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TRIAL REGISTRATIONClinicaltrials.gov NCT05828823. Registered on 25 April 2023.DISCUSSIONOur proposal challenges the status quo of HD care delivery. Our overarching hypothesis posits that CMIHD is non-inferior to CHD. If successful, the results will positively impact one of the highest-burdened patient populations and their caregivers.BACKGROUNDMost patients starting chronic in-center hemodialysis (HD) receive conventional hemodialysis (CHD) with three sessions per week targeting specific biochemical clearance. Observational studies suggest that patients with residual kidney function can safely be treated with incremental prescriptions of HD, starting with less frequent sessions and later adjusting to thrice-weekly HD. This trial aims to show objectively that clinically matched incremental HD (CMIHD) is non-inferior to CHD in eligible patients.METHODSAn unblinded, parallel-group, randomized controlled trial will be conducted across diverse healthcare systems and dialysis organizations in the USA. Adult patients initiating chronic hemodialysis (HD) at participating centers will be screened. Eligibility criteria include receipt of fewer than 18 treatments of HD and residual kidney function defined as kidney urea clearance ≥3.5 mL/min/1.73 m2 and urine output ≥500 mL/24 h. The 1:1 randomization, stratified by site and dialysis vascular access type, assigns patients to either CMIHD (intervention group) or CHD (control group). The CMIHD group will be treated with twice-weekly HD and adjuvant pharmacologic therapy (i.e., oral loop diuretics, sodium bicarbonate, and potassium binders). The CHD group will receive thrice-weekly HD according to usual care. Throughout the study, patients undergo timed urine collection and fill out questionnaires. CMIHD will progress to thrice-weekly HD based on clinical manifestations or changes in residual kidney function. Caregivers of enrolled patients are invited to complete semi-annual questionnaires. The primary outcome is a composite of patients' all-cause death, hospitalizations, or emergency department visits at 2 years. Secondary outcomes include patient- and caregiver-reported outcomes. We aim to enroll 350 patients, which provides ≥85% power to detect an incidence rate ratio (IRR) of 0.9 between CMIHD and CHD with an IRR non-inferiority of 1.20 (α = 0.025, one-tailed test, 20% dropout rate, average of 2.06 years of HD per patient participant), and 150 caregiver participants (of enrolled patients).

Individuals afflicted with advanced kidney dysfunction who require dialysis for medical management exhibit different degrees of native kidney function, called residual kidney function (RKF), ranging from nil to appreciable levels. The primary focus of this manuscript is to delve into the concept of RKF, a pivotal yet under-represented topic in nephrology. To begin, we unpack the definition and intrinsic nature of RKF. We then juxtapose the efficiency of RKF against that of hemodialysis in preserving homeostatic equilibrium and facilitating physiological functions. Given the complex interplay of RKF and overall patient health, we shed light on the extent of its influence on patient outcomes, particularly in those living with advanced kidney dysfunction and on dialysis. This manuscript subsequently presents methodologies and measures to assess RKF, concluding with the potential benefits of targeted interventions aimed at preserving RKF.

RESULTSThe intervention group showed an improved median percentage of hemoglobin measurements within target at 47% (interquartile range, 39–58), with a 10% point median difference between the two groups (95% confidence interval, 3 to 16; P = 0.008). The odds ratio of being within the hemoglobin target in the standard-of-care group compared with the group receiving the personalized ESA recommendations was 0.68 (95% confidence interval, 0.51 to 0.92). The variability of hemoglobin levels decreased in the intervention group, with the percentage of patients experiencing fluctuating hemoglobin levels being 45% versus 82% in the standard-of-care group. ESA usage was reduced by approximately 25% in the intervention group.KEY POINTSWe conducted a randomized controlled pilot trial in patients on hemodialysis using a physiology-based individualized anemia therapy assistance software. Patients in the group receiving erythropoiesis-stimulating agent dose recommendations from the novel software showed improvement in hemoglobin stability and erythropoiesis-stimulating agent utilization.CONCLUSIONSOur results demonstrated an improved hemoglobin target attainment and variability by using personalized ESA recommendations using the physiology-based anemia therapy assistance software.CLINICAL TRIAL REGISTRATION NUMBER:NCT04360902.BACKGROUNDAnemia is common among patients on hemodialysis. Maintaining stable hemoglobin levels within predefined target levels can be challenging, particularly in patients with frequent hemoglobin fluctuations both above and below the desired targets. We conducted a multicenter, randomized controlled trial comparing our anemia therapy assistance software against a standard population-based anemia treatment protocol. We hypothesized that personalized dosing of erythropoiesis-stimulating agents (ESAs) improves hemoglobin target attainment.METHODSNinety-six patients undergoing hemodialysis and receiving methoxy polyethylene glycol-epoetin beta were randomized 1:1 to the intervention group (personalized ESA dose recommendations computed by the software) or the standard-of-care group for 26 weeks. The therapy assistance software combined a physiology-based mathematical model and a model predictive controller designed to stabilize hemoglobin levels within a tight target range (10–11 g/dl). The primary outcome measure was the percentage of hemoglobin measurements within the target. Secondary outcome measures included measures of hemoglobin variability and ESA utilization.

The relationship between sodium, blood pressure and extracellular volume could not be more pronounced or complex than in a dialysis patient. We review the patients' sources of sodium exposure in the form of dietary salt intake, medication administration, and the dialysis treatment itself. In addition, the roles dialysis modalities, hemodialysis types, and dialysis fluid sodium concentration have on blood pressure, intradialytic symptoms, and interdialytic weight gain affect patient outcomes are discussed. We review whether sodium restriction (reduced salt intake), alteration in dialysis fluid sodium concentration and the different dialysis types have any impact on blood pressure, intradialytic symptoms, and interdialytic weight gain.

RESULTSThe mean duration of dialysis session was 418 ± 54 minutes in HHD and 242 ± 10 minutes in patients on ICHD. All-cause mortality rate was 3.76 and 6.27 per 100 patient-years in the HHD and the ICHD groups, respectively. In the intention-to-treat analysis, HHD was associated with a 40% lower risk for all-cause mortality than ICHD (hazard ratio [HR] = 0.60; 95% confidence interval [CI] 0.45 to 0.80; P < 0.001). In HHD, the 5-year technical survival was 86.5%. HHD treatment provided better phosphate and blood pressure (BP) control, improvements in nutrition and inflammation, and reduction in hospitalization days and medication requirement.CONCLUSIONThese results indicate that extended HHD is associated with higher survival and better outcomes compared to ICHD.INTRODUCTIONMore frequent and/or longer hemodialysis (HD) has been associated with improvements in numerous clinical outcomes in patients on dialysis. Home HD (HHD), which allows more frequent and/or longer dialysis with lower cost and flexibility in treatment planning, is not widely used worldwide. Although, retrospective studies have indicated better survival with HHD, this issue remains controversial. In this multicenter study, we compared thrice-weekly extended HHD with in-center conventional HD (ICHD) in a large patient population with a long-term follow-up.METHODSWe matched 349 patients starting HHD between 2010 and 2014 with 1047 concurrent patients on ICHD by using propensity scores. Patients were followed-up with from their respective baseline until September 30, 2018. The primary outcome was overall survival. Secondary outcomes were technique survival; hospitalization; and changes in clinical, laboratory, and medication parameters.

RESULTSTwelve anuric patients were studied (six female patients; 44±19 years; dialysis vintage 35.2±28 months). The blood flow was 369±23 ml/min, dialysate flow was 495±61 ml/min, and ultrafiltration volume was 2.8±0.74 L. No significant differences were found regarding the removal of B2M, vitamin B12, and water-soluble solutes between dialytic modalities and dialyzers. Albumin and total protein loss were significantly higher in MCO groups than HFX groups when compared with the same modality. HDF groups had significantly higher albumin and total protein loss than HD groups when compared with the same dialyzer. MCO-HDF showed the highest protein loss among all groups.KEY POINTSHDF and MCO have shown greater clearance of middle-size uremic solutes in comparison with HF dialyzers; MCO has never been studied in HDF. MCO in HDF does not increase the clearance of B2M and results in a higher loss of albumin.CONCLUSIONSMCO-HD is not superior to HFX-HD and HFX-HDF for both middle molecule and water-soluble solute removal. Protein loss was more pronounced with MCO when compared with HFX on both HD and HDF modalities. MCO-HDF has no additional benefits regarding better removal of B2M but resulted in greater protein loss than MCO-HD.BACKGROUNDMiddle molecule removal and albumin loss have been studied in medium cutoff (MCO) membranes on hemodialysis (HD). It is unknown whether hemodiafiltration (HDF) with MCO membranes provides additional benefit. We aimed to compare the removal of small solutes and β2-microglobulin (B2M), albumin, and total proteins between MCO and high-flux (HFX) membranes with both HD and HDF, respectively.METHODSThe cross-over study comprised 4 weeks, one each with postdilutional HDF using HFX (HFX-HDF), MCO (MCO-HDF), HD with HFX (HFX-HD), and MCO (MCO-HD). MCO and HFX differ with respect to several characteristics, including membrane composition, pore size distribution, and surface area (HFX, 2.5 m2; MCO, 1.7 m2). There were two study treatments per week, one after the long interdialytic interval and another midweek. Reduction ratios of vitamin B12, B2M, phosphate, uric acid, and urea corrected for hemoconcentration were computed. Dialysis albumin and total protein loss during the treatment were quantified from dialysate samples.

RESULTSIn the studied 396,358 patients, the average ultrafiltration rate in ml/h was related to postdialysis weight (W) in kg: 3W+330. Ultrafiltration rates associated with 20% or 40% higher weight-specific mortality risk were 3W+500 and 3W+630 ml/h, respectively, and were 70 ml/h higher in men than in women. Nineteen percent or 7.5% of patients exceeded ultrafiltration rates associated with a 20% or 40% higher mortality risk, respectively. Low ultrafiltration rates were associated with subsequent weight loss. Ultrafiltration rates associated with a given mortality risk were lower in high-body weight older patients and higher in patients on dialysis for more than 3 years.CONCLUSIONSUltrafiltration rates associated with various levels of higher mortality risk depend on body weight, but not in a 1:1 ratio, and are different in men versus women, in high-body weight older patients, and in high-vintage patients.BACKGROUNDWe hypothesized that the association of ultrafiltration rate with mortality in hemodialysis patients was differentially affected by weight and sex and sought to derive a sex- and weight-indexed ultrafiltration rate measure that captures the differential effects of these parameters on the association of ultrafiltration rate with mortality.METHODSData were analyzed from the US Fresenius Kidney Care (FKC) database for 1 year after patient entry into a FKC dialysis unit (baseline) and over 2 years of follow-up for patients receiving thrice-weekly in-center hemodialysis. To investigate the joint effect of baseline-year ultrafiltration rate and postdialysis weight on survival, we fit Cox proportional hazards models using bivariate tensor product spline functions and constructed contour plots of weight-specific mortality hazard ratios over the entire range of ultrafiltration rate values and postdialysis weights (W).

RESULTSWe observed positive associations between inclement weather and missed appointment (rainfall, hurricane and tropical storm, snowfall, snow depth, and wind advisory) when compared with noninclement weather days. The risk of missed appointments was most pronounced during the day of inclement weather (lag 0) for rainfall (incidence rate ratio [RR], 1.03 per 10-mm rainfall; 95% confidence interval [CI], 1.02 to 1.03) and snowfall (RR, 1.02; 95% CI, 1.01 to 1.02). Over 7 days (lag 0-6), hurricane and tropical storm exposures were associated with a 55% higher risk of missed appointments (RR, 1.55; 95% CI, 1.22 to 1.98). Similarly, 7-day cumulative exposure to sustained wind advisories was associated with 29% higher risk (RR, 1.29; 95% CI, 1.25 to 1.31), while wind gusts advisories showed a 34% higher risk (RR, 1.34; 95% CI, 1.29 to 1.39) of missed appointment.CONCLUSIONSInclement weather was associated with higher risk of missed hemodialysis appointments within the Northeastern United States. Furthermore, the association between inclement weather and missed hemodialysis appointments persisted for several days, depending on the inclement weather type.BACKGROUNDNonadherence to hemodialysis appointments could potentially result in health complications that can influence morbidity and mortality. We examined the association between different types of inclement weather and hemodialysis appointment adherence.METHODSWe analyzed health records of 60,135 patients with kidney failure who received in-center hemodialysis treatment at Fresenius Kidney Care clinics across the Northeastern US counties during 2001-2019. County-level daily meteorological data on rainfall, hurricane and tropical storm events, snowfall, snow depth, and wind speed were extracted using National Oceanic and Atmosphere Agency data sources. A time-stratified case-crossover study design with conditional Poisson regression was used to estimate the effect of inclement weather exposures within the Northeastern US region. We applied a distributed lag nonlinear model framework to evaluate the delayed effect of inclement weather for up to 1 week.

No abstract available

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.

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.

Our bones are constantly being renewed in a fine-tuned cycle of destruction and formation that helps keep them healthy and strong. However, this process can become imbalanced and lead to osteoporosis, where the bones are weakened and have a high risk of fracturing. This is particularly common post-menopause, with one in three women over the age of 50 experiencing a broken bone due to osteoporosis. There are several drug types available for treating osteoporosis, which work in different ways to strengthen bones. These drugs can be taken individually or combined, meaning that a huge number of drug combinations and treatment strategies are theoretically possible. However, it is not practical to test the effectiveness of all of these options in human trials. This could mean that patients are not getting the maximum potential benefit from the drugs available. Jörg et al. developed a mathematical model to predict how different osteoporosis drugs affect the process of bone renewal in the human body. The model could then simulate the effect of changing the order in which the therapies were taken, which showed that the sequence had a considerable impact on the efficacy of the treatment. This occurs because different drugs can interact with each other, leading to an improved outcome when they work in the right order. These results suggest that people with osteoporosis may benefit from altered treatment schemes without changing the type or amount of medication taken. The model could suggest new treatment combinations that reduce the risk of bone fracture, potentially even developing personalised plans for individual patients based on routine clinical measurements in response to different drugs.

DISCUSSIONAlthough segmental eight-point bioimpedance techniques provided comparable TBW measurements not affected by standing over a period of 10-15 min, the ECW/TBW ratio appeared to be significantly lower in InBody compared with Seca and Hydra. Results from our study showed lack of agreement between different bioimpedance devices; direct comparison of ECW, ICW, and ECW/TBW between different devices should be avoided and clinicians should use the same device to track the fluid status in their HD population in a longitudinal direction.INTRODUCTIONSegmental eight-point bioimpedance has been increasingly used in practice. However, whether changes in bioimpedance analysis components before and after hemodialysis (HD) using this technique in a standing position is comparable to traditional whole-body wrist-to-ankle method is still unclear. We aimed to investigate the differences between two eight-point devices (InBody 770 and Seca mBCA 514) and one wrist-to-ankle (Hydra 4200) in HD patients and healthy subjects in a standing position.FINDINGSOverall, total body water (TBW) was not different between the three devices, but InBody showed lower extracellular water (ECW) and higher intracellular water (ICW) compared to the other two devices. When intradialytic weight loss was used as a surrogate for changes in ECW (∆ECW) and changes in TBW (∆TBW), ∆ECW was underestimated by Hydra (-0.79 ± 0.89 L, p < 0.01), InBody (-1.44 ± 0.65 L, p < 0.0001), and Seca (-0.32 ± 1.34, n.s.). ∆TBW was underestimated by Hydra (-1.14 ± 2.81 L, n.s.) and InBody (-0.52 ± 0.85 L, p < 0.05) but overestimated by Seca (+0.93 ± 3.55 L, n.s.).METHODSThirteen HD patients were studied pre- and post-HD, and 12 healthy subjects once. Four measurements were performed in the following order: InBody; Seca; Hydra; and InBody again. Electrical equivalent models by each bioimpedance method and the fluid volume estimates by each device were also compared.

Diagnosis of fluid overload (FO) in early stage is essential to manage fluid balance of patients with chronic kidney disease (CKD) and to prevent cardiovascular disease (CVD). However, the identification of fluid status in patients with CKD is largely dependent on the physician's clinical acumen. The ratio of fluid overload to extracellular volume (FO/ECV) has been used as a reference to assess fluid status. The primary aim of this study was to compare FO/ECV with other bioimpedance methods and clinical assessments in patients with CKD. Whole body ECV, intracellular volume (ICV), total body water (TBW), and calf normalized resistivity (CNR) were measured (Hydra 4200). Thresholds of FO utilizing CNR and ECV/TBW were derived by receiver operator characteristic (ROC) analysis based on data from pooled patients with CKD and healthy subjects (HSs). Clinical assessments of FO in patients with CKD were performed by nephrologists. Patients with CKD (stage 3 and stage 4) (n = 50) and HSs (n = 189) were studied. The thresholds of FO were ≤14.3 (10-2 Ωm3/kg) for females and ≤13.1 (10-2 Ωm3/kg) for males using CNR and ≥0.445 in females and ≥0.434 in males using ECV/TBW. FO was diagnosed in 78%, 62%, and 52% of patients with CKD by CNR, FO/ECV, and ECV/TBW, respectively, whereas only 24% of patients with CKD were diagnosed to be FO by clinical assessment. The proportion of FO in patients with nondialysis CKD was largely underestimated by clinical assessment compared with FO/ECV, CNR, and ECV/TBW. CNR and FO/ECV methods were more sensitive than ECV/TBW in identifying fluid overload in these patients with CKD.NEW & NOTEWORTHY We found that fluid overload (FO) in patients with nondialysis CKD was largely underestimated by clinical assessment compared with bioimpedance methods, which was majorly due to lack of appropriate techniques to assess FO. In addition, although degree of FO by bioimpedance markers positively correlated with the age in healthy subjects (HSs), no difference was observed in the three hydration markers between groups of 50 ≤ age <70 yr and age ≥70 yr in the patients with CKD.

RESULTSIn the studied 2542 patients, UFR not scaled to body weight was strongly associated with MHR, whereas postdialysis weight was inversely associated with MHR. MHR crossed 1.5 when unscaled UFR exceeded 1000 ml/h, and this relationship was largely independent of postdialysis weight in the range of 80 to 140 kg. A UFR warning level associated with a lower MHR of 1.3 would be 900 ml/h, whereas the UFR associated with an MHR of 1.0 was patient-size dependent. The MHR when exceeding a UFR threshold of 13 ml/h per kg was dependent on patient weight (MHR = 1.20, 1.45, and >2.0 for a 60, 80, and 100 kg patient, respectively).CONCLUSIONUFR thresholds based on unscaled UFR give more uniform risk levels for patients of different sizes than thresholds based on UFR/kg.INTRODUCTIONOne proposed threshold ultrafiltration rate (UFR) of concern in hemodialysis patients is 13 ml/h per kg. We evaluated associations among UFR, postdialysis weight, and mortality to determine whether exceeding such a threshold would result in similar levels of risk for patients of different body weights.METHODSData were analyzed in this retrospective cohort study for 1 year following dialysis initiation (baseline) and over 2 years of follow-up in incident patients receiving thrice-weekly in-center hemodialysis. Patient-level UFR was averaged over the baseline period. To investigate the joint effect of UFR and postdialysis weight on survival, we fit Cox proportional hazards models using bivariate tensor product spline functions, adjusting for sex, race, age, diabetes, and predialysis serum albumin, phosphorus, and systolic blood pressure (BP). We constructed contour plots of mortality hazard ratios (MHRs) over the entire range of UFR values and postdialysis weights.

Herbal medicine, a form of complementary and alternative medicine (CAM), is used throughout the world, in both developing and developed countries. The ingredients in herbal medicines are not standardized by any regulatory agency. Variability exists in the ingredients as well as in their concentrations. Plant products may become contaminated with bacteria and fungi during storage. Therefore, harm can occur to the kidney, liver, and blood components after ingestion. We encourage scientific studies to identify the active ingredients in herbs and to standardize their concentrations in all herbal preparations. Rigorous studies need to be performed in order to understand the effect of herbal ingredients on different organ systems as well as these substances' interaction with other medications.

No abstract available

RESULTSFrom 2001 to 2016, the sample population consisted of 43,338 ESKD patients. We recorded 5217 deaths and 78,433 hospital admissions. A 10-unit increase in PM2.5 concentration was associated with a 5% increase in ACM (rate ratio [RRLag0-3]: 1.05, 95% CI: 1.00-1.10) and same-day O3 (RRLag0: 1.02, 95% CI: 1.01-1.03) after adjusting for extreme heat exposures. Mortality models suggest evidence of interaction and effect measure modification, though not always simultaneously. ACM risk increased up to 8% when daily ozone concentrations exceeded National Ambient Air Quality Standards established by the United States, but the increases in risk were considerably higher during EHE days across lag periods.CONCLUSIONOur findings suggest interdependent effects of EHE and air pollution among ESKD patients for all-cause mortality risks. National level assessments are needed to consider the ESKD population as a sensitive population and inform treatment protocols during extreme heat and degraded pollution episodes.BACKGROUNDIncreasing number of studies have linked air pollution exposure with renal function decline and disease. However, there is a lack of data on its impact among end-stage kidney disease (ESKD) patients and its potential modifying effect from extreme heat events (EHE).METHODSFresenius Kidney Care records from 28 selected northeastern US counties were used to pool daily all-cause mortality (ACM) and all-cause hospital admissions (ACHA) counts. County-level daily ambient PM2.5 and ozone (O3) were estimated using a high-resolution spatiotemporal coupled climate-air quality model and matched to ESKD patients based on ZIP codes of treatment sites. We used time-stratified case-crossover analyses to characterize acute exposures using individual and cumulative lag exposures for up to 3 days (Lag 0-3) by using a distributed lag nonlinear model framework. We used a nested model comparison hypothesis test to evaluate for interaction effects between air pollutants and EHE and stratification analyses to estimate effect measures modified by EHE days.

DISCUSSIONWhile about half of the patients had normal fluid status pre-HD, a considerable proportion of patients was either fluid overloaded or depleted, indicating the need for tools to objectively quantify fluid status.INTRODUCTIONInadequate fluid status remains a key driver of cardiovascular morbidity and mortality in chronic hemodialysis (HD) patients. Quantification of fluid overload (FO) using bioimpedance spectroscopy (BIS) has become standard in many countries. To date, no BIS device has been approved in the United States for fluid status assessment in kidney patients. Therefore, no previous quantification of fluid status in US kidney patients using BIS has been reported. Our aim was to conduct a cross-sectional BIS-based assessment of fluid status in an urban US HD population.FINDINGSWe studied 170 urban HD patients (age 61 ± 14 years, 60% male). Pre- and post-HD FO (mean ± SD), were 2.2 ± 2.4 and -0.2 ± 2.7 L, respectively. Pre-HD, 43% of patients were fluid overloaded, 53% normally hydrated, and 4% fluid depleted. Post-HD, 12% were fluid overloaded, 55% normohydrated and 32% fluid depleted. Only 48% of fluid overloaded patients were hypertensive, while 38% were normotensive and 14% hypotensive. Fluid status did not differ significantly between African Americans (N = 90) and Caucasians (N = 61).METHODSWe determined fluid status in chronic HD patients using whole body BIS (Body Composition Monitor, BCM). The BCM reports FO in liters; negative FO denotes fluid depletion. Measurements were performed before dialysis. Post-HD FO was estimated by subtracting the intradialytic weight loss from the pre-HD FO.

RESULTSIn 1,632 patients from RRI, the CVC prevalence at month 1 was 64% and 97% among 174 HC patients. The conversion rate was 31.7% in RRI and 10.6% in HC. CVC to non-central venous catheter (NON-CVC) conversion reduced the risk of hospitalization in both HC (aHR 0.38 [95% CI: 0.21-0.68], p = 0.001) and RRI (aHR 0.84 [95% CI: 0.73-0.93], p = 0.001). NON-CVC patients had a lower mortality risk in both populations.INTRODUCTIONCentral venous catheter (CVC) as vascular access in hemodialysis (HD) associates with adverse outcomes. Early CVC to fistula or graft conversion improves these outcomes. While socioeconomic disparities between the USA and Mexico exist, little is known about CVC prevalence and conversion rates in uninsured Mexican HD patients. We examined vascular access practice patterns and their effects on survival and hospitalization rates among uninsured Mexican HD patients, in comparison with HD patients who initiated treatment in the USA.DISCUSSION/CONCLUSIONCVC prevalence and conversion rates of CVC to NON-CVC differed between the US and Mexican patients. An association exists between vascular access type and hospitalization and mortality risk. Prospective studies are needed to evaluate if accelerated and systematic catheter use reduction would improve outcomes in these populations.METHODSIn this retrospective study of incident HD patients at Hospital Civil (HC; Guadalajara, MX) and the Renal Research Institute (RRI; USA), we categorized patients by the vascular access at the first month of HD and after the following 6 months. Factors associated with continued CVC use were identified by a logistic regression model. We developed multivariate Cox proportional hazards models to investigate the effects of access and conversion on mortality and hospitalization over an 18-month follow-up period.

RESULTSWe randomized 195 patients (HDF 97; HD 98) between August 2016 and October 2017. Despite the achievement of a high convective volume in the majority of sessions and a positive impact on solute removal, the treatment effect HDF on the primary outcome was +538 [95% confidence interval (CI) -330 to 1407] steps/24 h after dialysis compared with HD, and was not statistically significant. Despite a lack of statistical significance, the observed size of the treatment effect was modest and driven by steps taken between 1.5 and 24.0 h after dialysis, in particular between 20 and 24 h (+197 steps; 95% CI -95 to 488).CONCLUSIONSHDF did not have a statistically significant treatment effect on PA 24 h following dialysis, albeit effect sizes may be clinically meaningful and deserve further investigation.BACKGROUNDDialysis patients are typically inactive and their physical activity (PA) decreases over time. Uremic toxicity has been suggested as a potential causal factor of low PA in dialysis patients. Post-dilution high-volume online hemodiafiltration (HDF) provides greater higher molecular weight removal and studies suggest better clinical/patient-reported outcomes compared with hemodialysis (HD).METHODSHDFIT was a randomized controlled trial at 13 clinics in Brazil that aimed to investigate the effects of HDF on measured PA (step counts) as a primary outcome. Stable HD patients (vintage 3-24 months) were randomized to receive HDF or high-flux HD. Treatment effect of HDF on the primary outcome from baseline to 3 and 6 months was estimated using a linear mixed-effects model.

RESULTSIn 197 enrolled subjects in the FHN Daily Trial, the treatment effect of frequent HD on ∆LVM was modified by SNa. When the FHN Daily Trial participants are divided into lower and higher predialysis SNa groups (less and greater than 138 mEq/L), the LVM reduction in the lower group was substantially higher (-28.0 [95% CI -40.5 to -15.4] g) than in the higher predialysis SNa group (-2.0 [95% CI -15.5 to 11.5] g). Accounting for GNa, TIFL also showed more pronounced effects among patients with higher GNa or higher TIFL. Results in the Nocturnal Trial were similar in direction and magnitude but did not reach statistical significance.INTRODUCTIONThe Frequent Hemodialysis Network (FHN) Daily and Nocturnal trials aimed to compare the effects of hemodialysis (HD) given 6 versus 3 times per week. More frequent in-center HD significantly reduced left-ventricular mass (LVM), with more pronounced effects in patients with low urine volumes. In this study, we aimed to explore another potential effect modifier: the predialysis serum sodium (SNa) and related proxies of plasma tonicity.DISCUSSION/CONCLUSIONIn the FHN Daily Trial, the favorable effects of frequent HD on left-ventricular hypertrophy were more pronounced among patients with lower predialysis SNa and higher GNa and TIFL. Whether these metrics can be used to identify patients most likely to benefit from frequent HD or other dialytic or nondialytic interventions remains to be determined. Prospective, adequately powered studies studying the effect of GNa reduction on mortality and hospitalization are needed.METHODSUsing data from the FHN Daily and Nocturnal Trials, we compared the effects of frequent HD on LVM among patients stratified by SNa, dialysate-to-predialysis serum-sodium gradient (GNa), systolic and diastolic blood pressure, time-integrated sodium-adjusted fluid load (TIFL), and extracellular fluid volume estimated by bioelectrical impedance analysis.

RESULTSBased on Lag 2- Lag 1 temporal ordering, 1 °C increase in daily TMAX was associated with increased hazard of ACHA by 1.4% (adjusted hazard ratio (HR), 1.014; 95% confidence interval, 1.007-1.021) and ACM 7.5% (adjusted HR, 1.075, 1.050-1.100). Short-term lag exposures to 1 °C increase in temperature predicted mean reductions in IDWG and preSBP by 0.013-0.015% and 0.168-0.229 mmHg, respectively. Mediation analysis for ACHA identified significant indirect effects for all three studied pathways (preSBP, IDWG, and preSBP + IDWG) and significant indirect effects for IDWG and conjoined preSBP + IDWG pathways for ACM. Of note, only 1.03% of the association between temperature and ACM was mediated through preSBP. The mechanistic path for IDWG, independent of preSBP, demonstrated inconsistent mediation and, consequently, potential suppression effects in ACHA (-15.5%) and ACM (-6.3%) based on combined pathway models. Proportion mediated estimates from preSBP + IDWG pathways achieved 2.2% and 0.3% in combined pathway analysis for ACHA and ACM outcomes, respectively. Lag 2 discrete-time ACM mediation models exhibited consistent mediation for all three pathways suggesting that 2-day lag in IDWG and preSBP responses can explain 2.11% and 4.41% of total effect association between temperature and mortality, respectively.CONCLUSIONWe corroborated the previously reported association between ambient temperature, ACHA and ACM. Our results foster the understanding of potential physiological linkages that may explain or suppress temperature-driven hospital admissions and mortality risks. Of note, concomitant changes in preSBP and IDWG may have little intermediary effect when analyzed in combined pathway models. These findings advance our assessment of candidate interventions to reduce the impact of outdoor temperature change on ESKD patients.BACKGROUNDTypical thermoregulatory responses to elevated temperatures among healthy individuals include reduced blood pressure and perspiration. Individuals with end-stage kidney disease (ESKD) are susceptible to systemic fluctuations caused by ambient temperature changes that may increase morbidity and mortality. We investigated whether pre-dialysis systolic blood pressure (preSBP) and interdialytic weight gain (IDWG) can independently mediate the association between ambient temperature, all-cause hospital admissions (ACHA), and all-cause mortality (ACM).METHODSThe study population consisted of ESKD patients receiving hemodialysis treatments at Fresenius Medical Care facilities in Philadelphia County, PA, from 2011 to 2019 (n = 1981). Within a time-to-event framework, we estimated the association between daily maximum dry-bulb temperature (TMAX) and, as separate models, ACHA and ACM during warmer calendar months. Clinically measured preSBP and IDWG responses to temperature increases were estimated using linear mixed effect models. We employed the difference (c-c') method to decompose total effect models for ACHA and ACM using preSBP and IDWG as time-dependent mediators. Covariate adjustments for exposure-mediator and total and direct effect models include age, race, ethnicity, blood pressure medication use, treatment location, preSBP, and IDWG. We considered lags up to two days for exposure and 1-day lag for mediator variables (Lag 2-Lag 1) to assure temporality between exposure-outcome models. Sensitivity analyses for 2-day (Lag 2-only) and 1-day (Lag 1-only) lag structures were also conducted.

RESULTSFrom 2017 to 2020, we analyzed 288 AKI patients. The mean age was 55.3 years, 60.7% were male, AKI KDIGO stage 3 was present in 50.5% of them, sepsis was the main etiology 50.3%, and 72 (25%) patients started KRT. The overall survival was 84.4%. Fluid adjustment was the only intervention associated with a decreased risk for starting KRT (odds ratio [OR]: 0.58, 95% confidence interval [CI]: 0.48-0.70, and p ≤ 0.001) and AKI progression to stage 3 (OR: 0.59, 95% CI: 0.49-0.71, and p ≤ 0.001). Receiving vasopressors and KRT were associated with mortality. None of the interventions studied was associated with reducing the risk of death.CONCLUSIONSIn this prospective cohort study of AKI patients, we found for the first time that early nephrologist intervention and fluid prescription adjustment were associated with lower risk of starting KRT and progression to AKI stage 3.BACKGROUNDBased on the pathophysiology of acute kidney injury (AKI), it is plausible that certain early interventions by the nephrologist could influence its trajectory. In this study, we investigated the impact of 5 early nephrology interventions on starting kidney replacement therapy (KRT), AKI progression, and death.METHODSIn a prospective cohort at the Hospital Civil of Guadalajara, we followed up for 10 days AKI patients in whom a nephrology consultation was requested. We analyzed 5 early interventions of the nephrology team (fluid adjustment, nephrotoxic withdrawal, antibiotic dose adjustment, nutritional adjustment, and removal of hyperchloremic solutions) after the propensity score and multivariate analysis for the risk of starting KRT (primary objective), AKI progression to stage 3, and death (secondary objectives).

RESULTSBetween January 2019 and January 2020 a total of 75 patients with tunnelled catheter insertion were analysed. Catheter replacement at 6-month occur in 10 (13.3%) patients. By multivariate analysis, the incorrect catheter tip position (SVC) (OR 1.23, 95% CI 1.07-1.42, p <.004), the presence of extrasystoles during the procedure (OR 0.88, 95% CI 0.78-0.98, p = .03), incorrect catheter tug (OR 1.31, 95% CI 1.10-1.55, p = .003), incorrect catheter top position (kinking; OR 1.40, 95% CI 1.04-1.88, p = .02) and catheter-related bloodstream infection (OR 2.60, 95% CI 2.09-3.25, p <.001) were the only variables associated with catheter replacement at 6-month follow-up.AIMTunnelled haemodialysis (HD) catheters can be used instantly, but there are several anatomical variables that could impact it survival. This study aimed to examine the impact of different novel anatomic variables, with catheter replacement.CONCLUSIONThe risk of catheter replacement at 6-month follow-up could be attenuated by avoiding incorrect catheter tug and top position, and by placing the vascular catheter tip in the CAJ and MDA.METHODSIn a single-centre a prospective cohort in chronic kidney disease G5 patients were conducted. The primary outcome was to determine the factors associated with catheter replacement during the first 6-month of follow-up. All procedures were performed without fluoroscopy. Three anatomic regions for catheter tip position were established: considered as superior vena cava (SVC), cavo-atrial junction (CAJ) and mid-to deep atrium (MDA). Many other anatomical variables were measured. Catheter-related bloodstream infection was also included.

RESULTSSeventeen chronic HD patients (11 males, age 54.1 ± 18.7 years) completed the study. The average priming and rinsing volumes were 236.7 ± 77.5 and 245.0 ± 91.8 mL respectively. The mean IDWG did not significantly change (2.52 ± 0.88 kg in Phase 1; 2.28 ± 0.70 kg in Phase 2; and 2.51 ± 1.2 kg in Phase 3). No differences in blood pressures, intradialytic symptoms or thirst were observed.MATERIALS AND METHODSWe enrolled non-diabetic and anuric stable HD patients. First, the extracorporeal circuit was primed and rinsed with approximately 200-250 mL of isotonic saline during 4 weeks (Phase 1), subsequently a similar volume of a 5% dextrose solution replaced the saline for another 4 weeks (Phase 2), followed by another 4 weeks of saline (Phase 3). We collected data on interdialytic weight gain (IDWG), pre- and post-dialysis blood pressure, intradialytic symptoms, and thirst.CONCLUSIONSReplacing saline by 5% dextrose for priming and rinsing is feasible in stable HD patients and may reduce intradialytic sodium loading. A non-significant trend toward a lower IDWG was observed when 5% dextrose was used. Prospective studies with a larger sample size and longer follow-up are needed to gain further insight into the possible effects of using alternate priming and rinsing solutions lowering intradialytic sodium loading.TRIAL REGISTRATIONIdentifier NCT01168947 (ClinicalTrials.gov).INTRODUCTIONExcess sodium intake and consequent volume overload are major clinical problems in hemodialysis (HD) contributing to adverse outcomes. Saline used for priming and rinsing of the extracorporeal circuit is a potentially underappreciated source of intradialytic sodium gain. We aimed to examine the feasibility and clinical effects of replacing saline as the priming and rinsing fluid by a 5% dextrose solution.

Intradialytic hypotension (IDH) is a common complication of hemodialysis, but there is no data about the time of onset during treatment. Here we describe the incidence of IDH throughout hemodialysis and associations of time of hypotension with clinical parameters and survival by analyzing data from 21 dialysis clinics in the United States to include 785682 treatments from 4348 patients. IDH was defined as a systolic blood pressure of 90 mmHg or under while IDH incidence was calculated in 30-minute intervals throughout the hemodialysis session. Associations of time of IDH with clinical and treatment parameters were explored using logistic regression and with survival using Cox-regression. Sensitivity analysis considered further IDH definitions. IDH occurred in 12% of sessions at a median time interval of 120-149 minutes. There was no notable change in IDH incidence across hemodialysis intervals (range: 2.6-3.2 episodes per 100 session-intervals). Relative blood volume and ultrafiltration volume did not notably associate with IDH in the first 90 minutes but did thereafter. Associations between central venous but not arterial oxygen saturation and IDH were present throughout hemodialysis. Patients prone to IDH early as compared to late in a session had worse survival. Sensitivity analyses suggested IDH definition affects time of onset but other analyses were comparable. Thus, our study highlights the incidence of IDH during the early part of hemodialysis which, when compared to later episodes, associates with clinical parameters and mortality.

RESULTSAmong 98,616 incident HD patients (age 62.6 ± 14.4 years, 57.8% male) who responded to DRT survey, a higher spKt/V in the incident period was associated with 13.5% (OR = 0.865; 95%CI 0.801-to-0.935) lower risk of a change to a longer DRT in the first-prevalent year. A higher number of HD treatments with IDH episodes per month in the incident period was associated with a 0.8% (OR = 1.008; 95%CI 1.001-to-1.015) and 1.6% (OR = 1.016; 95%CI 1.006-to-1.027) higher probability of a change to a longer DRT in the first- and second-prevalent years, respectively. Consistently, an increased in incidence of IDH episodes/months was associated to a change to a longer DRT over time.CONCLUSIONSIncident patients who had higher spKt/V and less sessions with IDH episodes had a lower likelihood of changing to a longer DRT in first year of HD. Dose optimization strategies with cardiac stability in fluid removal should be tested.BACKGROUNDDialysis recovery time (DRT) surveys capture the perceived time after HD to return to performing regular activities. Prior studies suggest the majority of HD patients report a DRT > 2 h. However, the profiles of and modifiable dialysis practices associated with changes in DRT relative to the start of dialysis are unknown. We hypothesized hemodialysis (HD) dose and rates of intradialytic hypotension (IDH) would associate with changes in DRT in the first years after initiating dialysis.METHODSWe analyzed data from adult HD patients who responded to a DRT survey ≤180 days from first date of dialysis (FDD) during 2014 to 2017. DRT survey was administered with annual KDQOL survey. DRT survey asks: "How long does it take you to be able to return to your normal activities after your dialysis treatment?" Answers are: < 0.5, 0.5-to-1, 1-to-2, 2-to-4, or > 4 h. An adjusted logistic regression model computed odds ratio for a change to a longer DRT (increase above DRT > 2 h) in reference to a change to a shorter DRT (decrease below DRT < 2 h, or from DRT > 4 h). Changes in DRT were calculated from incident (≤180 days FDD) to first prevalent (> 365-to- ≤ 545 days FDD) and second prevalent (> 730-to- ≤ 910 days FDD) years.

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