Clinical trial of focal segmental glomerulosclerosis in children and young adults

Abstract

This NIH-funded multicenter randomized study of focal segmental glomerulosclerosis (FSGS) treatment compared the efficacy of a 12-month course of cyclosporine to a combination of oral pulse dexamethasone and mycophenolate mofetil in children and adults with steroid-resistant primary FSGS. Of the 192 patients enrolled, 138 were randomized to cyclosporine (72) or to mycophenolate/dexamethasone (66). The primary analysis compared the levels of an ordinal variable measuring remission during the first year. The odds ratio (0.59) for achieving at least a partial remission with mycophenolate/dexamethasone compared to cyclosporine was not significant. Partial or complete remission was achieved in 22 mycophenolate/dexamethasone- and 33 cyclosporine-treated patients at 12 months. The main secondary outcome, preservation of remission for 26 weeks following cessation of treatment, was not significantly different between these two therapies. During the entire 78 weeks of study, 8 patients treated with cyclosporine and 7 with mycophenolate/dexamethasone died or developed kidney failure. Thus, our study did not find a difference in rates of proteinuria remission following 12 months of cyclosporine compared to mycophenolate/dexamethasone in patients with steroid-resistant FSGS. However, the small sample size might have prevented detection of a moderate treatment effect.

Circulating suPAR in Two Cohorts of Primary FSGS

“…Neither the baseline nor the change in suPAR level from week 0 to week 26 predicted the outcome in the FSGS CT cohort based on the trial's original six-ordinal scale. 15 However, using multiple regression analysis, investigation of the relative changes of serum suPAR from baseline to week 26 revealed a positive association with both the absolute change (P=0.01) and percentage reduction (P=0.003) in the Up/c between the two time points when proteinuria was assessed as a continuous variable and complete or partial remission were based on the definitions of Troyanov 16 (Table 4). A logistic regression analysis that controlled for age, sex, race, eGFR, Up/c, and suPAR at baseline indicated greater odds for complete remission (Up/c #0.2 g/g achieved at least once from weeks 26 to 78) with each 10% reduction in suPAR concentration (odd ratios, 1.44; 95% confidence interval, 1.02-2.03; P=0.04) ( Table 4).…”

“…Patients were seen 11 times during the treatment period and BP was measured and blood and urine were obtained at each visit to determine serum creatinine, eGFR, albumin, and cholesterol concentrations and proteinuria. 27 The serum samples collected at baseline and 26 weeks on the experimental treatment from a group of randomly selected patients (n=35 in each arm) were retrieved from the National Institutes of Diabetes and Digestive and Kidney Diseases Biorepository for suPAR measurement. In this study, complete remission was defined as Up/c #0.2 g/g observed at least once from weeks 26 to 78.…”

Association of Histologic Variants in FSGS Clinical Trial with Presenting Features and Outcomes

“…Entry criteria included corticosteroid-resistant primary FSGS documented by renal biopsy at the referring institution and confirmed by one of the study's expert core renal pathologists. Patients were randomized to a 12-month course of either cyclosporine (CSA) or mycophenolate mofetil and dexamethasone (MMF/DEX) (1); 46% of CSA-treated patients and 33% of MMF/ DEX patients achieved at least partial remission at 1 year, whereas only 19% of CSA and 9% of MMF/DEX patients achieved complete remission (1). These outcome differences were not statistically significant.…”

“…The National Institutes of Healthfunded multicenter FSGS Clinical Trial (FSGS-CT) examined outcomes in 138 steroid-resistant children and young adults aged 2-40 years (1,2). Entry criteria included corticosteroid-resistant primary FSGS documented by renal biopsy at the referring institution and confirmed by one of the study's expert core renal pathologists.…”

Mycophenolate mofetil for primary focal segmental glomerulosclerosis: systematic review

“…Risk of bias was assessed for the three included RCTs, and details are provided in Table 2. The overall risk of bias was low in Gipson et al 44 , but unclear in Senthil Nayagam et al 24 and Xiao et al 23 Treatment outcomes…”