Proteinuria Trajectory and Disease Progression in Children and Adults with IgA Nephropathy/Vasculitis

Key Points Defining risk of kidney function loss in IgA nephropathy and IgA vasculitis with nephritis is important for patient counseling and risk-based enrollment of clinical trials. Proteinuria trajectory over 2 years can uniquely identify patients at risk of loss of kidney function or kidney failure. Children and adults with the highest levels of proteinuria had a higher risk of progressive kidney disease compared with those with intermediate levels. Background Identifying patients with IgA nephropathy at risk of disease progression is critical for clinical decision making, risk-based patient counseling, and optimal enrollment of clinical trials. Methods Patients with IgA nephropathy and IgA vasculitis with nephritis were enrolled in the Cure Glomerulonephropathy Network, a multicenter observational cohort study. Children and adults were analyzed separately in four cohorts: ( 1 ) full, ( 2 ) incident, ( 3 ) prevalent, and ( 4 ) histology. Groups were defined using latent class trajectory modeling using proteinuria measurements over 2 years. Linear mixed models were used to calculate predicted eGFR slope. In adults, Cox proportional hazard models were used to model time to kidney failure or 40% eGFR decline as a function of the proteinuria trajectory group. Results Of 919 patients with IgA nephropathy/IgA vasculitis with nephritis enrolled into the Cure Glomerulonephropathy Network, 368 adults and 234 children were included in the analysis. In the full adult cohort, group 1 had the lowest levels of proteinuria (interquartile range [IQR], 0.1–0.4 g/g), while groups 2 and 3 had intermediate and higher levels of proteinuria (IQR, 0.5–1.5 and IQR, 1.8–4.1 g/g), respectively. The average predicted time to eGFR <15 ml/min per 1.73 m 2 was >90, 16, and 8 years and >90, 67, and 11 years for proteinuria trajectory groups 1, 2, and 3 in the full adult and pediatric cohorts, respectively. In adults, adjusting for age, eGFR at enrollment, immunosuppression exposure, and hypertension, group 3 membership was associated with 3.13 (95% confidence interval [CI], 1.84 to 5.33), 1.98 (95% CI, 0.97 to 4.06), and 3.36 (95% CI, 1.59 to 7.13) times higher hazard of progressing to a composite outcome compared with group 2 membership in the full, prevalent, and histology cohorts, respectively, but not associated with progression in the incident cohort. Conclusions Proteinuria trajectory is a major predictor of disease progression in patients with IgA nephropathy.