The Clinical Verification And Diagnostic Value For Renal Function With EGFR Equation Based On SCysC And SCr Index

BackgroundSerum biomarkers such as serum creatinine?SCr?,serum cystatin C?SCysC?have been widely used to evaluate renal function in patients with chronic kidneydisease?CKD?,diabeticnephropathy?DN?,kidney transplant.However,Compar-ed with the gold standard,the assessment accuracy and the clinical applicability,which is to evaluate the effect of different kinds of kidney disease have not been evaluated or verified.We try to conduct a serious of meta-analysis of diagnostic tests of glomerular filtration rate?GFR?value via creatinine or cystatin C or both of them to investigate which can provide the best measure of renal function.At the same time,this research try to validate and assess the clinical applicability of eGFR equation in chronic kidney disease patients that consist of both SCysC and SCr,and the eGFR equation which is based one of SCysC or SCr.ObjectiveThis research aims to evaluate the diagnostic value of serum cystatin C and serum creatinine in patients with CKD,kidney transplant,diabetic nephropathy.This research also aims to evaluate the applicability of modified equation based on glomerular filtration rate in Chinese patients with CKD.MethodsMedline,EmBase,the Cochrane Library and other databases were searched with both MeSH terms and text words to collect studies that evaluated the diagnostic value of cystatin C and creatinine in evaluating GFR in patients with CKD,kidney transplant,diabetic nephropathy.The data were extracted into 2×2 table after the chosen articles were assessed by the tool of Quality Assessment of Diagnostic Accuracy Studies?QUADAS?.The Summary Receiver Operating Characteristic curve and meta-analysis were performed via Meta-Disc1.4 version and Stata 14.0 version.A total of 143 Chronic Kidney Disease patients were investigated.GFR was estimated with Chinese MDRD equation 1,Chinese MDRD equation 2,CKD-EPIs_cr-c_ysc equation,MDRD equation and abbreviated MDRD equation,separately.The accuracy of estimated GFRs was compared with^99mTc-DTPA-GFR?sGFR?in Chronic Kidney Disease patients.Results1.Totally,21 relevant articles about patients with chronic kidney disease wereincludedinourreview,withstudysubjectsinvolving3112patients.Meta-analysis indicated that the pooled of sensitivity for SCr and CysCwas0.77?95%CI:0.69-0.84?,0.87?95%CI:0.82-0.91?,thepooledof specificityforSCrandCysCwas0.91?95%CI:0.86-0.94?,0.87?95%CI:0.82-0.91?,Separately.Subgroup analyses showed that when the GFR cut-off values are set as 60?ml/min/1.73 m²?,the pooled of sensitivity for CysC was 0.94?95%CI:0.90-0.96?,for SCr was 0.75(95%CI:0.68-0.82.And the pooled of specificity for CysC was 0.86?95%CI:0.78-0.91?,for SCr was0.88?95%CI:0.83-0.92?,separately.TheAUCofcystatinCwasgreater(AUC^CysC=0.93?95%CI:0.91-0.95?,AUC^SCr=0.92?95%CI:0.89-0.94?),which proved the diagnostic accuracy was higher.2.Totally,12 relevant articles about patients with kidney transplant were included in our review,with study subjects involving 692 patients.Meta-analysis showed that the pooled sensitivity for SCr and CysC was0.56?95%CI:0.52-0.60?,0.65?95%CI:0.61-0.68?,the pooled specificity for SCr and CysC was 0.58?95%CI:0.51-0.65?,0.71?95%CI:0.64-0.76?,separately.The95%confidence intervals for the pooled specificity for the SCr and CysC overlap.Analysis results of CysC and SCr did not show that CysC had the greatest pooled specificity,but has a little greater pooled specificity.Moreover,compared to the AUC of creatinine,cystatin C was greater(AUC^SCr=0.6069,AUC^CysC=0.6838),which proved the diagnostic accuracy was higher.3.The initial literatures search identified 260 studies and finally 14independent studies about patients with diabetic nephropathy had been adopted in this study.Data from 14 independent studies and 1 945 cases were analyzed.Meta-analyses showed that the pooled sensitivity of CysC and SCr were0.88?95%CI:0.85-0.90?,0.78?95%CI:0.75-0.81?;and the pooled specificity was0.83?95%CI:0.81-0.85?,0.84?95%CI:0.81-0.86?.The pooled positive likelihood ratio,pooled negative likelihood ratio and the pooled diagnostic odds ratio of CysC and SCr were 5.82?95%CI:3.89-8.70?,5.14?95%CI:3.51-7.51?;0.15?95%CI:0.11-0.19?,0.25?95%CI:0.19-0.33?;and 56.34?95%CI:29.90-106.19?,24.02?95%CI:15.62-36.94?,respectively.Area under the SROC curve of CysC and SCr were(AUC^SCysC=0.9506,SE(AUC^SCysC)=0.0116),(AUC^SCr=0.8943,SE(AUC^SCr)=0.0143).Analy sis results of CysC and SCr showed that CysC had a greater pooled sensitivity,but has a similar pooled specificity.4.Bland-Altman analysis demonstrated that the GFR estimated by MDRD equation and CKD-EPIs_cr-c_ysc equation were more consistent with sGFR than the other equations.But all the eGFR were not well consistent with sGFR.Linear regressions showed that the slopes of MDRD equation and CKD-EPIs_crequation were closer to the identical line.30%and 50%accuracies of CKD-EPIs_cr-c_ysc equation were higher than the other equations.But 30%accuracy of CKD-EPIs_cr-c_ysc equation was less than 70%.When the accuracy of estimated GFRs was compared with sGFR in different stages of CKD,GFR estimated by CKD-EPIs_cr-c_ysc equation and MDRD equation showed less bias and higher accurate than other equations.Conclusions1.The diagnostic accuracy for impaired renal function favors CysC.The 95%confidence intervals for the pooled sensitivity and specificity for the SCr and CysC overlap.However,CysC is more sensitivity for the estimation of GFR than SCr when the GFR cut-off values are set as 60?ml/min/1.73 m²?.2.The diagnostic accuracy for kidney transplant favors CysC.The 95%confidence intervals for the pooled specificity for the SCr and CysC overlap,The results of the analysis of CysC and SCr do not show that CysC had the greatest pooled specificity.The cystatin C was greater,which demonstrated the diagnostic accuracy was higher for pooled specificity and sensitivity.3.CysC is useful in the valuation of glomerular filtration function and it also has a diagnostic value in the diagnosis of early diabetic nephropathy.The results of the analysis of CysC and SCr showed that CysC had a greater pooled sensitivity and similar pooled specificity.4.Instead of renal dynamic imaging determination method of^99mTc-DTPA,when the glomerular filtration rate evaluation equation only refered to the index of serum creatinine is used to evaluate eGFR,significant deviation may produce to evaluate renal function with chronic kidney disease.In order to reduce the misdiagnosis and missed diagnosis and to improve the diagnostic accuracy,but for combination with clinical symptoms,serum creatinine together with serum CysC could evaluate renal function with exactly estimated glomerular filtration rate.