Association of steroid and cyclosporin resistance in focal segmental glomerulosclerosis

Given the variable response of steroid-resistant nephrotic syndrome (SRNS) to treatment with cyclosporin (CsA), it may be inappropriate to expose all SR patients to additional immunosuppression. How to determine from which patients to withhold CsA is unclear. We tested the hypothesis that in patients with primary focal segmental glomerulosclerosis (FSGS), steroid resistance predicts CsA resistance. We studied 16 children with steroid-dependent (SD) or steroid-resistant (SR) histologically confirmed primary FSGS treated with CsA with no prior exposure to other immunosuppressive medications. All had received at least 4 weeks of daily prednisone, followed by addition of CsA aiming at trough levels of 200 ng/ml. Of the 16 patients, nine (56%) were SR, of whom seven (78%) were CsA resistant and two (22%) were CsA responsive. Seven patients (44%) were SD; all of them (100%) were CsA responsive (P = 0.003, Fisher's exact test). SR patients had faster deterioration of glomerular filtration rate (GFR) over a median follow-up of 21 months (P = 0.06). These data demonstrate that in primary FSGS, steroid resistance may predict CsA resistance. Genetic testing for known mutations associated with resistance to immunosuppression may be advisable before treatment of SR-FSGS patients with cyclosporin. Prospective studies should be conducted to explore this hypothesis.