Kidney Failure Events, Cardiovascular Disease Events and All-Cause Mortality in Immunoglobulin A Nephropathy Patients in a Real-World Database

Background: IgA nephropathy (IgAN) associated glomerular injury leads to proteinuria, hematuria, and progressive loss of glomerular filtration rate, with progression to kidney failure (KF). This retrospective study evaluated the prognostic effects of proteinuria and progression to KF on cardiovascular disease (CVD)/mortality events and KF/mortality events in the United States. Methods: We conducted a non-interventional, retrospective cohort study in adult IgAN patients using Optum’s de-identified Market Clarity Data (01/01/2007 to 03/31/2021). Adult (≥18 years old) patients with at least two signs, disease, symptoms natural language processing term entries for IgAN, within 180 days and ≥30 days apart within the identification period were included. Outcomes were assessed by time-dependent proteinuria (≥1 g/day vs. <1 g/day) and KF status (pre vs. post). Descriptive statistics were used for categorical and continuous variables. Multivariable Cox proportional hazard models with time-dependent predictors were used to estimate differences across groups. Results: Pre-KF patients with proteinuria ≥1 g/day were more likely to have a CVD/mortality event during follow-up (adjusted hazard ratio [HR; 95% CI]: 1.80 [1.12–2.89]; p<0.001) or a KF/mortality event (adjusted HR [95% CI]: 2.10 [1.73–2.56]; p<0.001). Post-KF patients were more likely to have a CVD/mortality event during follow-up (adjusted HR [95% CI]: 3.28 [2.82–3.81]; p<0.001). Conclusions: Elevated proteinuria and progression to KF was associated with higher risk of CVD/mortality events. Elevated pre-KF proteinuria was also associated with progression to KF/mortality events. Based on our real-world retrospective database analysis, we hypothesize that novel IgAN therapies that reduce proteinuria and slow the rate of progression to KF have the potential to reduce CVD risk, improve kidney outcomes and prolong/increase overall survival.