Creatinine Excretion Rate and Mortality in Type 2 Diabetes and Nephropathy
- Steef J. Sinkeler, MD1,
- Arjan J. Kwakernaak, MD1,
- Stephan J.L. Bakker, MD, PHD1,
- Shahnaz Shahinfar, MD, PHD2,
- Enric Esmatjes, MD, PHD3,
- Dick de Zeeuw, MD, PHD4,
- Gerjan Navis, MD, PHD1⇓,
- Hiddo J. Lambers and
- Heerspink, PHARMD, PHD4
- 1Division of Nephrology, Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- 2The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
- 3Hospital Clinico y Provincial, Barcelona, Spain
- 4Department of Clinical Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Corresponding author: Gerjan Navis, .
S.J.S. and A.J.K. contributed equally to this study.
OBJECTIVE The creatinine excretion rate (CER) is inversely associated with mortality in the general and renal transplant population. The CER is a marker for muscle mass. It is unknown whether the CER is associated with outcome in diabetes. We therefore investigated whether the CER is a determinant of all-cause mortality in diabetic patients.
RESEARCH DESIGN AND METHODS We used data from the combined Reduction of End Points in Noninsulin-Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) and Irbesartan Diabetic Nephropathy Trial (IDNT) studies. A total of 1,872 patients (58% of the overall population) with type 2 diabetes and nephropathy with valid 24-h urinary creatinine excretion data were included. The primary end point of the analyses was all-cause mortality.
RESULTS Mean age was 60 ± 8 years and median CER was 1,407 (total range 400–3,406) mg/day. Body surface area, hemoglobin, black race, and albuminuria were positive independent determinants of the CER, whereas female sex and age were inverse independent determinants of the CER. During a median follow-up of 36 (29–45) months, 300 patients died. In a Kaplan-Meier analysis of sex-stratified tertiles of the CER, risk for all-cause mortality increased with decreasing CER (P < 0.001). In a multivariable Cox regression analysis, lower CER (as a continuous variable) was independently associated with increased risk for all-cause mortality (hazard ratio 0.39 [95% CI 0.29–0.52], P < 0.001). Adjustment for potential collection errors did not materially change these associations.
CONCLUSIONS Lower CER was strongly associated with increased all-cause mortality in patients with type 2 diabetes and nephropathy. As the CER can be considered a proxy for muscle mass, this puts renewed emphasis on physical condition and exercise in this population.
- Received August 1, 2012.
- Accepted December 5, 2012.
- © 2013 by the American Diabetes Association.
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