We thank Kniepeiss et al. for their letter regarding the use of cystatin C versus serum creatinine and creatinine clearance as measures of renal function in orthotopic liver transplantation (OLT) and as predictors of post-OLT renal function. Evidence that cystatin C provides a more accurate estimation of glomerular filtration rate in pediatric and adult liver transplant recipients, compared with serum creatinine or creatinine-based formulas, is accumulating.1,2,3,4
In a study involving 90 patients undergoing OLT, Kniepeiss et al. showed that all of those with pre-OLT cystatin C values in the physiological range had stable post-OLT renal function, whereas patients with pre-OLT pathological cystatin C concentrations developed kidney dysfunction after transplantation. To determine the power of pre-OLT cystatin C level, creatinine clearance and serum creatinine concentration to predict the incidence of post-OLT renal failure, Kniepeiss et al. performed a stepwise binary logistic regression analysis. This analysis clearly showed that cystatin C concentration had prognostic significance (P < 0.05) at any timepoint, whereas serum creatinine level and creatinine clearance did not. The odds ratios for serum creatinine, creatinine clearance and cystatin C were 4.52, 1.07 and 60,011,090, respectively. The authors concluded that cystatin C “has high prognostic value for detection of early stage kidney dysfunction after liver transplantation” and suggested that “cystatin C could be another helpful marker for the screening and monitoring of patients before and after liver transplantation.”
Kniepeiss et al. provided important data that could eventually be clinically beneficial. We are concerned, however, that their conclusion might be too generalized. Kniepeiss et al. neglected to include their reference ranges for cystatin C (physiological and pathological), definition and etiology of kidney dysfunction, and duration of follow-up. Discrepancies between currently available studies of potential predictive factors for renal dysfunction following successful OLT might result, at least in part, from different definitions of renal dysfunction, etiologies of renal disease and duration of follow-up. Furthermore, rather than reporting the risk-factor profile for renal dysfunction pre-OLT and post OLT, Kniepeiss et al. loosely documented the risk-factor profile as “usual”. Documentation of a detailed risk-factor profile would have been invaluable in assessing the independent effect of cystatin C on renal function outcomes after OLT.
Nevertheless, the data of Kniepeiss et al. are in accordance with the findings of other investigators that cystatin C might be a better surrogate marker for glomerular filtration rate than serum creatinine or creatinine clearance, particularly in cirrhotic patients and recipients of liver grafts.1,2,3,4 We concur with Kniepeiss et al. that measurement of cystatin C level could be a useful tool for the screening and monitoring of patients prior to and after OLT. Several problems must be solved, however, before cystatin C can be recommended for routine use in clinical settings. These include the availability of standardized assays for cystatin C, the optimal cystatin C cutoff value for specific patient populations including cirrhotics, recipients of solid organ transplants, children and the elderly, and the relatively high cost of measuring cystatin C compared with that of determining serum creatinine level.
Hermida J et al. (2002) Relationship between serum cystatin C and creatinine in kidney and liver transplant patients. Clin Chimica Acta 316: 165–170
Samyn M et al. (2005) Cystatin C, an easy and reliable marker for assessment of renal dysfunction in children with liver disease and after liver transplantation. Liver Transpl 11: 344–349
Biancofiore G et al. (2006) Cystatin C as a marker of renal function immediately after liver transplantation. Liver Transpl 12: 285–291
Ling Q et al. (2007) Alternative definition of acute kidney injury following liver transplantation: based on serum creatinine and cystatin C levels. Transpl Proc 39: 3257–3260
The authors declare no competing financial interests.
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Pham, PT., Pham, PC. & Wilkinson, A. Authors' response to “Cystatin C has prognostic value after liver transplantation”. Nat Rev Nephrol 4, E2 (2008). https://doi.org/10.1038/ncpneph0766