Cystatin C as a marker of renal function immediately after liver transplantation

Abstract

To verify whether cystatin C may be of some use as a renal function marker immediately after orthotopic liver transplantation (OLT), we compared serum cystatin C (S Cyst ), serum creatinine (S cr ), and creatinine clearance (C cr ) levels with the glomerular filtration rate (GFR). On postoperative days 1, 3, 5, and 7, S Cyst and S cr was measured in simultaneously drawn blood samples, whereas C cr was calculated using a complete 24-hour urine collection. The GFR was determined on the same days by means of iohexol plasma clearance (I-GFR). The correlation between 1/S Cyst and I-GFR was stronger than that of 1/S cr or C cr (P < 0.01). In the case of moderate reductions in I-GFR (80-60 mL/minute/1.73 m 2 ), S cr remained within the normal range, whereas the increase in S cyst was beyond its upper limit; for I-GFR reductions to lower levels (59-40 mL/minute/1.73 m 2 ), S cr increased slightly, whereas S cyst was twice its upper normal limit. When we isolated all of the I-GFR values on days 3, 5, and 7 that were >30% lower than that recorded on the first postoperative day, S Cyst (P < 0.0001) and S cr (P < 0.01) levels were increased, whereas C cr remained unchanged (P ‫؍‬ 0.09). Receiver operating characteristic (ROC) area-under-the-curve analysis showed that the diagnostic accuracy of S cyst was better than that of S cr and C cr . S cyst levels of 1.4, 1.7, and 2.2 mg/L respectively predicted I-GFR levels of 80, 60, and 40 mL/minute/1.73 m 2 . In conclusion, cystatin C is a reliable marker of renal function during the immediate post-OLT period, especially when the goal is to identify moderate changes in GFR. It has been widely demonstrated that acute renal failure can severely affect the postoperative course of a complex procedure such as orthotopic liver transplantation (OLT). 1,2 As renal function can be threatened for different reasons in the period immediately following OLT (i.e., hemodynamic disturbances, drug nephrotoxicity, acute surgical or infectious complications), it is very important for clinicians to have access to sensitive and reliable markers that can promptly identify renal dysfunction from its initial stage in order to allow them to adopt the necessary preventive and supportive measures for avoiding or containing the development of renal damage.Although commonly used, the measurement of serum creatinine (S cr ) and the calculation of creatinine clearance (C cr ) are not very reliable in cirrhotic patients undergoing OLT because some of the peculiarities of the liver disease (reduced muscle mass, decreased creatinine biosynthesis, high blood bilirubin levels) can lead to false results. [3][4][5] Furthermore, it has been reported that making routine S cr measurements is an insensitive way of assessing renal function in patients adminis-

Cystatin C: current position and future prospects

“…The Hoek et al (119) and Larsson et al (120) equations perform at least as well as the MDRD equation in these populations (131). CysC appears to be a better predictor of acute renal failure after liver transplantation (204), including children (146), and to provide better follow-up for moderate changes in renal function (152).…”

“…In this context, several groups have tried to establish whether CysC could be a more sensitive marker than creatinine for the early detection of deterioration in GFR in renal transplant patients. Results are inconsistent, some authors finding CysC to offer improved sensitivity (90,91,122,152), whereas according to others the diagnostic performance (assessed by ROC curve methods) does not differ significantly between the two markers, in particular for the critical GFR threshold of 60 mL/min (52, 92, 153). …”

How to estimate GFR-serum creatinine, serum cystatin C or equations?

“…Of note, serum cystatin C concentration increases already with mildly reduced GFR of 70 to 90 mL/min [39,[47][48][49], i.e., in the "creatinine-blind range". Furthermore, recent longitudinal studies have shown that cystatin C concentrations rise earlier in acute kidney injury on intensive care unit, after liver transplantation, cardiac surgery, cisplatin chemotherapy and coronary angiography [51][52][53][54][55][56], following uninephrectomy [57], and in progressive diabetic nephropathy [32]. First studies have demonstrated that serum β-trace protein may be as valuable as cystatin C to detect mildly reduced GFR [58][59][60].…”

Hepatorenal syndrome: the 8th international consensus conference of the Acute Dialysis Quality Initiative (ADQI) Group

“…Furthermore, the measurement of S Cr using the Jaffe method can be artificially lowered due to hyperbilirubinemia [13], or raised by cephalosporins [14] leading to variability in MELD scores [15]. Serum cystatin C has been suggested as a sensitive marker of renal function [16-22]; however, recent studies have shown that like S Cr , cystatin C is affected by age, gender, muscle mass and liver disease and overestimates renal function in patients with cirrhosis [17,23]. …”