Cystatin C: An Improved Estimator of Glomerular Filtration Rate?

Abstract

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. Approach: 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. Content: 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. Summary: 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.

Cystatins in Immune System

“…128,129 Studies on the sensitivity and specificity of cystatin C for detecting impaired GFR strongly suggest it to be superior diagnostic marker to creatinine for detecting impaired GFR. 130 However, caution is necessary in case of patients with malignancy or other diseases with increased activity of cyteine proteases which exhibit increased cystatin C levels irrelevant to kidney function. 131 It has been suggested that disturbance of the cystatin E/M-cathepsin pathway could contribute to dysregulated skin barrier function as observed in the inflammatory dermatoses.…”

Novel approaches to assessing renal function in cirrhotic liver disease

“…A recent review of 24 studies comparing cystatin C to serum creatinine reported that cystatin C outperformed serum creatinine in 15 studies and was at least as good in the remainder. 5 The majority of these studies examined patients with intrinsic renal disease (including pre-and post-renal transplant patients) or healthy disease-free controls. The area under the curve (AUC) constructed from receiver operator characteristic curves for all studies showed that cystatin C was a better marker of renal function than serum creatinine when compared against clearance of exogenous substances (AUC 0.95 cystatin C vs. 0.91 serum creatinine).…”

Cystatin C and NT‐proBNP, a powerful combination of biomarkers for predicting cardiovascular mortality in elderly patients with heart failure: results from a 10‐year study in primary care

“…8 -11 Therefore, cystatin C is deemed a useful biomarker of renal function. 9,12,13 Recent reports have indicated that cystatin C might also be a prognostic indicator of cardiovascular (CV) mortality. Lassus et al 14…”