Objective:To analyze the long-term prognosis of IgA nephropathy (IgAN) with focal segmental glomerulosclerosis (FSGS) and the risk factors related to renal prognosis in children with IgAN-FSGS.Methods:A retrospective study was concluded in IgAN-FSGS children who were followed up for more than 5 years and diagnosed by renal biopsy for the first time in the Eastern Theater General Hospital from January, 2004 to December, 2018. The end-point events of the study were entering end-stage kidney disease (ESKD) or estimated glomerular filtration rate (eGFR) decreased by ≥50% from baseline, which were defined as poor renal prognosis. Baseline clinicopathologic data of IgAN-FSGS children were compared between the end-point event group and the non-end-point event group. The cumulative renal survival rate of IgAN-FSGS children was calculated by Kaplan-Meier survival analysis. The influencing factors of poor renal prognosis in IgAN-FSGS children were analyzed by Cox proportional hazards model, and the diagnostic value was evaluated by the receiver operating characteristic curve (ROC curve) and area under the curve (AUC). The diagnostic value was verified by time dependent-ROC and time dependent-AUC.Results:A total of 204 IgAN-FSGS children were enrolled in this study, of whom 132 cases were males (64.7%). The median age of renal biopsy was 16 (14, 17) years old. During a median follow-up time of 90.7 (71.7, 114.8) months, 57 cases (27.9%) reached the end-point events. Compared with the non-end-point event group ( n=147), the end-point event group ( n=57) had higher proportions of males and hypertension, higher levels of 24-hour urinary protein, serum creatinine, serum uric acid, urinary N-acetyl-β- D-glucosaminidase, urinary retinol binding protein, higher proportions of glomerular segmental sclerosis (S1) ≥25% and tubular atrophy/interstitial fibrosis (T1/T2), and lower levels of serum albumin, serum IgA, and serum IgG (all P<0.05). There was no statistical difference between the two groups in treatment (all P>0.05). Kaplan-Meier survival analysis showed that with entry of ESKD or eGFR decreased by ≥50% from baseline as the end-point events, the 5-year, 10-year, and 15-year cumulative renal survival rates in IgAN-FSGS children were 88.7%, 67.6%, and 50.7%, respectively. Multivariate Cox regression analysis showed that proteinuria >1 g/24 h ( HR=3.702, 95% CI 1.657-8.272, P=0.001), hyperuricemia ( HR=3.066, 95% CI 1.793-5.245, P<0.001), S1≥25% ( HR=2.017, 95% CI 1.050-3.874, P=0.035), T1/T2 ( HR=1.863, 95% CI 1.021-3.158, P=0.016) were the independent related factors for poor renal prognosis. ROC curve analysis showed that S1≥25% ( AUC=0.605, P=0.021, sensitivity 26.3%, specificity 94.6%), T1/T2 ( AUC=0.624, P=0.006, sensitivity 43.9%, specificity 81.0%), hyperuricemia ( AUC=0.658, P<0.001, sensitivity 52.6%, specificity 78.9%), proteinuria>1 g/24 h ( AUC=0.670, P<0.001, sensitivity 87.7%, specificity 46.3%) could accurately predict the renal outcome of IgAN-FSGS. Time dependent-ROC curve validation showed that the combined diagnosis of S1≥25%, T1/T2, hyperuricemia and proteinuria>1 g/24 h had a good predictive value for renal prognosis (3-year AUC=0.846 and 5-year AUC=0.777, respectively). Conclusions:During a median follow-up of 90.7 months, 27.9% of IgAN-FSGS children have poor renal prognosis, and the 5-year, 10-year, and 15-year cumulative renal survival rates are 88.7%, 67.6%, and 50.7%, respectively. Urinary protein >1 g/24 h, hyperuricemia, T1/T2, and S1 ≥25% are the risk factors for renal prognosis in IgAN-FSGS children.