Abstract
BackgroundPatients with resistant primary focal segmental glomerulosclerosis (FSGS) are at high risk of progression to chronic kidney disease stage V. Antifibrotic agents may slow or halt this process. We present outcomes of follow-up after a Phase I trial of adalimumab and rosiglitazone, antifibrotic drugs tested in the Novel Therapies in Resistant FSGS (FONT) study.Methods21 patients -- 12 males and 9 females, age 16.0 ± 7.5 yr, and estimated GFR (GFRe) 121 ± 56 mL/min/1.73 m2 -- received adalimumab (n = 10), 24 mg/m2 every 14 days or rosiglitazone (n = 11), 3 mg/m2 per day for 16 weeks. The change in GFRe per month prior to entry and after completion of the Phase I trial was compared.Results19 patients completed the 16-week FONT treatment phase. The observation period pre-FONT was 18.3 ± 10.2 months and 16.1 ± 5.7 months after the study. A similar percentage of patients, 71% and 56%, in the rosiglitazone and adalimumab cohorts, respectively, had stabilization in GFRe, defined as a reduced negative slope of the line plotting GFRe versus time without requiring renal replacement therapy after completion of the FONT treatment period (P = 0.63).ConclusionNearly 50% of patients with resistant FSGS who receive novel antifibrotic agents may have a legacy effect with delayed deterioration in kidney function after completion of therapy. Based on this proof-of-concept preliminary study, we recommend long-term follow-up of patients enrolled in clinical trials to ascertain a more comprehensive assessment of the efficacy of experimental treatments.
Highlights
Patients with resistant primary focal segmental glomerulosclerosis (FSGS) are at high risk of progression to chronic kidney disease stage V
There were no significant differences between the patients who were assigned to receive adalimumab or rosiglitazone
Two patients were withdrawn from the study before completing the full 16-week Treatment Period - one child assigned to rosiglitazone developed a possible drug allergy, necessitating discontinuation of the drug after 6 weeks and one adult treated with adalimumab was removed from the study after 12 weeks because of refractory edema that required alternate therapy for control
Summary
Patients with resistant primary focal segmental glomerulosclerosis (FSGS) are at high risk of progression to chronic kidney disease stage V. We present outcomes of follow-up after a Phase I trial of adalimumab and rosiglitazone, antifibrotic drugs tested in the Novel Therapies in Resistant FSGS (FONT) study. Primary focal segmental glomerulosclerosis (FSGS) is increasing in frequency throughout the world [1] It usually presents with isolated proteinuria or overt nephrotic syndrome in both pediatric and adult patients [2,3,4]. We summarize the kidney function outcomes at follow-up after completion of the Phase I study to obtain preliminary data about the legacy effect of these two drugs, namely their capacity to alter the natural history of the disease in children and young adults with refractory primary FSGS
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