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Abstract Diseases of the liver have been an important health issue since severe hepatitis diseases could lead to persistent inflammation, necrosis, and even liver cirrhosis and hepatoma. Hepatorenal syndrome is a reversible functional renal impairment that occurs in patients with chronic liver diseases. It is characterized by marked reduction in GFR with advanced liver cirrhosis or those with fulminant hepatic failure. So, close monitoring of chronic liver disease is recommended. In the last few decades, liver transplantation (LTx) has become a reliable life-saving procedure for patients with chronic end-stage liver diseases. Patients exposed to nephrotoxic drugs after liver transplantation need early detection of renal impairment if occurs and to modify immune-suppression. Cystatin C (Cys C, molecular weight [MW], 13 kDa) is freely filtered at that level of the glomerulus and virtually all is reabsorbed and metabolized by proximal tubular cells. An increasing serum Cys C level was found to be related to decreasing renal function. Thus, the present study was designed to evaluate the clinical application of cystatin C as a new marker for non-invasive estimation of glomerular filtration rate and as a reliable marker for early renal impairment in chronic liver diseases in children and to know if it is a more sensitive marker than creatinine, with comparison to radio-isotopic scan of kidney as a gold standard determination of GFR. The study groups were composed of: 58 children with chronic liver diseases, and 20 healthy children of matched age and sex as a control group. Diagnosis of chronic liver diseases based on clinical, biochemical, serological and histopathological investigations. All groups included in this study were subjected to thorough clinical examination, Laboratory investigations, measurement of serum Cys C concentration by particle induced immunonephlometry, imaging methods,Histopathological assessment and statistical analysis. 117 Cases of chronic liver diseases without renal impairment were 25 (group 1): including cholestasis 9 cases, Wilson disease 4 cases, infective hepatitis 3 cases, autoimmune hepatitis 3 cases, metabolic disease 2 cases, congenital hepatic fibrosis 2 cases, Budd Chiari syndrome one case and malignancy was one case. Cases of chronic liver diseases with renal impairment were 25 (group 2): including infective hepatitis 13 cases, Budd Chiari syndrome were 5 cases, congenital hepatic fibrosis were 4 cases and autoimmune hepatitis were 3 cases. Regarding disease duration there were statistical highly significant relation between chronic liver diseases with renal impairment. On other hand there was statistically insignificant relation between chronic liver diseases without renal impairment and after liver transplantation. According to the age, there was significant relation with cystatin C in chronic liver diseases with renal impairment, explained by increase the duration of the disease Regarding CBC results between studied groups there were statistical significant relation between control group & chronic liver diseases with and without renal impairment groups. Regarding to HB and platelets while there were highly statistical significant relation between chronic Liver diseases with renal impairment & control group regarding to RBCs, but there were no significant correlations between studied groups regarding to WBCs. Regarding liver function test (LFT) total, direct bilirubin, total protein, prothrombin concentration, albumin, AST and ALT there were statistically highly significant relation between control group & chronic liver diseases with and without renal impairment. There was statistically insignificant relation between control group & chronic liver diseases after liver transplantation. While in AST and ALT; there were statistically highly significant relation between control group & chronic liver diseases after liver transplantation. Regarding kidney function test (KFT) urea and creatinine, there were statistically highly significant relation between chronic liver diseases with renal impairment & control group, while in creatinine clearance; there were statistically highly significant relation between chronic liver diseases with renal impairment & control group (P<0.001), which showed affection of kidney function. Regarding Cystatin C there were highly significant relation in chronic liver diseases with renal impairment & control group. While there was statistically insignificant relation between chronic liver diseases without renal impairment and after transplantation& control group. Regarding Urea, creatinine and creatinine clearance (KFT); there was statistically significant relation with cystatin C in chronic liver diseases with renal impairment. In demonstration the validity of cystatin C in detecting cases of chronic liver disease with renal impairment the cut- off point detects renal impairment at 1.66 mg/dl with 100% sensitivity and 100% specificity, and the ROC curve is on longitudinal and vertical axis. There was no statistically significant relation between cystatin and abdominal sonographic finding among liver disease patients with and without renal impairment. The results of GFRs were determined from renogram, Cystatin C levels and creatinine clearance showed that cystatin C levels are closely correlated with 99Tc-DTPA renogram finding among liver disease patients with renal impairment. The correlation between renogram with cystatin c is considerably better than with creatinine clearance and Schwartz formula using a BlandAltman plot analysis. Conclusions: Serum creatinine is a crude marker of GFR and the most widely used measured of GFR. Serum creatinine typically varies slightly from day to day, age and gender associated differences in creatinine production are proportional to muscle mass and creatinine generation can vary significantly in a given individual over time when muscle mass changes. It does not increase until renal function decrease up to 50%. 119 Renogram, a radionuclide technique which using a complex of 99mTc-DTPA for quantification of GFR, is desired in association with renal imaging. This method is most useful in patients whom the urine collection is difficult, poorly cooperative patients, children and the ability to asses a single kidney GFR and do not require urine collection. This study has shown that a better correlation between renogram with Cystatin-C than with serum creatinine or creatinine clearance. Furthermore, Cystatin-C would be better alternative method in case having problems to obtain closest ideal methods for GFR determination in patients with mild and moderate stage of chronic kidney disease. So, Cystatin-C is a simple test that could be used for screening of normal, early, moderate, and severe renal dysfunction in children with chronic liver disease with or without renal impairment and after liver transplantation. |