To Explore The Changes Of Urinary NGAL, IL-18 And KIM-1 After CAG And PCI, And Evaluate The Implication In Early Diagnosis Of CIN

Objective:To explore the changes of urinary Neutrophil Gelatinase Associated Lipocalin(NGAL), Interleukin-18(IL-18) and Kidney Injury Molecule-1 (KIM-1) after coronary angiography(CAG) and percutaneous coronary intervention(PCI) in a prospective study, and evaluate the implication of them in early diagnosis of Contrast-induced nephropathy(CIN).Methods:One hundred and sixty patients undergone CAG and PCI were enrolled in this study, and CIN was defined following the traditional criteria. Patients identified with CIN were taken as CIN group. The patients of the control group(non-CIN group) were pair matched with cases at an attempted 2:1 ratio by age, gender, post-procedure infusion amount 24h after the procedure, baseline SCr and also contrast volume. SCr were measured before and 24h,48h and 72h after the procedure. Before and 4h,12h and 24h after the procedure, urine samples were collected. Urinary NGAL, IL-18 and KIM-1 were measured by using enzyme linked immune sorbent assay(ELISA) kits respectively and were compared between before and after the procedure as well as between CIN and non-CIN groups.Results:1. CIN occurred in 14 of 160 enrolled patients, and the incidence was 8.7%.2.4h after the use of contrast medium the values of urinary NGAL(ng/ml) were significantly higher in the CIN patients as compared with the non-CIN patients[14.17(12.64,14.85) vs.11.35(9.25,12.25), P<0.05]; the values of urinary NGAL ranged from 9.65(7.92,10.55)ng/ml to 14.17(12.64,14.85)ng/ml and were significantly increased from the basaline values to 4h after the procedure in the CIN group(P<0.05).3.12h after the procedure, compared with the non-CIN group, urinary IL-18(ng/L) concentrations of CIN group elevated significantly [58.03(53.15,64.91) vs. 50.10(44.19,53.42), P<0.05]; the urinary IL-18(ng/L) concentrations were significantly increased [58.03(53.15,64.91) vs.43.62(38.63,51.38), P<0.05]from the basaline to 4h after the procedure in the CIN group.4.24h after the CAG or PCI procedure, compared with the non-CIN group, urinary KIM-1(ng/ml) levels of CIN group increased significantly [5.21(4.86,5.42) vs.4.33(4.06,4.63), P<0.05]; the urinary KIM-1 (ng/ml) levels were significantly increased [5.21(4.86,5.42) vs.3.81(3.54,4.32), P<0.05]from the basaline values to 24h after the procedure in the CIN group.5. The significant linera correlation was found between the levels of urinary NGAL and SCr (r=0.814, P<0.05) in the CIN group, so did the urinary IL-18(r=0.652, P<0.05) and KIM-1(r=0.758, P<0.05).6. Receiver operating characteristic(ROC) curve analysis showed that the area under the ROC curve(AUC) for urinary NGAL was 0.897. When the cut-off value of NGAL were set at 11.95ng/ml, the sensitivity and specificity for the diagnosis were 92.9% and 71.4% respectively; the AUC for urinary IL-18 was 0.745. Using a cut-off value of 53.66ng/L, the sensitivity and specificity for prediction of CIN were 71.4% and 78.6% respectively; the AUC for urinary KIM-1 was 0.839. With the cut-off value of urinary KIM-1 as 4.595ng/ml, the diagnostic sensitivity and specificity in CIN were 85.7% and 71.4% respectively.Conclusion:1. Urinary NGAL may be a good biomarker for early diagnosis of CIN which can indicate the acute kidney injury(AKI) after 4h using the contrast medium.2. Urinary IL-18 and KIM-1 can reflect the change of renal function after contrast injection earlier than serum creatinine and may be good biomarkers for early diagnosis of CIN.