Creatinine Excretion Rate and Mortality in Type 2 Diabetes and Nephropathy

Steef J. Sinkeler, MD, Arjan J. Kwakernaak, MD, Stephan J.L. Bakker, MD, PHD, Shahnaz Shahinfar, MD, PHD, Enric Esmatjes, MD, PHD,
Dick de Zeeuw, MD, PHD, Gerjan Navis, MD, PHD, Hiddo J. Lambers and
Heerspink, PHARMD, PHD

Published online before print January 8, 2013, doi: 10.2337/dc12-1545 Diabetes Care January 8, 2013

Abstract

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.