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 (2mg/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 less than 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.