Objective To investigate the significance of combined detection of urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in early diagnosis of contrast-induced nephropathy (CIN). Methods A total of 367 hospitalized patients undergone CT angiography (CTA) was enrolled into this study from May 2015 to February 2017. According to the European Society of Urology and radiology (ESUR) guidelines 2011, CIN was diagnosed in 31 patients (CIN group), and a total of 30 non CIN patients were randomly selected as non-CIN group. Another 30 patients who were hospitalized during the same period without contrast media were randomly selected as the control group. The changes of serum creatinine (Scr), urinary NGAL, KIM-1, and IL-18 were detected before and 8 h, 24 h and 72 h after CTA. The same serum and urinary samples were collected at the time of admission in the control group. The sensitivity and specificity values of combined urinary NGAL, KIM-1, and IL-18 in early diagnosis CIN were evaluated by the under area of the receiver operating characteristic curves and area under curve (AUC). Results ⑴ According to ESUR guidelines 2011, CIN was diagnosed in 31 patients (8.4%). ⑵ At 8h after CTA, the levels of urinary NGAL, KIM-1, and IL-18 were significantly increased in the CIN group, compared with non-CIN group (P<0.05). ⑶ The AUC, sensitivity and specificity for early diagnosis of CIN were 0.999, 96.8%, and 100%, when combine urinary NGAL, KIM-1, and IL-18, at 8h after CTA. AUC for 24 h, and 72 h after contrast media injection approach to 1.0, at this time sensitivity and specificity were 100%, and 100%, respectively. Conclusions ⑴ At 8 h after CTA, the urinary NGAL, KIM-1, and IL-18 levels were significantly increased in the CIN group. ⑵ The predictable time of CIN onset determined by urinary NGAL, KIM-1, and IL-18 was earlier than Scr, and the sensitivity and specificity is higher in these biomarkers than Scr in early diagnosis of CIN. Especially combination of urinary NGAL, KIM-1, and IL-18 is more valuable in predicting the sensitivity and specificity of the diagnosis, and can be used as an indicator for early diagnosis of CIN. Key words: Apolipoproteins/UR; Interleukin-18/UR; Membrane glycoproteins/UR; Nephrosis/DI