Steroid-dependent nephrotic syndrome in children: Histopathology and relapses after cyclophosphamide treatment

Abstract

Children with steroid-dependent frequently relapsing nephrotic syndrome are generally assumed to have a minimal change in histology and therefore to respond favorably to treatment with cyclophosphamide. The clinical course of 38 children with steroid-sensitive frequently relapsing nephrotic syndrome was analyzed. Biopsy samples were obtained from these children several years (mean 6 years) after the onset of their disease but before they were treated with cyclophosphamide. Three histologic types of lesions were found: minimal change lesion, 18 patients (47%); focal and segmental glomerulosclerosis, 11 patients (29%); and mesangial proliferation, 9 patients (24%). Each patient then received cyclophosphamide (2 mg/kg of body wt per day) for 12 weeks, and each responded with a complete remission, which lasted 1.5 ± 0.2 years. During 6 years of followup after cyclophosphamide, 17 patients experienced one or more relapses, but 21 patients remained in sustained remission. The incidence of relapse after cyclophosphamide was significantly greater (P<0.01) in the patients with focal and segmental glomerulosclerosis (8/11, 73%) and mesangial proliferation (5/9, 56%), as compared with children with minimal change lesion (4/18, 22%). These data indicate that children with frequently relapsing steroid-dependent nephrotic syndrome (1) will not all develop minimal-change lesions within several years; in fact, approximately half will have either focal and segmental glomerulosclerosis or mesangial proliferation; and (2) after cyclophosphamide treatment, the incidence of relapse will be related to the histopathologic type of lesion present at the time of treatment with cyclophosphamide.