Evaluation of serum cystatin C as a marker for detection of early renal function impairment in children with chronic liver disease

ABSTRACT

Evaluation of renal failure is essential in patients with decompensated liver cirrhosis, because a significant proportion of them manifest reduced glomerular filtration rate [GFR]. Careful assessment of GFR is critically important for prognosis because the indicators of renal function are sensitive markers of severity of liver dysfunction in cirrhosis and are better predictors of patient survival than estimating hepatic dysfunction. Plasma creatinine concentrations and calculated creatinine clearance are of limited values as GFR markers in patients with chronic liver diseases [CLD] especially liver cirrhosis. Recently, assessment of serum cystatin C concentrations was proposed as a possible indicator of early GFR changes in such patients. The aim of this work was to study the utility of measurement of serum cystatin C level as a marker of early detection of renal impairment in patients with CLD and to assess its correlation to the severity of liver dysfunction. This study was conducted on 30 children [17 males and 13 females] with CLD. Their ages ranged from 2 to 16 years. Twenty healthy children with matched age and sex were chosen as a control group. They were selected from those admitted to the Hepatology Unit of Pediatric Department, Tanta University Hospitals. In this study all patients were subjected to the following full clinical history, through physical examination, abdominal ultrasonography, histopathological assessment of liver biopsy and laboratory investigations. The latter included complete blood count, liver function tests, complete urine analysis, blood urea, serum creatinine, creatinine clearance [CrCI], hepatitis markers as well as measurement of serum cystatin concentrations by particle induced immunonephelometry. Control children were subjected to the whole previous investigations except liver biopsy. Severity of liver dysfunction in studied patients was classified into grades A, B and C according to modified Child-Pugh' classification. This study showed that mean CrCl values were significantly reduced in patients [77.03 +/- 17.4 ml/min/1.73m[2]] compared to controls [86.7 +/- 9.2 ml/min/1.73m[2]]. Mean CrCI values were impaired in 3 [10%] patients. All of them had ascites. Serum cystatin C levels were significantly higher in the studied patients [1.02 +/- 0.55mg/L] compared to controls [0.38 +/- 0.10mg/L], and significantly higher in grade C patients [1.35 +/- 0.65mg/L] than in those with grades B [0.92 +/- 0.46 mg/L] and A [0.73 +/- 0.29 mg/L]. Serum cystatin C levels were high in 10 [30%] patients of whom 70% [7/10] had ascites. Regarding ascitic patients, there was a significant reduction in CrCl values in ascitic compared to non-ascitic patients. Furthermore, there was a significant increase in serum cystatin C levels in ascitic compared to non-ascitic patients. Serum cystatin C correlated significantly with CrCI and severity of CLD as assessed by its correlation with liver function tests and Child's scores. ROC curve plots demonstrated that the area under the curve [AUC] of cystatin C [0.92] was greater than that of CrCI [0.76] and serum creatinine [0.58]. Therefore, sensitivity, specificity and diagnostic accuracy of cystatin C were higher than those of CrCl and both were better than those of serum creatinine. The positive and negative predictive values of serum cystatin C were higher than those of CrCl and serum creatinine. From this study, we can conclude that serum cystatin C is more accurate and simple than serum creatinine and creatinine clearance as a marker of GFR changes for prediction of early renal impairment in patients with CLD. Furthermore, serum cystatin C concentration was significantly high in patients with CLD that was correlated with the severity of liver dysfunction. Measurement of serum cystatin C may be recommended or at least added to serum creatinine in the routine assessment of early GFR changes in patients with CLD. However, further prospective comparative studies on a large scale with a gold standard method for measuring GFR are required to evaluate serum cystatin C concentration in different stages of renal impairment In children with CLD