Variation of serum creatinine, cystatin C, and creatinine clearance tests in persons with normal renal function

Clin Chim Acta. 2008 Sep;395(1-2):115-9. doi: 10.1016/j.cca.2008.05.020. Epub 2008 Jun 3.


Background: To determine the potential sensitivity of several renal function tests for detecting early changes in renal function, we compared the within-individual (W-I) variation over 5 months of serum creatinine, serum cystatin C, and creatinine clearance.

Methods: On 31 healthy subjects, blood and timed urine specimens were collected once each month to get 6 collections. Creatinine (enzymatic) in serum and urine and cystatin C (immunonephelometric) in serum were measured and glomerular filtration rate (GFR) by creatinine clearance and the Modification of Diet in Renal Disease (MDRD) equation were calculated. To compare W-I variations between different creatinine methods, we also measured creatinine by both enzymatic and kinetic alkaline picrate methods on 15 sets of frozen samples.

Results: For the 31 volunteers, the mean W-I variations for serum creatinine (5.8%) and cystatin C (5.4%) were both much lower than the W-I variation of creatinine clearance (18.7%). As expected, the MDRD GFR had a similar W-I variation (6.7%) to that of serum creatinine and its values were markedly different than GFR by creatinine clearance. On the 15 sets of frozen samples, the W-I variation of creatinine measured by the enzymatic method (CV 5.2%) was slightly less than by the picrate method (CV 6.2%).

Conclusions: The low W-I variation of both serum cystatin C and serum creatinine suggests that serial measurements of either would detect a changes in renal function earlier than would GFR by creatinine clearance or MDRD equation, which allows reporting only for GFRs<60 ml/min/1.7 m(2). While we measured only creatinine clearance, the large variability, difficulty, and cost of all clearance measurements make them impractical for routine monitoring of patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Creatinine / blood*
  • Creatinine / metabolism*
  • Creatinine / urine
  • Cystatin C
  • Cystatins / blood*
  • Cystatins / metabolism
  • Cystatins / urine
  • Female
  • Glomerular Filtration Rate*
  • Humans
  • Male
  • Middle Aged
  • Reference Values
  • Reproducibility of Results
  • Sensitivity and Specificity


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