Diagnostic Accuracy Of Serum Cystatin C For Acute Kidney Injury In Adults: A Meta-analysis

[Background]Acute kidney injury(AKI)is a commonly serious complication in hospitalized patients,associated with high morbidity and mortality.The value of serum cystatin C(SCys-C)for diagnosing AKI has not been fully discussed.This meta-analysis was aimed to investigate the overall diagnostic accuracy of SCys-C for AKI in adults,and further explore possible factors affecting its performance.[Study Design]Meta-analysis of diagnostic test studies.[Setting&Population]Various clinical settings of AKI,including patients after cardiac surgery,patients exposed to contrast agent,critically ill patients and so on.[Selection Criteria]A computerized search of PubMed,Embase,Web of Science and the Cochrane Library was performed to identify potentially relevant articles.Setting search time from the beginning of database built to Sept.20,2016.The inclusion and exclusion criteria were used to filter studies.[Index Tests]Increased SCys-C level.[Reference Tests]The outcome was the development of AKI,primarily based on serum creatinine level(definition criteria varied across included studies).[Results]A total of 30 prospective cohort studies(involving 4247 adults from 15 countries,982 patients occurring AKI)were included.The revised Quality Assessment for Studies of Diagnostic Accuracy(QUADAS-2)tools demonstrated no significant bias had influenced the methodological quality of the included studies.Across all settings,the area under the curve for the receiver operating characteristic curve(AUROC)of SCys-C to predict AKI was 0.89(95%confidence interval,95%CI,0.86-0.91).The detailed assessment parameters,such as sensitivity,specificity,positive likelihood ratio,negative likelihood ratio and diagnostic odds ratio for SCys-C were 0.82(95%CI,0.75-0.87),0.82(95%CI,0.78-0.86),4.6(95%CI,3.6-5.9),0.22(95%CI,0.16-0.31)and 21(95%CI,12-35),respectively.Subgroup analysis showed in terms of the study population,SCys-C was of best diagnostic value in the contrast-induced nephropathy with AUROC was 0.90(95%CI,0.88-0.93),DOR was 61(95%CI,10-388),sensitivity was 0.90(95%CI,0.81-0.98),specificity was 0.87(95%CI,0.82-0.90).While among patients after cardiac surgery,the AUROC of SCys-C for AKI was 0.89(95%CI,0.86-0.91),the sensitivity and specificity were 0.81(95%CI,0.71-0.89),0.82(95%CI,0.72-0.89),respectively,and the I2 was 0 from all results.For diagnostic criteria for AKI,the diagnostic value of the KDIGO criteria was better than the other two criteria,and the value(AUROC,sensitivity,specificity)is 0.92,0.78 and 0.90,respectively.What's more,the diagnostic performance of Scys-C is different in subgroup restricted by the race,Scys-C assay method and so on.[Conclusion]SCys-C could be a vital promising marker to screen out all-cause AKI.The various study population,different diagnostic criteria for AKI,different SCys-C assay methods,etc.may be the influence factors of SCys-C for the diagnosis of AKI.And in patients after cardiac surgery,the predictive accuracy was high and the results were not affected by heterogeneity.[Background]Acute kidney injury(AKI)after coronary artery bypass grafting(CABG)surgery is associated with adverse in-hospital and long-term outcomes.Serum cystatin C(SCys-C)level after operation has been identified as a novel biomarker to determine AKI after cardiac surgery depended on cardiopulmonary bypass(CPB).This study was aimed to explore diagnostic accuracy of SCys-C in patients under off-pump CABG(OPCABG)and then investigate the ability to evaluate the risk in AKI occurred in this population.[Methods]495 patients assayed the post-operation SCys-C level and 697 patients assayed the pre-operation SCys-C level,who operated for OPCABG at our hospital from 2008 to 2015 were enrolled for participation in this retrospective study.Excluding criteria:age<18 years,previous AKI,pre-surgical dialysis treatment,in emergency surgery,with the evidence of end stage renal disease(ESRD)and the death of patients within 24 hours of intra-operation or post-operation.AKI was defined according to an increase in SCr>0.3mg/L within 48h,and/or an increase SCr to 1.5 times baseline,which is known or presumed to have occured within the prior 7 days.SCys-C levels were measured before operation using particle-enhanced turbidimetric immunoassay.[Results]In the first population,91(18.4%)participants developed AKI during hospitalization.Compared with non-AKI,the age of patints trends to older,and the levels of pre-operation SCys-C,post-operation SCys-C and SCr were higher in AKI group.Receiver operating characteristic(ROC)plots of SCys-C about 4-5 days after operation demonstrated that the area under the curve(AUC)for pre-surgical AKI was 0.77(95%CI,0.71-0.82,p<0.001),while SCr showed the high AUC(0.85 vs.0.77,p<0.01).In the second population,126(18.2%)participants developed AKI during hospitalization.The age of all patients was 66(60-71)years(median(interquartile range));78.8%of patients was male;SCys-C was 1.09(95%confidence interval,95%CI,0.96-1.24)mg/L;SCr was 0.88(95%CI,0.76-1.01)mg/dL;estimated glomerular filtration rate(eGFR)base on SCr(eGFRSCr)was 87.06(95%CI,73.65-95.30)mL/min/1.73m2;eGFR based on SCys-C(eGFRCys)was 66.37(95%CI,55.94-81.13)mL/min/1.73m2;eGFR based on SCr and SCys-C(eGFRscr-Cys)was 76.17(95%CI,63.96-87.97)mL/min/1.73 m2.Adjusted odds ratio in quintile 3 and 4 for SCys-C were 2.72(95%CI,1.39-5.36,p=0.004),3.82(95%CI,1.87-7.80,p<0.001),respectively,while only quintile 4 for SCr was in significance:2.89(95%CI,1.60-5.20,p<0.001).ROC plots of SCys-C demonstrated that AUC for post-surgical AKI was 0.71(95%CI,0.66-0.76,p<0.001).The cutoff value for the highest Yoden index of AKI was>1.13mg/L.In addition,compared with SCr,SCys-C performed well in AUC(0.71 vs.0.65,p=0.009),but had no statistic significance in comparison with eGFRscr,eGFRCys and eGFRsCr-Cys.Age older than 65 years old(OR=2.14,95%CI,1.50-3.07,p<0.001),BMI(OR=1.06,95%CI,1.01-1.12,p=0.03),hyperuricemia(OR= 1.58,95%CI,1.03-2.44,p=0.005),decrease of EF value(OR=0.97,95%CI,0.94-0.99,p=0.01)and increase of SCr(OR=228.30,95%CI,72.79-716.09,p<0.001)were the independent risk factors for elevated SCys-C.[Conclusion]The diagnostic accuracy of SCr is stronger than SCys-C between 4-5 days after OPCABG.The increase of SCys-C has higher value than SCr in the evaluation of AKI after OPCABG and age>65 years,BMI,hyperuricemia,decrease of EF value,and increase of SCr are independent risk factors for elevated SCys-C.