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October 9, 2025Clinical Journal of the American Society of Nephrology1 citations

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

JSJohn J. Sim MMMercedes A. Munis BLBenjamin Lewing

Key Points

Around 55% of patients with focal segmental glomerulosclerosis achieved remission with immunosuppressive therapy, but relapse rates were notably high.
Non-responders had a significantly increased risk of progressing to end-stage kidney disease compared to responders, with a sHR of 2.22.
The study evaluated treatment response and outcomes in a diverse group of patients over a median follow-up of four years, emphasizing the need for novel therapies.
Baseline eGFR of less than 30 mL/min/1.73m² was found to strongly predict the risk of end-stage kidney disease among patients.

Abstract

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.

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