; Europe and Asia). LMMs were also constructed for the entire observation period of 2 years, and separately the first and the second year after HD initiation. We studied 17 050 incident patients and found SNa(+) to have a significant slope estimate in the LMM predicting pre-HD SBP and DBP (ranging from 0.22 to 0.29 and 0.10 to 0.21 mm Hg per mEq l(-1), respectively, between the continents). The findings were similar in subsets of SBP and SNa(+) tertiles, and separately analyzed for the first and second year. Our analysis shows an independent association between SNa, SBP and DBP in a large intercontinental database, indicating that this relation is a profound biological phenomenon in incident and prevalent HD patients, generalizable to an international level and independent of SBP and DBP magnitude.

Rakesh Malhotra, Daniele Marcelli, Gero von Gersdorff, Aileen Grassmann, Mathias Schaller, Inga Bayh, Laura Scatizzi, Michael Etter, Adrian Guinsburg, Claudia Barth, Cristina Marelli, Paola Carioni, Frank van der Sande, Jeroen P Kooman, Eric Liu, Ted Toffelmire, Yuedong Wang, Stephan Thijssen, Len A Usvyat, Peter Kotanko

RESULTSWe found that NLR >5.0 vs. <2.5 (cohort 1: OR 2.3; p < 0.0001 and cohort 2: OR 2.0; p < 0.0001) was associated with CRP levels >10.0 mg/l. Stepwise increase in odds ratio for CRP >10.0 mg/l was observed with the combination of high NLR and low albumin levels (NLR >5.0 and albumin <3.1) (cohort 1: OR 7.6; p < 0.0001 and cohort 2: OR 11.9; p < 0.0001). Cross-validation of the 2 regression models revealed a predictive accuracy of 0.68 and 0.69 in the respective cohorts.CONCLUSIONThis study suggests that NLR could serve as a potential surrogate marker for CRP. Our results may add to diagnostic abilities in settings where CRP is not measured routinely in HD patients. NLR is easy to integrate into daily practice and may be used as a marker of systemic inflammation.BACKGROUND/AIMThe neutrophil-to-lymphocyte ratio (NLR), defined as the neutrophil count divided by lymphocyte count, is an inexpensive and readily available parameter, which may serve as a surrogate for inflammation markers, such as C-reactive protein (CRP). The aim of this study was to determine the utility of NLR in the prediction of elevated CRP levels in hemodialysis (HD) patients.METHODSWe analyzed 43,272 HD patients from 2 distinct cohorts within the Monitoring Dialysis Outcomes research collaboration in whom contemporaneous measurements of neutrophil and lymphocyte counts, serum albumin and CRP levels were available. Logistic regression was used to determine the relationship of trichotomized NLR (<2.5, 2.5-5 and >5.0) and albumin levels (<3.1, 3.1-4.0 and >4.0 g/dl) with elevated CRP levels (>10.0, >20.0 and >30.0 mg/l). Congruence of the prediction models was examined by comparing the regression parameters and by cross-validating each regression equation within the other cohort.

Paul Balter, Linda H Ficociello, Patrice B Taylor, Len Usvyat, Dixie-Ann Sawin, Claudy Mullon, Jose Diaz-Buxo, Paul Zabetakis

RESULTSAverage hemodialysis treatment time (+10.6 minutes, p = 0.002), eKt/V (+0.25, p < 0.001) and online clearance (+0.21, p < 0.0001) increased significantly in Month 12 versus Month 1. Average albumin levels and normalized protein catabolic rate increased from Month 1 to 12. Post-dialysis systolic blood pressure (SBP) decreased by Month 12 (p = 0.003). In hypertensive patients (SBP ≥ 140 mmHg in Month 1), there were significant differences in pre- and post-dialysis SBP between Month 1 and Month 12 (pre-hemodialysis: p = 0.02; post-hemodialysis: p = 0.0003), and antihypertensive medication use decreased in 29% of patients, while only 11% increased use. Treatment time in hypertensive patients increased by 15.4 minutes (p = 0.0005).CONCLUSIONSDuring this year-long fluid management quality improvement project, decreases in post-dialysis SBP and increases in adequacy and treatment time were observed. Patients with hypertension at Month 1 experienced reductions in pre-dialysis SBP and antihypertensive medications.LIMITATIONSThis was a single, clinic-wide, quality improvement project with no control group. All data analyzed were from existing clinical records, so only routinely measured clinical variables were available and missing data were possible.BACKGROUNDInadequate removal of extracellular volume markedly increases blood pressure and contributes to high morbidity and mortality in hemodialysis patients. Advances in fluid management are needed to improve clinical outcomes. The aim of this quality improvement project was to examine the advantages of using a hematocrit-based, blood volume monitor (Crit-Line * ) for 12 months, as part of a clinic-wide, fluid management program in one dialysis facility.METHODSForty-five individuals were receiving hemodialysis at one facility at project initiation and are included in this analysis. Monthly averaged clinical parameters (dialysis treatment information, blood pressures, blood volume, and laboratory data) were compared from Months 1-12. Analyses were conducted overall and according to the presence/absence of hypertension at Month 1 (Baseline). Antihypertensive medication changes were assessed for patients with hypertension at Month 1.

Grazia Maria Virzì, Sabrina Milan Manani, Alessandra Brocca, Vincenzo Cantaluppi, Massimo de Cal, Silvia Pastori, Ilaria Tantillo, Roberto Zambon, Carlo Crepaldi, Claudio Ronco

RESULTSQuantitative analysis of cfDNA showed significantly higher levels in group B on day 1, 3, 10 and 30 compared with group A (p < 0.05). A significant positive correlation was observed between cfDNA concentration and WBC on day 1 (rho = 0.89) and day 3 (rho = 0.5) (both, p < 0.05). However, no significant correlation was observed between cfDNA and WBC on days 10 and 30. In group B, peritoneal cfDNA levels tended to progressively decline during follow-up of peritonitis. From this decreasing curve, we estimated that 49 days are necessary to reach the value of 51 genome equivalents (GE)/ml (75th percentile in controls) and 63 days to reach 31 GE/ml (median).CONCLUSIONOur results demonstrate that cfDNA increases in peritoneal effluent of PD patients with peritonitis and tends to progressively decline in step with peritonitis resolution and membrane repair process. Peritoneal cfDNA quantification could be an innovative method to determine acute damage and an inverse index of the repair process.BACKGROUNDCell-free DNA (cfDNA) is present in the peritoneal effluent of stable peritoneal dialysis (PD) patients, but there are no data on cfDNA in PD patients with peritonitis. We investigated the variation of peritoneal cfDNA levels subsequent to peritonitis in PD patients.METHODSWe enrolled 53 PD patients: 30 without any history of systemic inflammation or peritonitis in the last 3 months (group A) and 23 with acute peritonitis (group B). CfDNA was quantified in the peritoneal effluent. Peritoneal samples on days 1, 3, 10, 30 and until day 120 from the start of peritonitis were collected for white blood cells (WBC) count and cfDNA evaluation in group B.

Claudio Ronco, Zaccaria Ricci, Stuart L Goldstein

The application of continuous renal replacement therapy (CRRT) in children, before roller pumps and dialysis monitors were available in the intensive care unit, was realized by continuous arteriovenous hemofiltration. Then hemofiltration was coupled with dialysis in order to increase dialytic dose and system efficiency, and the circuit and filters were specifically modified to optimize patency and session life span. After about 30 years, another revolution is ongoing, in that pediatric acute kidney injury (AKI) and fluid accumulation (for which critically ill newborns and children with multiple-organ dysfunction are greatly at risk) are recognized as independently associated with mortality and identified as primary conditions to prevent and aggressively treat. Today, novel technology specifically dedicated for very young patients will allow feasible and straightfoward application of CRRT to infants and children. This article discusses the authors' personal perspectives on how clinical and technical issues of dialysis in children have been addressed and how today, severe pediatric AKI can be managed with accurate and safe CRRT machines that will likely yield outcome improvements in the coming decades.

Daniele Marcelli, Len A Usvyat, Peter Kotanko, Inga Bayh, Bernard Canaud, Michael Etter, Emanuele Gatti, Aileen Grassmann, Yuedong Wang, Cristina Marelli, Laura Scatizzi, Andrea Stopper, Frank M van der Sande, Jeroen Kooman

RESULTSIn 37,345 hemodialysis patients, median (25th-75th percentile) LTI and FTI were 12.2 (10.3-14.5) and 9.8 (6.6-12.4) kg/m(2), respectively. Median (25th-75th percentile) follow-up time was 266 (132-379) days; 3458 (9.2%) patients died during follow-up. Mortality was lowest with both LTI and FTI in the 10th-90th percentile (reference group) and significantly higher at the lower LTI and FTI extreme (hazard ratio [HR], 3.37; 95% confidence interval [95% CI], 2.94 to 3.87; P<0.001). Survival was best with LTI between 15 and 20 kg/m(2) and FTI between 4 and 15 kg/m(2) (probability of death during follow-up: <5%). When taking the relation between both compartments into account, the interaction was significant (P=0.01). Higher FTI appeared protective in patients with low LTI (HR, 3.37; 95% CI, 2.94 to 3.87; P<0.001 at low LTI-low FTI, decreasing to HR, 1.79; 95% CI, 1.47 to 2.17; P<0.001 at low LTI-high FTI).CONCLUSIONSThis large international study indicates best survival in patients with both LTI and FTI in the 10th-90th percentiles of a healthy population. In analyses of body composition, both lean tissue and fat tissue compartments and also their relationship should be considered.BACKGROUND AND OBJECTIVESHigh body mass index appears protective in hemodialysis patients, but uncertainty prevails regarding which components of body composition, fat or lean body mass, are primarily associated with survival.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSData between April 2006 and December 2012 were extracted from the Fresenius Medical Care Europe subset of the international MONitoring Dialysis Outcomes initiative. Fresenius Medical Care Europe archives a unique repository of predialysis body composition measurements determined by multifrequency bioimpedance (BCM Body Composition Monitor). The BCM Body Composition Monitor reports lean tissue indices (LTIs) and fat tissue indices (FTIs), which are the respective tissue masses normalized to height squared, relative to an age- and sex-matched healthy population. The relationship between LTI and FTI and all-cause mortality was studied by Kaplan-Meier analysis, multivariate Cox regression, and smoothing spline ANOVA logistic regression.