Steroid-resistant nephrotic focal segmental glomerulosclerosis: a treatable disease

Abstract

If not aggressively treated, oral steroid-resistant (SRst) nephrotic focal segmental glomerulosclerosis (FSGS) is likely to progress to end-stage renal failure. Three observations challenge the conclusion of the International Study of Kidney Diseases in Children (ISKDC) that SRst FSGS is unresponsive to further immunosuppression: (1) The ISKDC definitions of response and relapse, which fit the patterns in minimal change disease, precluded appropriate recognition of partial or gradual responses. (2) In two ISKDC studies, a small number of children with FSGS in one case, and the use of a year of alternate-day prednisone as a control in the other, may have obscured the effects of cyclophosphamide. (3) Recent studies of more aggressive therapies have provided strong evidence of benefit. High-dose methylprednisolone infusion therapy, with alternate-day prednisone alone or with alternate-day prednisone plus an alkylating agent (the M-P/ triple therapy protocol) has achieved sustained, complete remissions with stable renal function in 66% of children with SRst FSGS, and near-complete resolution of proteinuria in another 9%. Cyclosporine (CsA) plus alternate-day prednisone has produced complete or near-complete remissions in 35% of similar cases. Whether or not controlled studies will confirm the apparently greater efficacy of the M-P/triple therapy protocol, the favorable outcomes with both the M-P and the CsA regimens support the conclusion that a conservative approach to SRst FSGS is no longer appropriate.

Efficacy of intravenous pulse cyclophosphamide treatment versus combination of intravenous dexamethasone and oral cyclophosphamide treatment in steroid-resistant nephrotic syndrome

“…Tune et al showed beneficial results in 65% patients treated with multiple i.v. pulses of methylprednisolone, cyclophosphamide orally for 8-12 weeks, and tapering doses of prednisone over 30 months [5,6]. In view of significant steroid toxicity and need for several admissions for the infusions, many centers have used shorter protocols with comparable benefit, ranging between 30%and70% [3,15].…”

“…Tune et al proposed the intravenous (i.v.) use of high doses of corticosteroids combined with oral administration of cyclophosphamide with satisfactory results [5,6]. This regimen requires multiple hospital admissions and monitoring for corticosteroid side effects.…”

Cyclosporin A is superior to cyclophosphamide in children with steroid-resistant nephrotic syndrome—a randomized controlled multicentre trial by the Arbeitsgemeinschaft für Pädiatrische Nephrologie

“…CPH therapy and found no significant difference [17]. Steroid resistance in SRNS may be relative and, in some children, can be overcome with high-dose methylprednisolone (MPR) usually in combination with CPH or CSA [18][19][20][21]. Azathioprin and chlorambucil seem to be without therapeutic effect [12].…”

Influence of nephrotic state on the infectious profile in childhood idiopathic nephrotic syndrome

“…Five steroid-resistant patients were treated with cyclophosphamide pulse therapy and methylprednisolone, associated with prednisone, according to the protocol of Tune and Mendonza. 9 The patients were divided into 2 groups according to their initial response to the steroid therapy: Group I (steroid-responsiveresolution of the proteinuria during the first 4 weeks of continuous daily treatment with prednisone) and Group II (steroid-resistant-no response to the continuous daily treatment with prednisone for 6 weeks). Group I was further divided into 4 subgroups: IA (single episode-without recurrences), IB (infrequent relapsers-less than 2 recurrences in the 6 months after the initial response), IC (frequent relapsers-2 or more recurrences in the 6 months after the initial response), and ID (steroiddependent-recurrence during the gradual withdrawal of prednisone or 15 days after its suspension).…”