Dynamics of Plasma Refill Rate and Intradialytic Hypotension during Hemodialysis: Retrospective Cohort Study with Causal Methodology

Hanjie Zhang, Sabrina Casper, Peter Kotanko, Jochen G Raimann, Christina H Wang, Dan Negoianu, Jesse Y Hsu, Laura M Dember


Background: Attaining the optimal balance between achieving adequate volume removal while preserving organ perfusion is a challenge for patients receiving maintenance hemodialysis. Current strategies to guide ultrafiltration are inadequate.

Methods: We developed an approach to calculate plasma refill rate throughout hemodialysis using hematocrit and ultrafiltration data in a retrospective cohort of patients receiving maintenance hemodialysis at 17 dialysis units from January 2017-October 2019. We studied whether (1) plasma refill rate is associated with traditional risk factors for hemodynamic instability using logistic regression, (2) low starting plasma refill rate is associated with intradialytic hypotension using Cox proportional hazard regression, and (3) time-varying plasma refill rate throughout hemodialysis is associated with hypotension using marginal structural modeling.

Results: During 180,319 hemodialysis sessions among 2554 patients, plasma refill rate had high within- and between-patient variability. Female sex and hypoalbuminemia were associated with low plasma refill rate at multiple time points during the first hour of hemodialysis. Low starting plasma refill rate had higher hazards of intradialytic hypotension while high starting plasma refill rate was protective (HR 1.26, 95% CI 1.18, 1.35 versus HR 0.79, 95% CI 0.73, 0.85, respectively). However, when accounting for time-varying plasma refill rate and time-varying confounders, compared to a moderate plasma refill rate, while a consistently low plasma refill rate was associated with increased risk of hypotension (OR 1.09, 95% CI 1.02, 1.16), a consistently high plasma refill rate had a stronger association with hypotension within the next 15 minutes (OR 1.38, 95% CI 1.30, 1.45).

Conclusions: We present a straightforward technique to quantify plasma refill that could easily integrate with devices that monitor hematocrit during hemodialysis. Our study highlights how examining patterns of plasma refill may enhance our understanding of circulatory changes during hemodialysis, an important step to understanding how current technology might be utilized to improve hemodynamic instability.

Copyright © 2023 by the American Society of Nephrology.

About the Author

Hanjie Zhang, MSc, PhD

Supervisor of Biostatistics and Applied Artificial Intelligence /Machine Learning

Hanjie joined RRI in 2014. She received a master’s degree in statistics from Columbia University, New York, and a PhD in medical science from the University of Maastricht, The Netherlands. Hanjie has been involved in the design of several large cluster-randomized clinical trials and complex statistical analyses in collaboration with the Medical Office, FMCNA...

Jochen G. Raimann, MD, PhD, MPH

Director, Data Analytics

Jochen has worked as a full-time scientist at RRI since his start as a postdoctoral research fellow in 2007. As Senior Manager of Clinical Data Analytics, Jochen conducts epidemiological research in dialysis and oversees many analytical projects. He has first- and co-authored numerous papers and also serves as Associate Editor of the journals Trials and Scientific Reports. ochen earned his MD from the Medical University Graz, his PhD from Maastricht University, and his MPH with a focus on epidemiology and biostatistics from the City University of New York School of Public Health.

Dr. Peter Kotanko, MD

RRI Research Director

SVP, Corporate Research & Development

Peter Kotanko, MD, is Research Director at the Renal Research Institute (RRI), New York. Prior to joining RRI, from 1997 to 2007 he served as vice chair of a department of internal medicine at an academic teaching hospital in Graz, Austria. Prior to moving to Graz in 1989, he worked from 1982 to 1989 in the Department of Physiology and the University Clinic of Internal Medicine in Innsbruck, Austria. From 1995 to 1996 he trained in nephrology at the Hammersmith Hospital, London, United Kingdom.