Steroid-resistant idiopathic childhood nephrosis: overdiagnosed and undertreated

Abstract

The rate of complete remission after induction therapy for steroid-resistant nephrotic syndrome (SRNS) due to either focal segmental glomerulosclerosis (FSGS) or minimal change nephrotic syndrome (MCNS) has been reported to be <50%. The present retrospective study investigated 86 children with SRNS due to FSGS and MCNS and found improved rates of complete remission in children with idiopathic FSGS and MCNS after combination therapies using ciclosporin A (CSA) and prednisolone (PRED). Eighty-six children with FSGS or MCNS and with SRNS receiving standard oral PRED therapy were analysed in a retrospective, non-randomized study. Fifty-two patients had idiopathic FSGS (group 1), 14 patients had MCNS (group 2), and 20 patients had genetic FSGS or syndrome-associated FSGS (group 3). In group 1A (n = 25), induction therapy consisted of CSA (initial dose 150 mg/day/m(2) divided into two doses) given in combination with intravenous methylprednisolone (IV-MPRED 300-1000 mg/day/m(2) for 3-8 days) and oral PRED. In group 1B (n = 27), CSA was combined with oral PRED (40 mg/m(2) on alternate days). In group 1, patients with idiopathic FSGS receiving IV-MPRED + oral PRED + CSA had a significantly better outcome than patients treated with oral PRED + CSA (84 vs 64% cumulative proportion of sustained complete remission, respectively; P = 0.02, log-rank test). Sixteen (40%) out of 40 children entering complete remission had a first relapse after a median interval of 1 year. All relapses were successfully treated with IV-MPRED + oral PRED + CSA or oral PRED + CSA. Three out of forty responding children developed stage 2 chronic kidney disease (CKD), and none advanced to stage 3-5; in contrast, 9 out of 12 children with persistent nephrotic syndrome (NS) developed CKD stage 2-5 (8 vs 75%, respectively; P < 0.001, Fisher's exact test). In group 2, all 14 children with steroid-resistant MCNS went into remission after receiving PRED + CSA (n = 11) or IV-MPRED + oral PRED + CSA (n = 3). No patient developed CKD. In group 3, NS persisted in all 20 children having a genetic or syndromic type of FSGS receiving either PRED + CSA (n = 9) or PRED alone (n = 11). Seventeen out of 20 patients entered stage 5 CKD and were successfully transplanted; one patient developed recurrent NS. Prolonged and intensified treatment of children with idiopathic non-genetic SRNS (FSGS or MCNS) with combined PRED + CSA therapy including IV-MPRED pulses resulted in a higher rate of remission when compared with previous reports on using CSA mono-therapy or other immunosuppressive combination therapies.