Connie M Rhee1, Csaba P Kovesdy2,3, Vanessa A Ravel4, Elani Streja4, Steven M Brunelli5, Melissa Soohoo4, Keiichi Sumida2,3, Miklos Z Molnar2,6, Gregory A Brent7,8, Danh V Nguyen9, Kamyar Kalantar-Zadeh1. 1. Harold Simmons Center for Chronic Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA kkz@uci.edu crhee1@uci.edu. 2. Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN. 3. Nephrology Section, Memphis Veterans Affairs Medical Center, Memphis, TN. 4. Harold Simmons Center for Chronic Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA. 5. DaVita Clinical Research, Minneapolis, MN. 6. Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary. 7. Division of Endocrinology, Diabetes and Hypertension, David Geffen School of Medicine at UCLA, Los Angeles, CA. 8. Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA. 9. Division of General Internal Medicine, University of California Irvine, Orange, CA.
Abstract
OBJECTIVE: Although early trials suggested that intensive glycemic targets reduce the number of complications with diabetes, contemporary trials indicate no cardiovascular benefit and potentially higher mortality risk. As patients with advanced chronic kidney disease (CKD) transitioning to treatment with dialysis were excluded from these studies, the optimal glycemic level in this population remains uncertain. We hypothesized that glycemic status, defined by hemoglobin A1c (HbA--1c) and random glucose levels, in the pre-end-stage renal disease (ESRD) period is associated with higher 1-year post-ESRD mortality among patients with incident diabetes who have ESRD. RESEARCH DESIGN AND METHODS: Among 17,819 U.S. veterans with diabetic CKD transitioning to dialysis from October 2007 to September 2011, we examined the association of mean HbA--1c and random glucose levels averaged over the 1-year pre-ESRD transition period with mortality in the first year after dialysis initiation. All-cause mortality hazard ratios (HRs) were estimated using multivariable survival models. Secondary analyses examined cardiovascular mortality using competing risks methods. RESULTS: HbA--1c levels ≥8% (≥64 mmol/mol) were associated with higher mortality in the first year after dialysis initiation (reference value 6% to <7% [42-53 mmol/mol]): adjusted HRs [aHRs] 1.19 [95% CI 1.07-1.32] and 1.48 (1.31-1.67) for HbA--1c 8% to <9% [64-75 mmol/mol] and ≥9% [≥75 mmol/mol], respectively). Random glucose levels ≥200 mg/dL were associated with higher mortality (reference value 100 to <125 mg/dL): aHR 1.34 [95% CI 1.20-1.49]). Cumulative incidence curves showed that incrementally higher mean HbA--1c and random glucose levels were associated with increasingly higher cardiovascular mortality. CONCLUSIONS: In patients with diabetes and CKD transitioning to dialysis, higher mean HbA--1c and random glucose levels during the pre-ESRD prelude period were associated with higher 1-year post-ESRD mortality. Clinical trials are warranted to examine whether modulating glycemic status improves survival in this population.
OBJECTIVE: Although early trials suggested that intensive glycemic targets reduce the number of complications with diabetes, contemporary trials indicate no cardiovascular benefit and potentially higher mortality risk. As patients with advanced chronic kidney disease (CKD) transitioning to treatment with dialysis were excluded from these studies, the optimal glycemic level in this population remains uncertain. We hypothesized that glycemic status, defined by hemoglobin A1c (HbA--1c) and random glucose levels, in the pre-end-stage renal disease (ESRD) period is associated with higher 1-year post-ESRD mortality among patients with incident diabetes who have ESRD. RESEARCH DESIGN AND METHODS: Among 17,819 U.S. veterans with diabetic CKD transitioning to dialysis from October 2007 to September 2011, we examined the association of mean HbA--1c and random glucose levels averaged over the 1-year pre-ESRD transition period with mortality in the first year after dialysis initiation. All-cause mortality hazard ratios (HRs) were estimated using multivariable survival models. Secondary analyses examined cardiovascular mortality using competing risks methods. RESULTS: HbA--1c levels ≥8% (≥64 mmol/mol) were associated with higher mortality in the first year after dialysis initiation (reference value 6% to <7% [42-53 mmol/mol]): adjusted HRs [aHRs] 1.19 [95% CI 1.07-1.32] and 1.48 (1.31-1.67) for HbA--1c 8% to <9% [64-75 mmol/mol] and ≥9% [≥75 mmol/mol], respectively). Random glucose levels ≥200 mg/dL were associated with higher mortality (reference value 100 to <125 mg/dL): aHR 1.34 [95% CI 1.20-1.49]). Cumulative incidence curves showed that incrementally higher mean HbA--1c and random glucose levels were associated with increasingly higher cardiovascular mortality. CONCLUSIONS: In patients with diabetes and CKD transitioning to dialysis, higher mean HbA--1c and random glucose levels during the pre-ESRD prelude period were associated with higher 1-year post-ESRD mortality. Clinical trials are warranted to examine whether modulating glycemic status improves survival in this population.
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