Cystatin C

2016, Volume 26, Number 1


Richard S. Bak, Ph.D.,
Director of Laboratory Operations, Warde Medical Laboratory

Cystatin C is a low molecular weight protein synthesized by all nucleated cells. It is an inhibitor of cysteine protease.

Cystatin C has a constant rate of endogenous production, is freely filtered by the glomerulus, and has no extrarenal excretion making it a very useful marker for glomerular filtration rate (GFR). In patients with impaired GFR, the serum level of cystatin C increases.

A number of studies have compared creatinine versus serum cystatin C as an indicator of renal function, and the general consensus is that cystatin C is better than creatinine in correlating with the true GFR (1). In a group of patients with a range of GFRs, the cystatin C concentration increased sooner than the creatinine as GFR declined.

Cystatin C concentrations started to increase as GFR fell below about 80 mls/min/1.73m2 compared with about 40 mls /min/1.73m2 for serum creatinine (2). Cystatin C is therefore especially useful when trying to determine mild to moderate impairment of kidney function (3, 4).

The serum concentration of cystatin C remains unchanged with infections, inflammatory or neoplastic states, and is not affected by body mass, diet, or gender (5). Its concentration is also not influenced by analytical interferences like bilirubin and hemoglobin, as is creatinine. These are common challenges in pediatric samples due to neonatal jaundice and in vitro hemolysis occurring during pediatric sample collection.

Other conditions where cystatin C may provide more accurate assessment of GFR than creatinine include the very obese, elderly, or malnourished patients. However, several publications suggest an influence of thyroid hormone (6,7,8.

With the emergence of GFR as the primary criterion in the classification of chronic kidney disease (9), there is an increased interest among nephrologists, and other clinicians, for a more accurate estimate of GFR. Cystatin C, although not a perfect marker, has proven to be superior to serum creatinine or creatinine clearance.

Cystatin C is now performed at Warde Medical Laboratory Sunday through Friday with a turnaround time of one to two days. Order test code CYSTC.


  1. Price CP, Finney H. Developments in the assessment of glomerular filtration rate. Clin Chem A eta 2000; 297:55-66
  2. Newman DJ, Thakkar H, Edwards RG, Wilkie M, White T, Grubb AO, et al. Serum cystatin C measured by automated immunoassay: a more sensitive marker of changes in GFR than serum creatinine. Kidney Int 1995; 47:312-8.
  3. Boston AG, D workin LD. Cystatin C measurement: improved detection of mild decrements in glomerular filtration rates versus creatinine – based estimates? Am J Kidney D is 2000; 36:205-7.
  4. Coll E, Botney A, Alvarey L, Poch E, Quinto L, Saurina A, et al. Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment. Am J. Kidney Dis 2000; 36:29-34.
  5. Kyhse – Andersen J, Schmidt C, Nordin G, Andersson B, Wilsson – Ehle P, Lindstrom V, et al. Serum cystatin C, determined by a rapid, automated particle – enhanced turbid metric method, is a better marker than serum creatinine for glomerular filtration rate. Clin Chem 1994; 40: 1921-6.
  6. Den Hollander JG, Wulkan RW, Mantel MJ, Berghout A. Is cystatin C a marker of glomerular filtration rate in thyroid dysfunction? Clin Chem 2003; 49:1558-9.
  7. Frickser M, Wiesli P, Brandle M, Schwegler B, Schmid C. Impact of thyroid dysfunction on serum cystatin C. Kidney Int 2003; 63:1944-7.
  8. Jayagopal V, Keevil BG, Atkin SL, Jennings PE, Kilpatrick ES. Paradoxical changes in cystatin C and serum creatinine in patients with hypo- and hyperthyroidism. Clin Chem 2003;49:680-1
  9. Levey AS, Eckardt KU, Tsukamoto Y, et al. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005; 67:2089-100.