Pulse methylprednisolone, cyclosporine, and ACE inhibitor therapy decreases proteinuria in two siblings with familial focal segmental glomerulosclerosis

Familial focal segmental glomerulosclerosis (FSGS) is a heterogeneous renal disease characterized by proteinuria and an unremitting deterioration of r enal excretory function. Previous studies showed corticosteroid unresponsiv eness and a variable response to cyclophosphamide therapy. We hypothesized that treatment with pulse methylprednisolone therapy (PMT), alternate-day c orticosteroids, and cyclophosphamide or cyclosporine would decrease protein uria in patients with familial FSGS. Two adolescent brothers, 13 and 16 yea rs old, presented with nephrotic range proteinuria, but with normal renal e xcretory function. Both brothers had renal biopsies that showed FSGS with m esangial hypercellularity and tubular atrophy. Intravenous PMT, at doses of 1 g, was initiated per the Tune-Mendoza protocol. Both patients received l isinopril therapy. One brother (case 1) was treated with PMT, alternate-day corticosteroids, and cyclophosphamide (total cumulative cyclophosphamide d ose was 154.3 mg/kg), Urinary protein to-urinary creatinine (UP/UC) ratios decreased from 6.79 to 3.79. Cyclosporine therapy decreased the UP/UC furth er from 2.48 to 0.76 at the end of PMT. The other brother (case 2), treated with PMT, alternate day corticosteroids, and cyclosporine, experienced a d ecrease in UP/UC from 7.27 to 1.14. At the time of last evaluation, approxi mately 7 months after the last PMT dose, the UP/UC ratios were 0.27 (case 1 ) and 0.37 (case 2). PMT-attributable adverse effects were not severe. Both patients continued to receive oral cyclosporine and lisinopril after compl etion of PMT. PMT and cyclosporine therapy may reduce proteinuria, without decreasing renal excretory function, In some patients with familial FSGS. F urther evaluation of cyclosporine therapy and PMT of patients with familial FSGS is warranted. (C) 2001 by the National Kidney Foundation, Inc.