Prediction and Risk Stratification of Kidney Outcomes in IgA Nephropathy

Abstract

Rationale & Objective: Immunoglobulin A nephropathy (IgAN) is common worldwide and has heterogeneous phenotypes. Predicting long-term outcomes and stratifying risk are important for clinical decision making and designing future clinical trials. Study Design: Multicenter retrospective cohort study of 2,047 patients with IgAN. Setting & Participants: Derivation and validation cohorts composed of 1,022 Chinese patients with IgAN from a single center and 1,025 patients with IgAN from 18 renal centers, respectively. Predictors: 36 characteristics, including demographic, clinical, and pathologic variables. Outcomes: Combined event of end-stage kidney disease or 50% reduction in estimated glomerular filtration rate within 5 years after diagnostic kidney biopsy. Analytical Approach: A gradient tree boosting method implemented in the eXtreme Gradient Boosting (XGBoost) system was used to select the 10 most important variables from 36 candidate variables. Stepwise Cox regression analysis was used to derive a simplified scoring scale model (SSM) based on these 10 variables. Model discrimination and calibration were assessed using the C statistic and Hosmer-Lemeshow test. Risk stratification of the SSM was evaluated using Kaplan-Meier analysis. Results: In the derivation and validation cohorts, 74 and 114 patients reached the outcome, respectively. XGBoost predicted the outcome with a C statistic of 0.84 (95% CI, 0.80-0.88) for the validation cohort. The SSM included 3 variables: urine protein excretion, global sclerosis, and tubular atrophy/interstitial fibrosis. Using Kaplan-Meier analysis, the SSM identified significant risk stratification (P < 0.001). Limitations: Retrospective study design, application for other ethnic groups needs to be verified. Conclusions: A prediction model using routinely available characteristics and based on the combination of a machine learning algorithm and survival analysis can stratify risk for kidney disease progression in the setting of IgAN. An online calculator, the Nanjing IgAN Risk Stratification System, permits easy implementation of this model.