Changes in dietary protein intake has no effect on serum cystatin C levels independent of the glomerular filtration rate

Kidney Int. 2011 Feb;79(4):471-7. doi: 10.1038/ki.2010.431. Epub 2010 Oct 27.


Cystatin C is being considered as a replacement for serum creatinine in the estimation of the glomerular filtration rate (GFR); however, its plasma levels might be affected by factors other than the GFR, such as protein intake. We performed a post hoc analysis of the data in the Modification of Diet in Renal Disease study, in which we compared serum creatinine and cystatin C levels in 741 patients with available estimates of protein intake at baseline prior to their randomization to diets containing various amounts of protein, and at 2 years of follow-up in 426 of these patients in whom a cystatin C measurement was available. The 503 patients in study A (GFR 25-55 ml/min per 1.73 m(2)) had been assigned a low (0.58 g/kg per day) or a usual (1.3 g/kg per day) protein intake, and the 238 participants in study B (GFR 13-24 ml/min per 1.73 m(2)) were assigned a very low (0.28 g/kg per day) or the low protein intake. In either study group, lowering the dietary protein intake reduced the change in creatinine, but did not have a significant change in cystatin C. Thus, in patients with moderate-to-severe chronic kidney disease, serum cystatin C unlike serum creatinine was not affected by dietary protein intake independent of changes in GFR. Hence, cystatin C may allow more accurate estimates of GFR than creatinine for patients with reduced protein intake. Further study of other non-GFR determinants of cystatin C is needed before the widespread adoption.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Creatinine / blood
  • Cross-Sectional Studies
  • Cystatin C / blood*
  • Dietary Proteins / administration & dosage*
  • Female
  • Glomerular Filtration Rate / physiology*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / diet therapy
  • Renal Insufficiency, Chronic / physiopathology
  • Young Adult


  • Biomarkers
  • CST3 protein, human
  • Cystatin C
  • Dietary Proteins
  • Creatinine