Clinical trials treating focal segmental glomerulosclerosis should measure patient quality of life

Abstract

Optimal therapy of patients with steroid-resistant primary focal segmental glomerulosclerosis (FSGS) remains controversial. This report describes the initial study design, baseline characteristics, and quality of life of patients enrolled in the FSGS Clinical Trial, a large multicenter randomized study of this glomerulopathy comparing a 12-month regimen of cyclosporine to the combination of mycophenolate mofetil and oral dexamethasone. Patients with age ranging 2-40 years, with an estimated glomerular filtration rate > 40 ml/min per 1.73 m², a first morning urine protein-to-creatinine ratio over one, and resistant to corticosteroids were eligible. The primary outcome was complete or partial remission of proteinuria over 52 weeks after randomization. In all, 192 patients were screened, of whom 138 were randomized for treatment. Ethnic distributions were 53 black, 78 white, and 7 other. By self- or parent-proxy reporting, 26 of the 138 patients were identified as Hispanic. The baseline glomerular filtration rate was 112.4 (76.5, 180.0) ml/min per 1.73 m², and urine protein was 4.0 (2.1, 5.3) g/g. Overall, the quality of life of the patients with FSGS was lower than healthy controls and similar to that of patients with end-stage renal disease. Thus, the impact of FSGS on quality of life is significant and this measurement should be included in all trials.

Trial registration: ClinicalTrials.gov NCT00135811.

Figure 1. Focal Segmental Glomerulosclerosis (FSGS) Clinical Trial enrollment, screening, and randomization summary

eGFR, estimated glomerular filtration rate; HTN, hypertension; Hx, history; Up/c, urine protein/creatinine ratio.

Figure 2. Focal Segmental Glomerulosclerosis (FSGS) Clinical Trial primary outcome definitions

Category 1, patients who achieved a complete remission by week 26 that was sustained to week 52; category 2, patients who achieved a partial remission at week 26 and then a complete remission at week 52; category 3, patients who achieved a partial remission by week 26 that was sustained to week 52; category 4, patients who achieved a partial remission at week 26 and then had recurrence of proteinuria before week 52; category 5, patients who achieved a partial remission before week 26 and then had a recurrence of proteinuria before week 26; category 6, patients who never had a urine protein/creatinine ratio (Up/c) <50% of the baseline value and an absolute value below 2 g/g. Participants with a baseline Up/c between 1 and 1.99 g/g were required to meet the 50% reduction in Up/c to meet the criteria of partial remission and <0.2 g/g for complete remission consistent with subjects entering with a baseline Up/c ≥2 g/g.