Elsevier

Clinical Biochemistry

Volume 37, Issue 2, February 2004, Pages 94-97
Clinical Biochemistry

Relationship between plasma Cystatin C and creatinine in chronic renal diseases and Tx-transplant patients

https://doi.org/10.1016/j.clinbiochem.2003.10.009Get rights and content

Abstract

Objectives: Glomerular filtration rate (GFR) is the best overall index of renal function in health and disease. Recently, Cystatin C (Cyst C), a low molecular weight protein freely filtered through the glomerulus, and almost completely reabsorbed and catabolized by tubular cells, has been proposed as a new and very sensitive serum marker of change in GFR. This study investigated the relationship between Cyst C and creatinine (CR) in renal disease patients.

Methods: Serum Cyst C was determined by particle-enhanced immunoturbidimetry using the Cyst C PET-kit. The results could be obtained within 1 h. Cuvettes were washed before the Cyst C assay as recommended. Serum CR, BUN and albumin were determined by auto-analyzer.

Results: A strong correlation was observed between Cyst C and CR (P = 0.001, r = 0.764 and P = 0.0001, r = 0.888, respectively) in prehemodialysis (pre-HD) and kidney transplantation (Tx-kidney), whereas there was a weak correlation in continuous ambulatory peritoneal dialysis (CAPD) (P = 0.05, r = 0.535).

Conclusion: These findings suggest that serum Cyst C may be considered as a sensitive predictive parameter for reduced GFR. It is of value for the laboratory diagnosis of chronic renal failure and should be preferentially used for CR clearance.

Introduction

Glomerular filtration rate (GFR) is defined as the clearance of a substance carried in the plasma that is not metabolized outside the kidney and that is filtered freely through the glomerular membrane, and GFR is the main indicator of kidney function [1], [2]. Serum creatinine (CR) and creatinine clearance (CRC) are widely used as measures of GFR [3], but serum CR is not an accurate marker of GFR. Alteration in renal handling and metabolism of CR and methodological interferences may affect the levels of serum CR [3], [4]. Tubular cells secrete a small but important part of CR, which leads to overestimation of GFR, especially at the lower end of the filtration rate [1], [2]. In addition, serum CR is influenced by sex, muscle mass and age [1].

Cystatin C (Cyst C) has recently been shown to be an accurate marker GFR with advantages over serum CR [2], [3], [4], [5], [6]. Cyst C is a potent inhibitor of cysteine proteases and it is found in extracellular fluids. It is a low molecular weight protein (13.359 kDa), with a stable production rate by all nucleated cells, and is freely filtered through the glomeruli and almost completely reabsorbed and catabolized by proximal tubular cells. Inflammation and malignancy have no effect on its serum concentration [7]. Clearance of Cyst C cannot be measured because it is broken down in the cells of the proximal tubule, whereas its serum concentration is a good marker of GFR [1], [2], [3], [4], [5]. Recent studies have shown that serum Cyst C can be used as an accurate marker of GFR in adults and children [1], [4], [8].

In this study, we investigated the relationship between serum Cyst C and CR in prehemodialysis (pre-HD), hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), kidney transplantation (Tx-kidney) and healthy control subjects.

Section snippets

Patients and controls

We investigated 59 patients: 29 female and 30 male chronic renal failure (CRF) recipients, age 41.3 ± 13.0 years; 10 female and 5 male HD recipients, age 43.1 ± 13.4 years; 7 female and 7 male CAPD patients, age 37.4 ± 11.6 years; 7 female and 8 male (pre-HD) patients, age 50.2 ± 12.7 years; 5 female and 10 male Tx-kidney recipients at 1–12 months after transplantation, age 30.1 ± 6.3 years; and 20 healthy controls, 10 female and 10 male age 41.0 ± 5.7 years. Exclusion criteria were patients

Results

The clinical characteristics of the patient groups are shown in Table 1. Serum BUN level was significantly increased, whereas albumin level was significantly decreased in all groups when compared to control group and to each other (P = 0.0001). According to the Kruskal–Wallis test, glucose level was significantly decreased in all groups (as median, P = 0.0001) (Table 1). Serum CR levels were found significantly increased in pre-HD, HD, CAPD and Tx-kidney patients when compared to control group (

Discussion

Several studies have suggested that Cyst C might be a better potential marker of GFR than plasma CR [5], [6], [10], [11], [12], [13] in HD, CAPD and Tx-kidney [14], [15]. It is known that Cyst C is a low molecular weight protein with a stable production rate by all nucleated cells. Moreover, it can freely filter through the glomerulus and can be almost completely reabsorbed and catabolized by proximal tubular cells. The production rate of Cyst C is less altered by non-renal factors than the

Acknowledgements

The authors thank Ziya Karahan for providing Cyst C kits and Diagno Corp. for the automated measurement of Cyst C.

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