title: Creatinine excretion rate and mortality in type 2 diabetes and nephropathy.
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.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Steef J
authors.initials: SJ
authors.lastname: Sinkeler
authors.forename: Arjan J
authors.initials: AJ
authors.lastname: Kwakernaak
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Shahinfar
authors.forename: Enric
authors.initials: E
authors.lastname: Esmatjes
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Hiddo J
authors.initials: HJ
authors.lastname: Lambers Heerspink
mesh_terms: D000368:Aged; D003404:Creatinine / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000401:mortality*; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000401:mortality*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D003404:Creatinine