Early diagnosis of minimal change disease (MCD) in nephrotic syndrome (NS) patients remains challenging. Doctors often make a diagnosis of MCD using invasive renal biopsy. CD80, a transmembrane protein, is present on podocytes in a number of experimental models of NS. Urinary CD80 levels are significantly elevated in MCD but not in focal segmental glomerulosclerosis (FSGS) or other glomerulopathies. The purpose of this study was to investigate the feasibility of using urinary CD80 levels as a biomarker for the diagnosis of MCD. A total of 165 subjects, 129 men and 36 women, were enrolled in this study. Urinary samples were collected from 37 patients with MCD, 27 patients with FSGS, 30 patients with other glomerulopathies, and 71 healthy people. Using ELISA, experimental values were compared with those produced by kidney biopsy samples. The concentration of urinary CD80 was significantly higher in the active MCD group (689.66 +/- 378.21 ng/g creatinine) than in the FSGS group (123.49 +/- 167. 88 ng/g creatinine, P < 0.00), other glomerulopathies group (152.37 +/- 220. 14 ng/g creatinine, P < 0.001) and the control group (81.83 +/- 23.01 ng/g creatinine; P < 0.001). A cutoff value of 328.98 (ng/g creatinine) was proposed, with a sensitivity of 81.1 % and specificity of 94.4 %. The area under the receiver operating characteristic (ROC) curve for the urinary CD80 to diagnose MCD was 0.925 (95 % confidence interval: 0.873-0.978). This experiment has preliminarily confirmed urinary CD80 as a non-invasive diagnostic biomarker. It may have significant value in the diagnosis of MCD.