There are over 350,000 maintenance thrice-weekly hemodialysis patients in the United States. These patients have exceptionally poor survival with mortality rates exceeding those of the general population by greater than 10-fold. Prior research has suggested that modifications in dialytic practice such as gentler ultrafiltration rates (UFR) may improve survival. UFR is determined by both the amount of fluid that must be removed (which at steady state equals the inter-dialytic weight gain;IDWG) and the time over which this fluid is removed (dialysis session length;DSL), each of which are plausibly associated with mortality. This project seeks to elucidate the independent associations between DSL and IDWG and mortality. A matched, retrospective cohort analysis of a nationally representative population of prevalent chronic, thrice weekly hemodialysis patients (n= 10,000) with follow-up time of 5 years will be used to: 1) estimate the association between IDWG and mortality, independent of DSL, through analysis of matched pairs of participants with discordant IDWG but identical DSL, and 2) estimate the association between DSL and mortality, independent of IDWG, through analysis of matched pairs of participants with discordant DSL but identical IDWG. A matched study design has been chosen to allow for complete control of DSL in analyses of IDWG and for IDWG in analyses of DSL to enable accurate estimation of the independent association of each with survival. Findings will inform modifications to clinical practice and direct future research. In addition to understanding the independent relationships of DSL and IDWG and mortality, the project will assess patients'willingness to adopt interventions aimed at improving health and survival through targeted manipulations of fluid management. No prior research has assessed patient willingness to extend DSL in response to volume considerations within the context of thrice weekly dialysis. Other untested methods of IDWG control including interdialytic peritoneal dialysis and wearable ultrafiltration devices do exist. An instrument will be developed and validated to assess patient willingness to adhere to fluid/salt restrictions, adopt adjunct interdialytic peritoneal dialysis, utilize wearable ultrafiltration devices, and extend DSL as methods to minimize need for rapid UFR. This instrument will then be used to survey attitudes of 5,000 randomly selected hemodialysis outpatients from the End Stage Renal Disease Network of New England. Responses will inform clinical practice and guide future research in volume mitigation.

Public Health Relevance

Dialysis patients experience an extremely high burden of mortality. This project seeks to elucidate how aggressive ultrafiltration rates increase mortality by examining the independent relationships of mortality and dialysis session length and mortality and interdialytic weight gain. Additionally, the project seeks to understand dialysis patient willingness to engage in different volume mitigation strategies. Results will guide clinical practice and future research by identifying ways in which the dialytic prescription can be modified to improve mortality.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZDK1-GRB-G (M1))
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Rankin, Tracy L
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Brigham and Women's Hospital
United States
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Flythe, Jennifer E; Mangione, Thomas W; Brunelli, Steven M et al. (2014) Patient-stated preferences regarding volume-related risk mitigation strategies for hemodialysis. Clin J Am Soc Nephrol 9:1418-25
Flythe, Jennifer E; Curhan, Gary C; Brunelli, Steven M (2013) Disentangling the ultrafiltration rate-mortality association: the respective roles of session length and weight gain. Clin J Am Soc Nephrol 8:1151-61
Flythe, Jennifer E; Curhan, Gary C; Brunelli, Steven M (2013) Shorter length dialysis sessions are associated with increased mortality, independent of body weight. Kidney Int 83:104-13
Flythe, Jennifer E; Inrig, Jula K; Shafi, Tariq et al. (2013) Association of intradialytic blood pressure variability with increased all-cause and cardiovascular mortality in patients treated with long-term hemodialysis. Am J Kidney Dis 61:966-74
Flythe, Jennifer E; Lacson Jr, Eduardo (2012) Outcomes after the long interdialytic break: implications for the dialytic prescription. Semin Dial 25:1-8