Key Points:
In our US real-world cohort study of patients with IgA nephropathy, elevated proteinuria and progression to kidney failure (KF) were associated with a higher risk of cardiovascular disease/mortality events.
Elevated pre-KF proteinuria was also associated with progression to KF/mortality events.
Incremental costs associated with CKD stage, nephrotic syndrome, and cardiovascular disease events and of these events were high.
Background: IgA nephropathy (IgAN)–associated glomerular injury leads to proteinuria, hematuria, and progressive loss of GFR, 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 noninterventional, retrospective cohort study in adult patients with IgAN using Optum's deidentified Market Clarity Data (January 1, 2007, to March 31, 2021). Adult (age ≥18 years) patients with at least two signs, disease, symptoms natural language processing term entries for IgAN, within 180 and ≥30 days apart within the identification period were included. Outcomes were assessed by time-dependent proteinuria (≥1 versus <1 g/d) and KF status (pre versus 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: Patients with pre-KF status and proteinuria ≥1 g/d were more likely to have a CVD/mortality event during follow-up (adjusted hazard ratio [HR; 95% confidence interval (CI)]: 1.80 [1.12 to 2.89]; P < 0.001) or a KF/mortality event (adjusted HR [95% CI]: 2.10 [1.73 to 2.56]; P < 0.001). Patients with post-KF status were more likely to have a CVD/mortality event during follow-up (adjusted HR [95% CI]: 3.28 [2.82 to 3.81]; P < 0.001).
Conclusions: Elevated proteinuria and progression to KF were associated with a higher risk of CVD/mortality events. Elevated pre-KF proteinuria was also associated with progression to KF/mortality events. On the basis of 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.