Creatinine Excretion Rate and Mortality in Type 2 Diabetes and Nephropathy

• Published in: Diabetes care Vol. 36; no. 6; pp. 1489 - 1494
• Main Authors: Sinkeler, Steef J., Kwakernaak, Arjan J., Bakker, Stephan J.L., Shahinfar, Shahnaz, Esmatjes, Enric, de Zeeuw, Dick, Navis, Gerjan, Lambers Heerspink, Hiddo J.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.06.2013
• Subjects: Aged; Angiotensin; Biological and medical sciences; Cholesterol; Creatinine - metabolism; Diabetes; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - mortality; Diabetes. Impaired glucose tolerance; Diabetic nephropathies; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - mortality; Diet; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Health aspects; Humans; Insulin resistance; Kidney diseases; Male; Medical sciences; Metabolic diseases; Middle Aged; Miscellaneous; Mortality; Multivariate analysis; Original Research; Public health. Hygiene; Public health. Hygiene-occupational medicine; Regression analysis; Studies; Type 2 diabetes; Endocrinopathy; Kidney disease; Creatinine; Type 2 diabetes; Human; Excretion; Urinary system disease; Nutrition; Mortality; Rate; Metabolic diseases; Epidemiology; Nephropathy; Endocrinology
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc12-1545

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. We used data from the combined Reduction of Endpoints in Non-insulin 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. 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. 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.