Elsevier

Clinica Chimica Acta

Volume 323, Issues 1–2, September 2002, Pages 121-128
Clinica Chimica Acta

Measurement of cystatin-C and creatinine in urine

https://doi.org/10.1016/S0009-8981(02)00177-8Get rights and content

Abstract

Background: The concentration of serum cystatin-C (Cys-C) is highly correlated with creatinine (Cr), and is mainly determined by glomerular filtration; thus, Cys-C may be an index of the glomerular filtration rate (GFR). However, the kinetics of urinary Cys-C and Cr excretions are unclear. Thus, we investigated the kinetics of urinary Cys-C and Cr excretions, and examined whether the urinary Cys-C concentration can be used as a marker of renal function. Methods: The urinary excretion of Cys-C and Cr was evaluated in 1670 healthy subjects and 217 patients with proteinuria. We also investigated the urinary Cys-C concentration in 52 patients with chronic renal failure. Results: There was a good correlation between the urinary concentrations of Cys-C and Cr in the healthy group. This relation was also observed in patients showing persistent proteinuria without tubular cell damage. The mean urinary Cr concentration increased with age, and it was affected by the muscle mass. In contrast, the urinary Cys-C concentration was not affected by the muscle mass, and the concentration remained constant for all ages. We further found that the ratio of Cys-C to Cr (CCR) is a good index of the state of Cys-C reabsorption in the proximal tubules. Conclusions: The urinary CCR can be a marker of renal tubular dysfunction. In addition, when CCR was in the normal range, the urinary Cys-C concentration accurately reflected the glomerular filtration function.

Introduction

Cystatin-C (Cys-C) is a low molecular weight (Mr 13,359) [1] cysteine proteinase inhibitor with a pI of 9.3 [2]. The gene for Cys-C (7.3 kDa) has been sequenced and localized to chromosome 20 [3]. The structure of the gene appears to be of the housekeeping type, which is compatible with a stable production rate by most nucleated cells [4], and as such, it meets one of the criteria to be considered as an endogenous marker of the glomerular filtration rate (GFR) [5].

Due to its low molecular weight, and in combination with its positive charge, Cys-C is freely filtered by the renal glomeruli, further advancing its use as a marker of GFR [6]. Several studies have reported the use of serum Cys-C as an indirect measure of GFR, demonstrating superior diagnostic performance compared with serum creatinine and in some instances the creatinine clearance [7], [8], [9], [10], [11].

The urinary concentration of Cys-C is low, and its concentration in normal subjects is about 100 μg/l. It was shown that the concentration of Cys-C in urine from patients with renal tubular disorders is raised approximately 200-fold [12]. Popovic et al. [13] isolated two isoelectric forms of Cys-C with pI 9.2 and 7.8 from the urine of patients with different nephrological disorders.

However, the details of the kinetics of urinary excretion remain to be elucidated. The objective of this study was to investigate the kinetics of urinary Cys-C and Cr excretions in detail and to investigate whether the urinary Cys-C concentration can be a marker of renal function.

Section snippets

Subjects

We analyzed random urine samples obtained from 1120 healthy subjects (40 males and 40 females of each age from 5 to 18 years) to study the kinetics of urinary Cys-C and Cr excretions. We also examined random urine samples from 550 healthy adults (265 males and 285 females aged 20–71 years). To evaluate the usefulness of urinary Cys-C as a marker protein of renal function, we tested random samples from 217 patients (103 males and 114 females aged 10–69 years) with proteinuria (>300 mg/l). We

Standard curve and sensitivity

As shown in Fig. 1, the calibration was prepared using human recombinant Cys-C as a standard substance. The measurement sensitivity was approximately 5 μg/l. The measurement range was 5–700 μg/l.

Imprecision and recovery

Table 1 shows the intraassay and interassay imprecision of Cys-C using two urine specimens. The recovery of urine (n=5) with the addition of 100 μg/l Cys-C was between 94% and 102%.

Stability of Cys-C in urine

A high concentration of Cys-C urine was added to five urine specimens from healthy adults with pH values ranging from 5.0

Discussion

Simonsen et al. [16] initially reported in 1985 that serum Cys-C can be used as a marker for GFR. They correlated the reciprocal values of the protein to 51Cr-EDTA-Clearance in a group of patients with different kidney diseases, with various degrees of impairment of renal function, and found serum Cys-C concentrations to be as closely correlated to GFR as serum levels of creatinine. Subsequently, several studies have suggested that serum Cys-C is a better marker for GFR than serum creatinine [7]

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