A Systematic Review And Meta-analysis Of Cystatin C In The Diagnosis Of Acute Kidney Injury And Hepatorenal Syndrome In Patients With Liver Cirrhosis

Background:Liver cirrhosis is a chronic progressive liver disease induced by one or more causes.The pathological features of cirrhosis are regenerative nodules and pseudolobular formation.Complications of liver cirrhosis are difficult to control,acute kidney injury is one of the serious complications.The latest consensus of the International Ascites Club recommends that the diagnostic criteria for acute kidney injury in patiens with cirrhosis include:serum creatinine level increased by?26.5?mol/L(0.3mg/dL)within 48h,or within 7 days compared to baseline(The creatinine value obtained during the 3 month or the most recent creatinine value before admission)increased by?50%.Hepatorenal syndrome is a special type of acute kidney injury.The clinical manifestations are elevated serum creatinine,decreased glomerular filtration rate,and oliguria or anuria.Hepatorenal syndrome is classified into type I hepatorenal syndrome and type II hepatorenal syndrome.The 30 day mortality rate of acute kidney injury in cirrhosis is 10 times of that of hospitalized patiens without acute kidney injury.Acute kidney injury in cirrhosis is an independent risk factor for increased mortality.Therefore,early diagnosis and treatment of renal dysfunction in patients with cirrhosis are important to improve the survival rate of cirrhosis patients with kidney injury.Serum cystatin C has been indicated to be a relatively accurate marker to evaluate renal function in many diseases.However,there has been no consistent conclusion regarding the correlation and diagnostic accuracy of serum cystatin C in the renal dysfunction of cirrhosis patients.Aim:This meta-analysis was conducted to investigate the relationship between serum cystatin C and acute kidney injury or hepatorenal syndrome and the the diagnostic value of serum cystatin C for acute kidney injury or hepatorenal syndrome in patients with cirrhosis.Method:The PubMed,Embase and CNKI database were systematically and comprehensively searched to collect all relevant studies of acute kidney injury and hepatorenal syndrome in patients with cirrhosis.The search time was from creation of database to November 2018,and the relevant references were manually searched.Inclusion criteria were developed based on relevant strategies.The literature was included according to the inclusion criteria,and the quality of the final included literature was evaluated.Two investigators searched the literature and screened the documents obtained by the search,collected the data included in the study and extracted relevant data,and finally evaluated the quality of the included documents.Meta-analysis was performed on the data extracted from the study using Sata 13.0 software.Heterogeneity was quantified by Q test and I~2 test.When heterogeneity was high(P?0.1,I~2>50%),the random effects model was used,and the heterogeneity source was explored through subgroup analysis;when heterogeneity was low(P>0.1,I~2?50%),a fixed-effects model was used.(SMD)and 95%CI were used to evaluate the associations of serum cystatin C with renal dysfunction of cirrhosis including acute kidney injury and hepatorenal syndrome.The pooled sensitivity,specificity and the area under the receiver operating characteristic curve were used to evaluate the accuracy of serum cystatin C in the diagnosis of acute kidney injury and hepatorenal syndrome.Results:A total of 27 related studies,including 2,861 patients with cirrhosis,were included in this study.(1).Serum cystatin C and acute kidney injury of cirrhosis:A total of 10 eligible studies reported serum cystatin C in cirrhosis with acute kidney injury.Nine of the 10 studies reported a relationship between serum cystatin C and acute kidney injury and 1274 patients with cirrhosis,including 424 patients with acute cirrhosis and 750patients without acute kidney injury were included.Serum cystatin C levels in patients with cirrhosis and acute kidney injury were significantly higher than those in patients without acute kidney injury(SMD=2.15,95%CI 1.36-2.95,P<0.001).Six of the 10 studies eligible studies reported the diagnostic value of serum cystatin Cfor acute kidney injury in patients with cirrhosis.A total of 650 patients with cirrhosis,including264 patients with acute kidney injury and 386 patients without acute kidney injury were included.The pooled sensitivity,specificity and area under the receiver operating characteristic curve of serum cystatin C for acute kidney injury were 0.86,0.81 and 0.90,respectively.(2).Serum cystatin C and hepatorenal syndrome of cirrhosis:A total of 17 eligible studies reported cystatin C in cirrhosis with hepatorenal syndrome.Among the 17 eligible studies,15 studies reported serum cystatin C levels in liver cirrhosis with hepatorenal syndrome.A total of 1020 patients with cirrhosis,including 371cases of cirrhosis with hepatorenal syndrome,and 1831 cases of cirrhosis with hepatorenal syndrome were included.Serum cystatin C levels in patients with hepatorenal syndrome were significantly higher than those without hepatorenal syndrome(SMD=2.09,95%CI1.44-2.74,P<0.001).Two studies reported the relationship between serum cystatin C and type I hepatorenal syndrome and type II hepatorenal syndrome,including 46 cases of type I hepatorenal syndrome and 48 cases of type II hepatorenal syndrome and 189 cases without hepatorenal syndrome,the serum cystatin C levels of pooled analysis in type I hepatorenal syndrome(SMD=2.92,95%CI 2.22-3.63,P<0.001)or type II hepatorenal syndrome(SMD=1.71,95%CI 0.62-2.80,P<0.001)were higher than those of patients without hepatorenal syndrome.There are 6 eligible studies reported the diagnostic value of serum cystatin C in the diagnosis of hepatorenal syndrome in patients with cirrhosis,including 131 cases with hepatorenal syndrome and 259 cases without hepatorenal syndrome.The pooled sensitivity,specificity,and area under the receiver operating characteristic curve for hepatorenal syndrome of cirrhosis were 0.80,0.78 and 0.85,respectively.Conclusion:Serum cystatin C levels in cirrhotic patients with acute kidney injury or hepatorenal syndrome are significantly elevated compared with in those without acute kidney injury or hepatorenal syndrome.Moreover,serum cystatin C is a reliable and effective indicator for the diagnosis of acute kidney injury or hepatorenal syndrome in patients with cirrhosis.