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Glycosylated Hemoglobin and Mortality in Patients with Nondiabetic Chronic Kidney Disease

Vandana Menon^*, Tom Greene, Arema A. Pereira^*, Xuelei Wang, Gerald J. Beck, John W. Kusek, Allan J. Collins, Andrew S. Levey^* and Mark J. Sarnak^*

^* Department of Medicine, Division of Nephrology, Tufts-New England Medical Center, Boston, Massachusetts, Department of Biostatistics and Epidemiology, Cleveland Clinic Foundation, Cleveland, Ohio, National Institutes of Health, Bethesda, Maryland, and Division of Nephrology, Hennepin County Medical Center, Minneapolis, Minnesota

Address correspondence to: Dr. Mark Sarnak, Division of Nephrology, Department of Medicine, 750 Washington Street, NEMC #391, Boston, MA 02111. Phone: 617-636-1182; Fax: 617-636-8329; E-mail: msarnak{at}tufts-nemc.org

Received for publication May 26, 2005. Accepted for publication August 30, 2005.

In the general population, hyperglycemia in the absence of diabetes may be associated with increased risk for mortality. Hyperglycemia is prevalent in chronic kidney disease; however, the relationship between glycosylated hemoglobin (HbA_1c) as a marker of chronic hyperglycemia and outcomes has not been studied in nondiabetic chronic kidney disease. HbA_1c was measured at baseline in the randomized cohort of the Modification of Diet in Renal Disease Study (n = 840). Participants with diabetes (n = 43), fasting glucose levels >126 mg/dl (n = 20), or missing HbA_1c levels (n = 9) were excluded. Survival status until December 2000 was obtained from the National Death Index. Death was classified as cardiovascular (CVD) when the primary cause was International Classification of Disease, Ninth Revision codes 390 to 459. Cox models were performed to assess the relationship of HbA_1c with all-cause and CVD mortality. Mean (SD) age was 52 (12) years, and mean (SD) GFR was 32 (12) ml/min per 1.73 m². Eighty-six percent of participants were white, and 61% were male. Mean (SD) HbA_1c was 5.6% (0.5). A total of 169 (22%) patients died, 96 (13%) from CVD. After adjustment for randomization assignments and demographic, CVD, and kidney disease factors, HbA_1c was a predictor of all-cause mortality (hazard ratio per 1% increase 1.73; 95% confidence interval 1.24 to 2.41; P = 0.001). There was a trend toward statistical significance in the relationship between HbA_1c and CVD mortality (hazard ratio per 1% increase 1.53; 95% confidence interval 0.96 to 2.43; P = 0.07). HbA_1c is associated with increased mortality in nondiabetic kidney disease. Hyperglycemia may be a potential therapeutic target and HbA_1c may be important as a risk stratification tool in this high-risk population.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673