In patients with chronic kidney disease not on dialysis, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) slow the progression of diabetic nephropathy and reduce cardiovascular (CV) risk. However, data on their effectiveness in patients undergoing peritoneal dialysis (PD) are limited. Objectives: The objective of this observational study is to assess the relationship among ACEI or ARB use, preservation of residual renal function (RRF), and CV outcomes and death (cause specific and all-cause) in patients initiating PD. We will further explore any potential inter-clas differences in the association between ACEI vs. ARB use and these outcomes.
Our first aim i s to assess potential correlates of ACEI or ARB use. Candidate factors include demographic characteristics, concurrent co-morbid conditions, dialysis characteristics, and provider factors.
Our second aim i s to define the association between ACEI or ARB use and preservation of RRF, which will be calculated as the average of the 24 hour creatinine and urea clearances. We hypothesize that ACEI or ARB use will be associated with better preservation of RRF. We will also examine whether known determinants of loss of RRF modify this association.
Our third aim i s to evaluate the associations among ACEI or ARB use and the risk of CV outcomes, including myocardial infarction, hospitalization for heart failure, and cardiac cause of death, and all-cause mortality. We hypothesize that use of ACEI or ARB will be associated with lower rates of these outcomes. We will additionally study whether RRF (any vs. none) modifies these associations. Methods: We will use 2 data sources: A) electronic medical records of DaVita, Inc., will contain update medication lists as well as detailed information on vital signs and laboratory measurements;B) the U.S. Renal Data System.
The first aim will employ modified multivariable Poisson regression to test for any cross-sectional associations at 90 days after dialysis initiatio between ACEI or ARB use and numerous candidate characteristics. For our second and third aims, we will use multivariable time-to-event analyses to assess the associations between ACEI or ARB use and the clinical events of interest. We will further employ advanced statistical methods, including propensity score techniques;marginal structural models;instrumental variable analyses;repeated measures regression;missing data analysis and imputation;and competing risk models. Significance: Our research will capitalize on an unusually large and detailed dataset of patients initiating PD. In light of limited evidence supporting the use of ACEI or ARB in patients undergoing PD, additional studies are sorely needed, especially based on cohorts of typical patients in usual care settings. Further, the size of the database will allow us to study relevant patient subgroups.

Public Health Relevance

Peritoneal dialysis is a life-saving treatment for many Americans with life-threatening end-stage renal disease. Results of our research may lead to routine use of a class of medication that has the potential to improve their health.

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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Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
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Shen, Jenny I; Saxena, Anjali B; Vangala, Sitaram et al. (2017) Renin-angiotensin system blockers and residual kidney function loss in patients initiating peritoneal dialysis: an observational cohort study. BMC Nephrol 18:196
Shen, Jenny I; Saxena, Anjali B; Montez-Rath, Maria E et al. (2017) Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis. Nephrol Dial Transplant 32:862-869
Shen, Jenny I; Saxena, Anjali B; Montez-Rath, Maria E et al. (2017) Comparative effectiveness of angiotensin receptor blockers vs. angiotensin-converting enzyme inhibitors on cardiovascular outcomes in patients initiating peritoneal dialysis. J Nephrol 30:281-288
Lenihan, Colin R; Montez-Rath, Maria E; Shen, Jenny I et al. (2015) Correlates and outcomes of warfarin initiation in kidney transplant recipients newly diagnosed with atrial fibrillation. Nephrol Dial Transplant 30:321-9
Shen, Jenny I; Montez-Rath, Maria E; Lenihan, Colin R et al. (2015) Outcomes After Warfarin Initiation in a Cohort of Hemodialysis Patients With Newly Diagnosed Atrial Fibrillation. Am J Kidney Dis 66:677-88
Shen, Jenny I; Montez-Rath, Maria E; Mitani, Aya A et al. (2014) Correlates and variance decomposition analysis of heparin dosing for maintenance hemodialysis in older US patients. Pharmacoepidemiol Drug Saf 23:515-25
Chang, Tara I; Montez-Rath, Maria E; Shen, Jenny I et al. (2014) Thienopyridine use after coronary stenting in low income patients enrolled in medicare part D receiving maintenance dialysis. J Am Heart Assoc 3:e001356
Shen, Jenny I; Mitani, Aya A; Winkelmayer, Wolfgang C (2014) Heparin use in hemodialysis patients following gastrointestinal bleeding. Am J Nephrol 40:300-7
Shen, Jenny I; Mitani, Aya A; Chang, Tara I et al. (2013) Use and safety of heparin-free maintenance hemodialysis in the USA. Nephrol Dial Transplant 28:1589-602
Shen, Jenny I; Mitani, Aya A; Saxena, Anjali B et al. (2013) Determinants of peritoneal dialysis technique failure in incident US patients. Perit Dial Int 33:155-66

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