Treatment Response Rates and Kidney Outcomes among Adults with Primary Focal Segmental Glomerulosclerosis

Background: Focal segmental glomerulosclerosis (FSGS) has a variable response to immunosuppressive therapy (IS) and high relapse rates. Lack of 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) with biopsy-confirmed primary FSGS treated with IS between 2010 and 2021 were included. Treatment response, assessed at up to eight months, was categorized as complete remission (CR): urine protein-to-creatinine ratio (UPCR) 50% from baseline and between 0.3–3.5g/g; and, no remission (NR). Relapse was defined as loss of remission within two years. Outcomes, including end-stage kidney disease (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% CR, 43% PR), with relapse rates of 63% and 75% by two years. 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. Non-responders had a higher risk of ESKD compared to responders (sHR: 2.22; 95% CI: 1.41, 3.49). Baseline estimated glomerular filtration rate (eGFR) 3.5 g/g) was not significant. Asian/Pacific Islander patients exhibited the highest ESKD risk among racial/ethnic groups (sHR: 2.03; 95% CI:1.07, 3.84). Conclusions: Approximately half of FSGS patients achieved remission with IS, but relapse rates were high, and nearly 40% progressed to ESKD. Non-responders 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.