Hypoglycemia-Related Hospitalizations and Mortality Among Patients With Diabetes Transitioning to Dialysis

Connie M. Rhee, Csaba Kovesdy, Amy S. You, John J. Sim, Melissa Soohoo, Elani Streja, Miklos Z. Molnar, Alpesh N. Amin, Kevin Abbott, Danh V. Nguyen, Kamyar Kalantar-Zadeh

Research output: Contribution to journalArticle

Abstract

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. Study Design: Observational cohort study. Setting & Participants: US veterans from the national Veterans Affairs database with diabetes and chronic kidney disease transitioning to dialysis therapy from October 2007 to September 2011. Exposure: Hypoglycemia-related hospitalizations during the pre-ESRD period and antidiabetic medication regimens. Outcome: 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. Analytic Approach: We examined whether the occurrence 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. Results: 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 or more hypoglycemia-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. Limitations: Residual confounding cannot be excluded. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)701-710
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume72
Issue number5
DOIs
StatePublished - Nov 1 2018

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Hypoglycemia
Chronic Kidney Failure
Dialysis
Hospitalization
Mortality
Hypoglycemic Agents
Diagnosis-Related Groups
Veterans
Insulin
Chronic Renal Insufficiency
Logistic Models
Kidney
Proportional Hazards Models
Observational Studies
Cohort Studies

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Hypoglycemia-Related Hospitalizations and Mortality Among Patients With Diabetes Transitioning to Dialysis. / Rhee, Connie M.; Kovesdy, Csaba; You, Amy S.; Sim, John J.; Soohoo, Melissa; Streja, Elani; Molnar, Miklos Z.; Amin, Alpesh N.; Abbott, Kevin; Nguyen, Danh V.; Kalantar-Zadeh, Kamyar.

In: American Journal of Kidney Diseases, Vol. 72, No. 5, 01.11.2018, p. 701-710.

Research output: Contribution to journalArticle

Rhee, CM, Kovesdy, C, You, AS, Sim, JJ, Soohoo, M, Streja, E, Molnar, MZ, Amin, AN, Abbott, K, Nguyen, DV & Kalantar-Zadeh, K 2018, 'Hypoglycemia-Related Hospitalizations and Mortality Among Patients With Diabetes Transitioning to Dialysis', American Journal of Kidney Diseases, vol. 72, no. 5, pp. 701-710. https://doi.org/10.1053/j.ajkd.2018.04.022
Rhee, Connie M. ; Kovesdy, Csaba ; You, Amy S. ; Sim, John J. ; Soohoo, Melissa ; Streja, Elani ; Molnar, Miklos Z. ; Amin, Alpesh N. ; Abbott, Kevin ; Nguyen, Danh V. ; Kalantar-Zadeh, Kamyar. / Hypoglycemia-Related Hospitalizations and Mortality Among Patients With Diabetes Transitioning to Dialysis. In: American Journal of Kidney Diseases. 2018 ; Vol. 72, No. 5. pp. 701-710.
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abstract = "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. Study Design: Observational cohort study. Setting & Participants: US veterans from the national Veterans Affairs database with diabetes and chronic kidney disease transitioning to dialysis therapy from October 2007 to September 2011. Exposure: Hypoglycemia-related hospitalizations during the pre-ESRD period and antidiabetic medication regimens. Outcome: 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. Analytic Approach: We examined whether the occurrence 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. Results: 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 or more hypoglycemia-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. Limitations: Residual confounding cannot be excluded. Conclusions: 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.",
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T1 - Hypoglycemia-Related Hospitalizations and Mortality Among Patients With Diabetes Transitioning to Dialysis

AU - Rhee, Connie M.

AU - Kovesdy, Csaba

AU - You, Amy S.

AU - Sim, John J.

AU - Soohoo, Melissa

AU - Streja, Elani

AU - Molnar, Miklos Z.

AU - Amin, Alpesh N.

AU - Abbott, Kevin

AU - Nguyen, Danh V.

AU - Kalantar-Zadeh, Kamyar

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N2 - 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. Study Design: Observational cohort study. Setting & Participants: US veterans from the national Veterans Affairs database with diabetes and chronic kidney disease transitioning to dialysis therapy from October 2007 to September 2011. Exposure: Hypoglycemia-related hospitalizations during the pre-ESRD period and antidiabetic medication regimens. Outcome: 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. Analytic Approach: We examined whether the occurrence 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. Results: 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 or more hypoglycemia-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. Limitations: Residual confounding cannot be excluded. Conclusions: 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.

AB - 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. Study Design: Observational cohort study. Setting & Participants: US veterans from the national Veterans Affairs database with diabetes and chronic kidney disease transitioning to dialysis therapy from October 2007 to September 2011. Exposure: Hypoglycemia-related hospitalizations during the pre-ESRD period and antidiabetic medication regimens. Outcome: 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. Analytic Approach: We examined whether the occurrence 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. Results: 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 or more hypoglycemia-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. Limitations: Residual confounding cannot be excluded. Conclusions: 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.

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