Glomerular filtration rate assessment in individuals after orthotopic liver transplantation based on serum cystatin C levels

Abstract

Individuals after orthotopic liver transplantation (OLT) often show renal dysfunction, which may substantially affect the post-OLT course. Renal function after OLT is commonly assessed by means of serum creatinine (S,,) concentration or renal creatinine clearance (C,,). A glomerular filtration rate (GFR) estimate based on S,, level is not accurate enough because even a more marked decrease in GFR need not be associated with an increase in S,, level, especially in jaundiced patients. The study intends to try to estimate GFR in individuals after OLT by means of determining serum cystatin C (Sv,) concentrations. In 58 individuals (mean age, 49 k 7 years; 31 men, 27 women) at various intervals from OLT (mean, 14 f 10 months), GFR was estimated by using simultaneous determinations of !Scyst, S,, C,,, and renal inulin clearance (Cin). In most subjects (91.3%), Cin was decreased to less than the lower limit of normal (80 mL/min/1.73 m'). A significant correlation (r = 0.70; P < .001) was found between l/Sqst and Cin. Receiver operating characteristic analysis was performed on S and S,, using a Cin cutoff value of 80 mWmid1.73 m . The area under the curve for S, , was 0.912 A 0.044, and that for S,, 0.899 f 0.049. There was no statistically significant difference between these values. The sensitivity for a S, , level of 1.20 mg/L (upper limit of normal value) to detect a decrease in GFR (measured as Cin) below the lower limit of normal (80 mWmid1.73 m') was 96.1%. The sensitivity of S, , level was significantly greater (P < .01) than the sensitivity of S,, level for men and at borderline significance for women (P = .05).Findings support the assumption that a S, , level less than 1.2 mg/L indicates with a high degree of probability (P C .001) that GFR is not decreased to less than the normal limit. S, , assessment in individuals after OLT could be proposed as a confirmatory test of a decrease in GFR in individuals with normal S,, levels. (Liver Transpl2002;8: T'574-577.)

A tale of two markers

“…Surprisingly, Scr had shown good correlation with GFR, especially in the female OLT patients, but is the result from the study by Schück et al 10 enough? Cystatin C, on the other hand, has performed well in other clinical situations and is at least equivalent to Scr in the study by Schück et al 10 It also has the advantage in the jaundice patients because its assay is not altered by bilirubin. 17 Finally, in the study by Schück et al, 10 there were four female patients with GFR Ͻ15 mL/min/1.73m 2 , all of whom had Scr levels below 200 mol/L (2.3 mg/dL).…”

“…Depending on the method used and the levels of bilirubin, serum creatinine levels could have been falsely reduced. 26 To be fair to cystatin C, it also encountered disadvantages in the study by Schück et al 10 First, many factors that hindered Scr in the pretransplant state were no longer present in the posttransplant patients. Many reports, including the one by Schück et al, 10 made the assumption that Scr is a poor marker based mainly on pretransplant data.…”

“…26 To be fair to cystatin C, it also encountered disadvantages in the study by Schück et al 10 First, many factors that hindered Scr in the pretransplant state were no longer present in the posttransplant patients. Many reports, including the one by Schück et al, 10 made the assumption that Scr is a poor marker based mainly on pretransplant data. To the best of my knowledge, this was the first study that compared Scr with GFR after liver transplantation, and to the surprise of the investigators, Scr performed quite well.…”

“…One would think that with all of the advantages of cystatin C, it would have performed better than Scr in the study by Schück et al 10 First, the investigators included pediatric patients (youngest, age 10 years) in the analysis. Pediatric patients have lower normal limits of creatinine, which are based on their age, and should be analyzed separately.…”

“…[17][18][19][20][21][22] Currently, two automated assays are available that make determination of serum cystatin C level as easy and convenient as determining Scr. 23,24 In the article by Schück et al, 10 the ability of cystatin C to predict GFR in the posttransplant population was tested. Schück et al 10 evaluated serum cystatin C in 58 liver allograft recipients who underwent transplantation between 1995 and 1999.…”