Evaluating the long-term risk of kidney failure in IgA nephropathy using a real-world population-level cohort from Canada

Background The population-level epidemiology of IgA nephropathy (IgAN), long-term ESKD risk, and identification of low-risk subgroups using proteinuria or the International IgAN Prediction Tool all remain unknown. Methods Using a population-level cohort of 1,382 adults with IgAN over 21 years in British Columbia (36/30/26% White, East Asian, Filipino/South Asian) we estimated incidence, prevalence, standardized mortality ratio (SMR), and long-term ESKD including based on categories from the Prediction Tool. Results The incidence and prevalence were 2.03 (95% CI 1.92, 2.14) per 100,000/year and 31.03 (95% CI 29.19, 32.87) per 100,000. The mortality risk was increased (SMR 1.79, 95% CI 1.54, 2.07) including prior to ESKD. The 20-year ESKD risk approached 50-60% in all age groups but was <10% in those with proteinuria <0.5 g/d and eGFR ≥60 ml/min/1.73 m 2 , or 0.5-1 g/day and eGFR ≥90 ml/min/1.73m 2 . Predicted risk from the Tool was associated with increasing 20-year ESKD risks (22% to 93%, P<0.001), and faster eGFR decline (1.6 to 8.1 ml/min/1.73 m 2 /year, P = 0.001); 22% of patients had predicted risk <6% with 20-year ESKD risk of 5% (95% CI 2, 12). Conclusion In a population-based multi-ethnic cohort of unselected patients with IgAN, the mortality risk is increased compared to the general population. Although ESKD risk is substantial in all age groups, those with preserved kidney function and low proteinuria are unlikely to experience ESKD. The Prediction Tool is correlated with long-term ESKD and can identify nearly one quarter of patients with predicted risk <6% who are unlikely to experience ESKD.