Cystatin C as a risk factor for outcomes in chronic kidney disease

Ann Intern Med. 2007 Jul 3;147(1):19-27. doi: 10.7326/0003-4819-147-1-200707030-00004.


Background: No study has compared cystatin C level, serum creatinine concentration, and estimated glomerular filtration rate (GFR) as risk factors for outcomes in chronic kidney disease (CKD), and none has compared measured GFR with CKD in any population.

Objective: To compare cystatin C level with serum creatinine concentration and iothalamate GFR as risk factors for death and kidney failure.

Design: Observational study using serum cystatin C assayed from baseline samples of the Modification of Diet in Renal Disease Study (1989-1993).

Setting: 15 clinical centers in the United States that participated in the Modification of Diet in Renal Disease Study.

Participants: 825 trial participants with stage 3 or 4 nondiabetic CKD who had measurements of serum cystatin C.

Measurements: All-cause mortality, cardiovascular (CVD) mortality, and kidney failure until December 2000.

Results: Mean cystatin C level, creatinine concentration, and GFR were 2.2 mg/L (SD, 0.7), 212.16 micromol/L (SD, 88.4) (2.4 mg/dL [SD, 1.0]), and 33 mL/min per 1.73 m2 (SD, 12), respectively. Median follow-up was 10 years. Twenty-five percent of patients (n = 203) died of any cause, 15% (n = 123) died of CVD, and 66% (n = 548) reached kidney failure. In multivariate-adjusted models, 1-SD decreases in 1/creatinine, GFR, and 1/cystatin C were associated with increased risks for all-cause mortality of 1.27 (95% CI, 1.06 to 1.49), 1.27 (CI, 1.08 to 1.49), and 1.41 (CI, 1.18 to 1.67), respectively. For CVD mortality, the increased risks were 1.32 (CI, 1.05 to 1.64), 1.28 (CI, 1.04 to 1.59), and 1.64 (CI, 1.28 to 2.08), respectively. For kidney failure, the increased risks were 2.81 (CI, 2.48 to 3.18), 2.41 (CI, 2.15 to 2.70), and 2.36 (CI, 2.10 to 2.66), respectively.

Limitation: The Modification of Diet in Renal Disease Study cohort may not be representative of all patients with nondiabetic CKD because participants were more likely to reach kidney failure than death in follow-up.

Conclusion: The association of cystatin C level with all-cause and CVD mortality was as strong as or perhaps stronger than that of iothalamate GFR with these outcomes in stage 3 or 4 CKD.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cardiovascular Diseases / mortality*
  • Chronic Disease
  • Creatinine / blood*
  • Cystatin C
  • Cystatins / blood*
  • Glomerular Filtration Rate*
  • Humans
  • Kidney Diseases / physiopathology*
  • Middle Aged
  • Mortality
  • Renal Insufficiency / etiology*
  • Risk Factors
  • Sensitivity and Specificity


  • CST3 protein, human
  • Cystatin C
  • Cystatins
  • Creatinine