We prospectively examined the effect of treatment with intravenous
cyclophosphamide in patients with
steroid-resistant nephrotic syndrome. Twenty-four patients (
minimal change disease in 11,
focal segmental glomerulosclerosis in 9, and mesangioproliferative
glomerulonephritis in 4), who did not show remission of
proteinuria despite treatment with 8 weeks of oral
prednisolone and six intravenous pulses of
dexamethasone, were studied.
Cyclophosphamide was administered intravenously, at a dose of 750 mg/m(2) once a month for 6 months;
therapy with alternate-day
prednisolone was continued. The mean (SD) age at treatment was 7.8 (4.0) years; 18 patients had initial resistance and 6 had late resistance. At the end of 6 months treatment, 7 (29.2%) patients each had complete remission (absent
proteinuria, normal
serum albumin) and partial remission (1-2+
proteinuria, normal
serum albumin). Ten (41.6%) patients showed no response to
therapy. The mean time to complete or partial remission, after initiation of treatment with
cyclophosphamide, was 2.4+/-1.7 months and 2.7+/-1.8 months, respectively. Most responders (85.8% complete and 57.2% partial responders) achieved remission by the third dose of pulse
cyclophosphamide. More patients with late resistance (50%) compared with initial resistance (22.2%) achieved complete remission. Partial remission was transient and lasted for a mean duration of 6.4+/-3.5 months. Serious
infections were observed during
therapy in 5 patients. On long-term follow-up, 5 (20.8%) patients were in remission, while nephrotic-range
proteinuria or
end-stage renal disease was seen in 17 (70.8%). Findings from the present study suggest that
therapy with intravenous
cyclophosphamide has limited efficacy in inducing sustained remission in patients with initial
corticosteroid resistance. Sustained remission is likely to occur in a significant proportion of patients with late resistance and those with absence of significant tubulointerstitial changes on renal histology.