NDT Advance Access originally published online on November 4, 2007
Nephrology Dialysis Transplantation 2008 23(3):1072-1073; doi:10.1093/ndt/gfm771
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Plasma cystatin C for estimating residual GFR (rGFR) in dialysis patients
E-mail: martin.tidman{at}orebroll.seSir,
Hoek et al. present a new formula for the estimation of residual GFR (rGFR) in dialysis patients using the plasma (P) cystatin C level [1].
The formula is constructed by regression from a group of haemodialysis (HD) and peritoneal dialysis (PD) patients with a very narrow GFR interval,
1–6.5 ml/min. The slope factor of the formula is very low, resulting in poor discrimination, i.e. P-cystatin C values of 4 and 7.6 mg/l (CI limits of the HD validation group) give rGFR of 4.4 and 2.0 ml/min/1.73 m2 respectively. The superior bias, accuracy and precision of the formula compared to the MDRD formula can be explained by the patient inclusion criteria and the narrow result interval of the formula. In addition, we would like to ask what cystatin C concentration do anuric dialysis patients have? Putting rGFR = 0 in the formula described gives a P-cystatin C concentration of 31.4 mg/l, which is a very high and very unlikely value considering the confidence interval of the study group. Figure 1 compares three different formulae for eGFR.
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The authors hypothesis for the low-slope factor of their formula is a greatly decreased production rate of cystatin C in dialysis patients,
25% of that of patients with mild renal insufficiency (from 0.08 to 0.02 mg/min) according to their own previous study [2]. The production rate of cystatin C has been shown to be constant in other situations and we have found that all CKD stages fit into our formula (100/ S-cysC – 14 using Gentian's turbidimetric method) [3] as well as anuric dialysis patients (Tidman et al., unpublished data). The authors support for the hypothesis of reduced production rate is that the new steady-state concentration of P-cystatin C is reached much earlier than that for creatinine after acute renal failure. Our explanation is that cystatin C has a lower distribution volume (1/3) and a higher extra-renal clearance than creatinine [4]. It may take 2 weeks to reach a new steady state for creatinine, when GFR is <5 ml/min [5]. Thus, the MDRD formula cannot be used to calculate rGFR in HD patients, as it implies a steady-state concentration of creatinine and will give rise to falsely high eGFR values until this steady state is reached. Cystatin C would be more suitable in this respect, but we think that the biological variation in the production rate and extra-renal clearance is too high to make its use for measuring rGFR acceptable. An error of say 4 ml/min in GFR is insignificant at normal renal function but makes the result meaningless in a dialysis patient. We use plasma clearance of iohexol to measure rGFR in our HD patients [6]. Conflict of interest statement. None declared.
1 Department of Medicine, University Hospital of Örebro S-701 85 Örebro, Sweden 2 Department of Clinical Chemistry University Hospital of Örebro S-701 85 Örebro, Sweden
References
- Hoek FJ, Korevaar JC, Dekker FW, et al. Estimation of residual glomerular filtration rate in dialysis patients from the plasma cystatin C level. Nephrol Dial Transplant (2007) 22:1633–1638.
[Abstract/Free Full Text] - Hoek FJ, Kemperman FA, Krediet RT. A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular filtration rate. Nephrol Dial Transplant (2003) 18:2024–2031.
[Abstract/Free Full Text] - Tidman M, Sjöström P, Jones I. New formulae for estimating glomerular filtration rate based upon S-creatinine and S-cystatin C and a combination of the two. A comparison of GFR estimating formulae. Nephrol Dial Transplant (2007) (accepted).
- Sjöström P, Tidman M, Jones I. The shorter T1/2 of cystatin C explains the earlier change of its serum level compared to serum creatinine. Clin Nephrol (2004) 62:241–242.[Web of Science][Medline]
- Sjostrom P, Tidman M, Jones I. Cystatin C is an earlier marker of changes in renal function than creatinine. ASN, Poster Renal Week, San Diego, 2006.
- Sterner G, Frennby B, Månsson S, et al. Assessing residual renal function and efficiency of hemodialysis—an application for urographic contrast media. Nephron (2000) 85:324–333.[CrossRef][Web of Science][Medline]
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), Hoek's formula for mild renal impairment (80.35/ S-Cys – 4.32;
) and for HD patients (21/S-Cys – 0.77;
).