Determination of the production rate and non‐renal clearance of cystatin C and estimation of the glomerular filtration rate from the serum concentration of cystatin C in humans

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Abstract
Cystatin C has been proposed as an endogenous marker for measuring glomerular filtration rate (GFR) and is regarded as being equivalent to or better than creatinine. However, there are no published data on the production rate (Cyspr) or on the non‐renal clearance of cystatin C (CLnr) in humans, which are essential parameters for GFR calculation. GFR was determined by measuring the plasma clearance of iohexol. Cystatin C, creatinine, urea and albumin were determined on the same serum samples as iohexol; 381 patients with a GFR range of 12–151 ml/min/1.73 m2, and 70 patients on haemodialysis were evaluated. Renal clearance of cystatin C (CLr) equals GFR * S (the sieving coefficient). Plasma clearance (CL) = CLr+CLnr. The relationship between Cyspr and the elimination rate (CL * serum‐cystatin C) can be expressed as Cyspr = (S * GFR+CLnr) * serum‐cystatin C. Assuming that the unknown values of Cyspr and CLnr are independent of GFR, the equation can be solved from GFR (iohexol clearance) and serum cystatin C (s‐Cys) patient data. For S = 1, we found Cyspr = 0.124±0.023 mg/min/1.73 m2 and Clnr = 22.3 ml/min/1.73 m2. For S = 0.94, found in rats, the values will be Cyspr = 0.117 mg/min/1.73 m2 and Clnr = 21 ml/min/1.73 m2 and S‐Cys in 70 patients on chronic haemodialysis was found to be 5.74±1.15 mg/l, in agreement with a calculated value of 5.56 mg/l (s‐Cys = 124/22.3) for GFR = zero. The mean value of the calculated Clnr for the 70 patients was 22.7±6.6 ml/min/1.73 m2, which confirms the calculated level and indicates its biological variation. We thus propose the following formula for calculating GFR using the values found for CLnr and Cyspr in this study: GFR = 124/s‐Cys−22.3 ml/min/1.73 m2, where serum cystatin C concentration is given as mg/l.