Cleveland Clinic Laboratories

Technical Brief Cystatin C as an Indicator of Renal Function

Background Information Cystatin C is a cysteine proteinase inhibitor with a molecular Because cystatin C is less affected by confounding factors than weight of 13,250 daltons that is produced by all nucleated is creatinine, it may be a more useful indicator of renal status cells. It is formed at a constant rate and freely filtered by the in patients with normal or near-normal function. Studies kidney before being resorbed and degraded by the renal have shown that serum cystatin C concentrations are superior tubular cells. Therefore, cystatin C is an excellent indicator to creatinine for detection of early renal failure (1,2). This of glomerular filtration rate (GFR). relationship may provide the basis for its use as an outcome

Serum concentrations of cystatin C depend exclusively on predictor in patients with cardiac disease and others (3-5). glomerular filtration rate and are not affected by factors known Clinical Indications to affect serum creatinine values, including muscle mass, Serum cystatin C can be used to assess renal function (2) gender, or nutrition. The relationships of cystatin C to creatinine and to determine adverse outcome risk in patients with acute and to the GFR are shown below. coronary syndromes (3), peripheral artery disease (4), and in the elderly (5).

Interpretation Reference interval for individuals without renal dysfunction: < 65 years of age: 0.50 – 1.12 mg/L > 65 years of age: 0.55 – 1.21 mg/L.

Values >1.25 mg/L are indicative of a GFR < 58 mL/min. In patients with acute coronary syndromes, values > 1.25 mg/L demonstrated a relative risk for death of 11.7 compared with those whose value was < 0.83 mg/L (3).

Elderly individuals with values > 1.29 mg/L exhibited a hazard ratio of 2.27 for death from cardiovascular causes (5).

Limitations of the Assay Cystatin C should not necessarily be used as sole indicator for renal disease. The National Kidney Foundation recommends that the presence of chronic kidney disease be determined by estimating the GFR using the modified MDRD equation and an IDMS-traceable creatinine measurement and not reporting of values greater than 60 mL/min.

Specimens with significant lipemia are not suitable for analysis, and clarification by ultra-centrifugation is necessary prior to testing. Specimens should be stored no longer than seven days refrigerated. If frozen within 24 hours of collection, specimens are stable for up to three months. Cleveland Clinic Laboratories 9500 Euclid Avenue, L15, Cleveland, Ohio 44195 800.628.6816 | clevelandcliniclabs.com

Methodology Cystatin C is measured with a particle-enhanced immuno- they bind cystatin C in the specimen. These aggregates scatter turbidometric assay (PETIA) that utilizes polystyrene particles light to a degree proportional to the cystatin C concentration. coated with antibodies specific for cystatin C. When mixed Comparison of the amount of light lost to scatter to a standard with serum these antibody-coated particles aggregate when curve yields the result.

References 1. Laterza OF, Price CP, Scott MG. Cystatin C: An improved 4. O’Hare AM, Newman AB, Katz R et al. Cystatin C and estimator of glomerular filtration rate.Clin Chem. 2002; incident peripheral vascular disease in the elderly: results 48:699-707. from the Cardiovascular Health Study. Arch Intern Med. 2. Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C 2005; 165:2666-70. is superior to serum creatinine as a marker of kidney 5. Shlipak MG, Sarnak MJ, Katz R et al. Cystatin C and the function: a meta-analysis. Am J Kidney Dis. 2002; risk of death and cardiovascular events among elderly 40:221-6. persons. N Engl J Med. 2005; 352:2049-60. 3. Jenberg T, Lindahl B, James S et al. Cystatin C: A novel predictor of outcome in suspected or confirmed non-ST- elevation acute coronary syndrome. Circulation. 2004; 110:2342-8.

Test Overview Test Name Cystatin C <65 years: 0.50 -1.12 mg/L Reference Range >65 years: 0.55 – 1.21 mg/L Specimen Requirements 1 mL serum from SST. Centrifuge within one hour of collection. Notations Plasma from heparin tubes also acceptable Billing Code 83644 CPT Code 83520

Technical Information Contact: Scientific Information Contact:

Carolyn M. Bratush, MT(ASCP) Frederick Van Lente, PhD 216.444.2173 216.444.6252 [email protected] [email protected]