Cystatin C: an improved estimator of glomerular filtration rate?
BACKGROUND
Glomerular filtration rate (GFR) is routinely assessed by measuring the concentrations of endogenous serum markers such as blood urea nitrogen and serum creatinine (SCr). Although widely used, these endogenous markers are not ideal and do not perform optimally in certain clinical settings. The purpose of this review is to critically review the potential utility of cystatin C (CysC), especially in patient populations in which CysC may have an advantage over routinely used endogenous markers of GFR.


METHODS
In a narrative approach, we extensively review publications, primarily from the last 5 years, that address the development of methods to measure CysC, reference intervals, and the diagnostic accuracy of CysC to assess GFR. Between June 2000 and September 2001 Medline was searched using "cystatin c" as a textword, and articles that examined >75 individuals (except for renal transplant studies) and/or used accepted "gold standards" for assessing GFR were selected for inclusion. A total of 17 studies are reviewed that provide reference interval data for several populations. A total of 24 studies make conclusions about the utility of CysC vs SCr and/or creatinine clearance, with 20 providing data on the sensitivity and specificity of CysC for detecting impaired GFR. These publications are organized into subgroups that deal with specific patient populations or clinical situations.


BACKGROUND
This review focuses on two areas: (a) the evolution of immunoassays used to determine the concentration of CysC in serum, their analytic sensitivity, and reference intervals; and (b) the diagnostic performance of CysC against other renal markers in the general population and in specific subpopulations of patients.


CONCLUSIONS
Studies of reference intervals for CysC overwhelmingly demonstrated that CysC values in blood are independent of age and sex. Of the 24 studies that examined clinical utility, 15 concluded that CysC is superior to SCr, whereas 9 concluded that CysC is equivalent but provides no advantage. Summary ROC plot analysis of 20 studies that provide sensitivity and specificity data strongly suggests that CysC will be superior to SCr for detecting impaired GFR. Taken together, it is clear that CysC performs at least as well as SCr in the population at large and that it is likely to be superior to SCr in specific patient populations.
Laterza
Omar F
OF
Washington University School of Medicine, Department of Pathology and Immunology, Division of Laboratory Medicine, Box 8118, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
Price
Christopher P
CP
Scott
Mitchell G
MG
D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000032:analysis; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D064420:Drug-Related Side Effects and Adverse Reactions; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D016030:Kidney Transplantation; D012372:ROC Curve; D012016:Reference Values
D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D003404:Creatinine