Cardiovascular, Kidney Failure, and All-Cause Mortality Events in Patients with FSGS in a US Real-World Database

Background FSGS leads to proteinuria and progressive decline in GFR, which correlates with kidney failure (KF) and increased cardiovascular risk. The purpose of this study was to estimate the effects of proteinuria on KF status/all-cause mortality and cardiovascular disease (CVD) events/all-cause mortality, as well as the relationship between progression to KF and occurrence of CVD/mortality events among adult patients (18 years or older) with FSGS. Methods This was an observational, retrospective cohort study utilizing Optum deidentified Market Clarity Data and proprietary Natural Language Processing data. The study period was from January 1, 2007, through March 31, 2021, with patients in the overall cohort being identified from July 1, 2007, through March 31, 2021. The index date was the first FSGS ICD-10 diagnosis code or FSGS-related natural language processing term within the identification period. Results Elevated proteinuria >1.5 and >= 3.5 g/g increased the risk of KF/all-cause mortality (adjusted hazard ratio [HR] [95% confidence interval (CI)], 2.34 [1.99 to 2.74] and 2.44 [2.09 to 2.84], respectively) and CVD/all-cause mortality (adjusted HR [95% CI], 2.11 [1.38 to 3.22] and 2.27 [1.44 to 3.58], respectively). Progression to KF was also associated with a higher risk of CVD/all-cause mortality (adjusted HR [95% CI], 3.04 [2.66 to 3.48]). Conclusions A significant proportion of patients with FSGS experience KF and CVD events. Elevated proteinuria and progression to KF were associated with a higher risk of CVD/all-cause mortality events, and elevated pre-KF proteinuria was associated with progression to KF/all-cause mortality events. Treatments that meaningfully reduce proteinuria and slow the decline in GFR have the potential to reduce the risk of CVD, KF, and early mortality in patients with FSGS.