Cystatin C – A Marker for Assessment of the Glomerular Filtration Rate in Patients with Cisplatin Chemotherapy

Abstract

Background: Cystatin C has recently been proposed as an ideal marker for glomerular filtration rate (GFR). In this study, cystatin C serum levels were evaluated in comparison to serum creatinine concentrations and inulin clearances in patients with normal kidney function receiving cisplatin-based chemotherapy to assess the validity of cystatin C as an alternative endogenous marker of GFR. Methods: Blood samples for the assessment of cystatin C, creatinine and inulin clearances were collected in patients before and after application of cisplatin in a clinical trial. Overall, 41 patients were included in the study, 35 of them were eligible receiving cisplatin in two different cisplatin-based chemotherapy schedules. Results: A 21% increase of cystatin C serum levels was demonstrated in the placebo group after application of cisplatin. Analysis of inulin clearances revealed a 23% loss of inulin clearance in patients of the placebo arm. In contrast, significant changes could not be detected by analysis of serum creatinine levels. Conclusions: Cystatin C represents a more sensitive clinical marker than serum creatinine for the early assessment of GFR damage caused by cisplatin. Changes in cystatin C serum concentrations correlate well to GFR decrease as measured by inulin clearance.

Cystatin C: current position and future prospects

“…These equations also appear to offer limited precision (52,110,113,116,124,129,130). As we shall see below, they could be more useful in certain subpopulations in which creatinine-based equations are particularly inaccurate, as in paediatrics (116,117,124), transplantation (113,115,(131)(132)(133) or oncology (134). Validation studies on large independent populations, however, would appear to be needed.…”

“…In addition, as this study included renal failure patients (inulin clearance between 43.6 and 115.1 mL/min) it is impossible to compare the serum cystatin concentrations found with reference values in the literature (134).…”

“…Several studies have examined the use of serum CysC in assessing nephrotoxicity from drugs used to treat cancer, particularly cisplatin (134,254,255,259). Most of these have been performed in children, in whom measurement of urinary creatinine clearance is particularly difficult and all agree that serum cystatin is a far more sensitive marker than serum creatinine to detect reduced GFR or creatinine clearance after cisplatin administration.…”

“…Most of these have been performed in children, in whom measurement of urinary creatinine clearance is particularly difficult and all agree that serum cystatin is a far more sensitive marker than serum creatinine to detect reduced GFR or creatinine clearance after cisplatin administration. The most convincing is the Benohr study which showed a 21% increase in serum cystatin on day 5 of cisplatin administration in parallel with a 23% fall in inulin clearance (134). Serum cystatin also appears to be an effective tool to predict a clinically significant fall in urinary creatinine clearance (254,255).…”

Evaluation of the Renal Function Using Cystatin C Level in the Patients Receiving Cisplatin-Based Chemotherapy

“…6 In recent years, data have shown that cystatin C, a cysteine protein kinase inhibitor, determines GFR more accurately. [7][8][9] Cystatin C is constituted of 120 amino acids and belongs to the cystatin superfamily. It is found in a constant concentration in all cells with nucleus and is excreted to the blood stream.…”