Response to immunosuppressive therapy (IS) varies among patients with focal segmental glomerulosclerosis (FSGS), and the relapse rate among that patient population is high. There are no FDA-approved therapies for FSGS, creating a need for real-world evidence to clarify treatment patterns and outcomes.
John J. Sim, MD, and colleagues conducted a retrospective cohort study to examine treatment response, patterns of relapse, and kidney outcomes among individuals with primary FSGS.
The study was conducted at 14 medical centers of an integrated health system. Eligible participants were aged 18 years or older and had biopsy-confirmed primary FSGS treated with IS between 2010 and 2021. Treatment response was categorized as: (1) complete remission (urine protein-to-creatinine ratio [UPCR] <0.3 g/g); (2) partial remission (UPCR decline >50% from baseline and between 0.3 and 3.5 g/g); and (3) no remission. Treatment response was assessed for up to 8 months after study eligibility. Researchers defined relapse as loss of remission within 2 years.
The study used Fine-Gray subdistribution hazard ratio (sHR) models to analyze the outcomes of interest, which were end-stage kidney disease (ESKD) treated with dialysis or kidney transplant, and mortality.
The cohort included 228 patients. Of those, 55% achieved remission (12% complete remission and 43% partial remission), with corresponding relapse rates of 63% and 75% by 2 years. During a median follow-up of 4 years, 39% (n=88) of patients progressed to ESKD, and 62 patients (27%) died, with 33 deaths occurring prior to reaching ESKD. The rate of ESKD was higher among nonresponders compared with responders (sHR, 2.22; 95% CI, 1.41-3.49).
There was a strong association between baseline eGFR and the risk for ESKD (sHR for eGFR of <30 vs 60+ mL/min/1.73 m2, 4.74; 95% CI, 2.24-10.05; P<0.001). Baseline proteinuria (UPCR >3.5 g/g) was nonsignificant. Among racial subgroups, the highest risk for ESKD was seen in Asian/Pacific Islander patients (sHR, 2.03; 95% CI, 1.07-3.84).
In summary, the authors wrote, “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.”