Steroid-Responsive Nephrotic Syndrome of Childhood: A Long-Term Study of Clinical Course, Histopathology, Efficacy of Cyclophosphamide Therapy, and Effects on Growth

The long-term clinical course of 60 children with steroid-responsive nephrotic syndrome, observed for a minimum of 10 years from onset, was studied (mean 14.5 ± 0.5 years). Four children had only a single episode, seven children experienced only one to three relapses early in their course, and the remaining 49 patients (82%) experienced frequently relapsing steroid-dependent disease. Nearly half of these (47%) continued to relapse into their late teens and early twenties. All 20 children treated with cyclosphosphamide because of steroid-induced side effects developed complete remissions of the nephrotic syndrome. These were sustained in 70% for 9.1 ± 0.6 years, with a reduction of disease severity in the remaining 30%. In contrast, only 48% of patients treated with prednisone alone were in remission at last follow-up ( P = .06). Ten of the children treated with cyclophosphamide had the minimal change lesion prior to therapy; 90% of these had permanent remissions. Only 50% of the six children with focal glomerulosclerosis and four children with mesangial proliferation have had permanent remissions. None of the patients developed renal insufficiency. Children treated with prednisone alone were −0.93 ± 0.3 SD below the mean for height at last follow-up. Cyclophosphamide treatment was associated with an increase in height SD scores from −0.84 ± 0.4 to −0.28 ± 0.3. Children with severe growth impairment demonstrated dramatic catch-up growth when treated with cyclophosphamide with SD scores increasing from −2.29 ± 0.8 to −0.43 ± 0.6 ( P < .05). It is concluded that steroid-responsive nephrotic syndrome often follows a frequently relapsing steroid-dependent course for as long as 25 years. Cyclophosphamide favorably alters the course of this disease, particularly in patients with a minimal change lesion, and ameliorates steroid-induced growth retardation. In our experience, frequently relapsing steroid-dependent nephrotic syndrome, even when associated with lateonset focal glomerulosclerosis, did not result in renal insufficiency.