ReviewCystatin C as a marker of GFR—history, indications, and future research☆
Section snippets
What is cys-C and where is it produced?
Cystatin C (cys-C) is a low molecular mass protein that was initially known as inter alia γ-trace, post-γ-globulin, and gamma-CSF. The amino acid sequence of the single polypeptide chain of human cys-C was determined in 1981 [1]. The protein did not display any significant homology with the sequences of any protein at that time. Today, we know that the amino acid sequence of cys-C was the first sequence of the cystatin superfamily to be determined [2]. Two years later, cys-C was identified as
Cys-C in select patient groups
Select patient groups, whose muscle mass is either reduced or undergoes rapid changes, may benefit in particular from the development of a new marker of GFR. This is true for children and the elderly. Another target group includes patients for whom precise determination of GFR is critical, such as renal transplant recipients. It is therefore not surprising that many studies focus on these patient cohorts.
Diagnostic performance of cys-C
The independence from height, age, gender, and body composition as well as acute phase reactions, with renal function being the main determinant of cys-C serum concentration, makes cys-C an interesting candidate surrogate marker of GFR. Many studies tested for agreement of a cys-C-derived GFR and gold standard methods using Bland–Altman analysis [84]. Most studies found no systematic deviation but a scatter of ±40% (±2 standard deviations) between an exogenous clearance measurement and the GFR
Open questions and future work
Meta-analysis evidence was produced on the superiority of cys-C for the detection of impaired GFR in cross-sectional studies, even when using creatinine formulae based on height, age, gender, and so forth. Cys-C is therefore a useful screening tool to answer the question whether renal function is normal in a given subject. However, significantly more work is required to address the conflicting information about the higher intra-patient variability in longitudinal studies when compared to serum
Cost aspects
Regarding cost/practicability, both creatinine and cys-C (e.g., using the BN ProSpec® system platform) are both easily and rapidly determined. Currently, the Dade Behring N Latex cys-C assay is the only assay that has FDA approval. Creatinine is about $0.25 while cys-C is approximately $3.00 US. However, a 51Cr-EDTA or 99Tc-DTPA clearance study is in the $50.00 US range, and is technically difficult, results in radiation exposure, and requires a half-day hospitalization. The costs are based on
Conclusions
Cys-C is a fascinating novel marker of GFR that bears certain advantages over the most widely used surrogate marker of GFR: serum creatinine. There is high-level evidence that the diagnostic sensitivity for the detection of mildly impaired GFR is superior [16]. The independence from height, gender, age, and muscle mass is advantageous. Select patient groups such as children, the elderly, and patients with reduced muscle mass benefit in particular. The usefulness of cys-C as a marker of GFR in
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