Calcineurin Inhibitors With Reduced-Dose Steroids as First-Line Therapy for Focal Segmental Glomerulosclerosis

High-dose corticosteroids remain the first-line therapy for focal and segmental glomerulosclerosis (FSGS), whereas calcineurin inhibitors (CNIs) are reserved for those patients resistant to corticosteroid therapy.

This is a retrospective cohort analysis in patients with primary FSGS diagnosed between 2007 and 2014. According to the administered treatment, patients were segregated into 3 groups: high-dose prednisone, first-line CNIs plus low-dose prednisone, and rescue CNIs. Cumulative corticosteroid doses were compared as well as response to therapy and long-term renal survival by Cox regression analysis.

A total of 66 patients were included (39 treated with high-dose prednisone, 11 treated with first-line CNI, 16 treated with high-dose prednisone followed by rescue CNI). Cumulative doses of prednisone in the high-dose group were 9.3 g (interquartile range [IQR] = 7.5-12.5 g), compared to 2.5 g (IQR = 1.82-3.12 g) in the first-line CNI plus low-dose corticosteroid group and 13.8 g (IQR = 9.2-15.8 g) rescue CNI groups, respectively (P < 0.001). Time under corticosteroid management was also higher in the high-dose prednisone group compared to the first-line CNI group. There was a response to treatment in 76.9%, 72.7%, and 87.5% of high-dose prednisone, first-line CNI and rescue CNI groups, with complete remission in 48.7%, 36.4%, and 31.3% respectively. There was no difference in relapse incidence after treatment (48.4%, 44.4%, and 46.7%) or in 5-year renal survival (87.2%, 81.8%, and 87.5%). Baseline proteinuria, biopsy chronicity score, and response to therapy were independent predictors of renal survival.

An initial CNI plus low-dose corticosteroid approach in primary FSGS reduces corticosteroid exposure with a response-to-therapy rate similar to that of the currently recommended high-dose corticosteroid regimen. These findings justify a randomized trial to formally test this hypothesis.