Serum Concentration of Cystatin C and Risk of End-Stage Renal Disease in Diabetes

  1. Per-Henrik Groop, MD, DMSC3,4
  1. 1Research and Clinic Divisions, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
  2. 2Department of Medicine, Brigham and Women′s Hospital, Harvard Medical School, Boston, Massachusetts
  3. 3Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
  4. 4Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
  5. 5Renal Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
  6. 6Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota
  7. 7Division of Nephrology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts
  1. Corresponding author: Andrzej S. Krolewski, andrzej.krolewski{at}


OBJECTIVE Patients with diabetes have a high risk of end-stage renal disease (ESRD). We examined whether prediction of this outcome, according to chronic kidney disease (CKD) staging by creatinine-based estimates of the glomerular filtration rate (eGFRcreat), is improved by further staging with serum cystatin C–based estimates (eGFRcyst).

RESEARCH DESIGN AND METHODS Patients with diabetes in CKD stages 1–3 were selected from three cohorts: two from Joslin Diabetes Center, one with type 1 diabetes (N = 364) and one with type 2 diabetes (N = 402), and the third from the Finnish Diabetic Nephropathy (FinnDiane) Study of type 1 (N = 399). Baseline serum concentrations of creatinine and cystatin C were measured in all patients. Follow-up averaged 8–10 years and onsets of ESRD (n = 246) and death unrelated to ESRD (n = 159) were ascertained.

RESULTS Although CKD staging by eGFRcyst was concordant with that by eGFRcreat for 62% of Joslin patients and 73% of FinnDiane patients, those given a higher stage by eGFRcyst than eGFRcreat had a significantly higher risk of ESRD than those with concordant staging in all three cohorts (hazard ratio 2.3 [95% CI 1.8–3.1]). Similarly, patients at a lower stage by eGFRcyst than by eGFRcreat had a lower risk than those with concordant staging (0.30 [0.13–0.68]). Deaths unrelated to ESRD followed the same pattern, but differences were not as large.

CONCLUSIONS In patients with diabetes, CKD staging based on eGFRcyst significantly improves ESRD risk stratification based on eGFRcreat. This conclusion can be generalized to patients with type 1 and type 2 diabetes and to diabetic patients in the U.S. and Finland.


  • Received November 15, 2011.
  • Accepted May 7, 2012.

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