Abstract
Diabetic patients with declining kidney function are at heightened risk for hypoglycemia. We sought to determine whether hypoglycemia-related hospitalizations in the interval before dialysis therapy initiation are associated with post-end-stage renal disease (ESRD) mortality among incident patients with ESRD with diabetes. Observational cohort study. US veterans from the national Veterans Affairs database with diabetes and chronic kidney disease transitioning to dialysis therapy from October 2007 to September2011. Hypoglycemia-related hospitalizations during the pre-ESRD period and antidiabetic medication regimens. The outcome of post-ESRD all-cause mortality was evaluated relative to pre-ESRD hypoglycemia. The outcome of pre-ESRD hypoglycemia-related hospitalization was evaluated relative to antidiabetic medication regimens. We examined whether theoccurrence and frequency of pre-ESRD hypoglycemia-related hospitalizations are associated with post-ESRD mortality using Cox regression models adjusted for case-mix covariates. In a subcohort of patients prescribed 0 to 2 oral antidiabetic drugs and/or insulin, we examined the 12 most commonly prescribed antidiabetic medication regimens and risk for pre-ESRD hypoglycemia-related hospitalization using logistic regression models adjusted for case-mix covariates. Among 30,156 patients who met eligibility criteria, the occurrence of pre-ESRD hypoglycemia-related hospitalization(s) was associated with higher post-ESRD mortality risk: adjusted HR (aHR), 1.25; 95% CI, 1.17-1.34 (reference group: no hypoglycemia hospitalization). Increasing frequency of hypoglycemia-related hospitalizations was independently associated with incrementally higher mortality risk: aHRs of 1.21 (95% CI, 1.12-1.30), 1.47 (95% CI, 1.19-1.82), and 2.07(95% CI, 1.46-2.95) for 1, 2, and 3 ormorehypoglycemia-related hospitalizations, respectively (reference group: no hypoglycemia hospitalization). Compared with patients who were prescribed neither oral antidiabetic drugs nor insulin, medication regimens that included sulfonylureas and/or insulin were associated with higher risk for hypoglycemia. Residual confounding cannot be excluded. Among incident patients with ESRD with diabetes, a dose-dependent relationship between frequency of pre-ESRD hypoglycemia-related hospitalizations and post-ESRD mortality was observed. Further study of diabetic management strategies that prevent hypoglycemia as patients with chronic kidney disease transition to ESRD are warranted.
Highlights
Rationale & Objective: Diabetic patients with declining kidney function are at heightened risk for hypoglycemia
We sought to determine whether hypoglycemia-related hospitalizations in the interval before dialysis therapy initiation are associated with post–end-stage renal disease (ESRD) mortality among incident patients with ESRD with diabetes
Increasing frequency of hypoglycemia-related hospitalizations was independently associated with incrementally higher mortality risk: adjusted HR (aHR) of 1.21, 1.47, and 2.07 for 1, 2, and 3 or more hypoglycemia-related hospitalizations, respectively
Summary
Source CohortWe conducted a historical cohort study with longitudinal data from the Transition of Care in CKD (TC-CKD) study, a retrospective cohort study examining US veterans transitioning to ESRD from October 1, 2007, to September 30, 2011.3,25-28 Our source population consisted of 52,172 patients who were identified from the national VA database and linked to the USRDS registry. Patients were included provided that they were 18 years or older at the time of entry into the VA health care system, had a history of diabetes ascertained by International Classification of Diseases, Ninth Revision (ICD-9) codes (249.xx, 250.xx, 357.2, 362.0x, and 366.41) before dialysis therapy initiation and/or cause of ESRD due to diabetes, had no missing data for core variables needed to calculate estimated glomerular filtration rate (eGFR), and initiated dialysis therapy before study entry or after exiting the study (Fig S1). Given that a core objective of the TC-CKD study is to determine the impact of pre-ESRD comorbid conditions on post-ESRD outcomes, we a priori defined the more than 1- to 2-year prelude period as our primary exposure window during which potential interventions informed by the present study can have greater impact on post-ESRD outcomes The CKDEPI (CKD Epidemiology Collaboration) creatinine equation was used to calculate eGFR.[39]
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