Treatment Response Rates and Kidney Outcomes among Adults with Primary FSGS

Key Points Among 228 FSGS patients treated with immunosuppression, only 55% achieved remission with relapse rates of 63% and 74% by 2 years. Over a median follow-up of 4 years, 39% of FSGS treated patients progressed to kidney failure, and a total of 27% died. Nonresponders to immunosuppression had a >2-fold risk of kidney failure compared with responders. Background FSGS has a variable response to immunosuppressive (IS) therapy and high relapse rates. Lack of US Food and Drug Administration–approved therapies underscore the need for real-world evidence to better understand treatment patterns and outcomes. This study aimed to evaluate treatment response, relapse patterns, and kidney outcomes among patients with primary FSGS. Methods A retrospective cohort study was performed within 14 medical centers of an integrated health system. Patients (18 years or older) with biopsy-confirmed primary FSGS treated with IS between 2010 and 2021 were included. Treatment response, assessed at up to 8 months, was categorized as complete remission: urine protein-to-creatinine ratio (UPCR) <0.3 g/g, partial remission: UPCR decline >50% from baseline and between 0.3 and 3.5 g/g, and no remission. Relapse was defined as loss of remission within 2 years. Outcomes, including ESKD (treatment with dialysis or transplant) and mortality, were analyzed using Fine-Gray subdistribution hazard ratio (sHR) models. Results Among 228 patients treated with IS, 55% achieved remission (12% complete remission, 43% partial remission), with relapse rates of 63% and 75% by 2 years. The median follow-up was 4 years (interquartile range, 2.0–7.6), during which 88 (39%) progressed to ESKD. A total of 62 (27%) patients died, with 33 (15%) deaths occurring before reaching ESKD. Nonresponders had a higher risk of ESKD compared with responders (sHR, 2.22; 95% confidence interval [CI], 1.41 to 3.49). Baseline eGFR <30 ml/min per 1.73 m 2 was strongly associated with risk of ESKD (sHR for eGFR of <30 versus 60+, 4.74; 95% CI, 2.24 to 10.05; P < 0.001), while baseline proteinuria (UPCR >3.5 g/g) was NS. Asian/Pacific Islander patients exhibited the highest ESKD risk among racial/ethnic groups (sHR, 2.03; 95% CI, 1.07 to 3.84). Conclusions Approximately half of FSGS patients achieved remission with IS, but relapse rates were high, and nearly 40% progressed to ESKD. Nonresponders and low baseline eGFR had the highest risk. These findings underscore the need for novel therapies to achieve durable disease control, lower relapse rates, and improve outcomes in FSGS.