Background: The therapy of nephrotic syndrome in focal segmental glomerulosclerosis (FSGS) is still a matter of controversy.
Methods: We performed a prospective randomized study of the treatment of nephrotic syndrome due to FSGS. We compared 2 specific treatment protocols to assess the effect of treatment on proteinuria and renal function. Fifty-seven patients were randomly assigned to 2 groups: group 1 (n = 34) received steroids and cyclosporine, and group 2 (n = 23) received steroids and chlorambucil for 6 months. When treatment was refractory to chlorambucil, the patients in this group were treated with cyclosporine. Creatinine, blood urea nitrogen, proteinuria, lipids, and arterial hypertension were monitored at regular intervals.
Results: Patients showed a mean serum creatinine of 1.5 +/- 0.2 mg/dL (132.6 +/- 17.7 micromol/L) and proteinuria of 4.8 +/- 2.8 g/24 h with no differences between the groups. At the end of the chlorambucil therapy, patients in group 2 had creatinine levels of 1.8 +/- 0.6 mg/dL (159.1 +/- 53 micromol/L) and proteinuria levels of 3.4 +/- 1 g/24 h. All patients in this group were given cyclosporine. After 4 years the mean creatinine level in group 1 was 1.7 +/- 0.4 mg/dL (150.3 +/- 35.4 micromol/L) and the proteinuria level was 2.5 +/- 1 g/24 h. In group 2, the mean creatinine level was 1.9 +/- 0.6 mg/dL (168 +/- 53 micromol/L) (not significant [NS]) and the mean proteinuria level was 2.3 +/- 1.1 g/24 h (NS). Full remission occurred in 23% of the patients in group 1 (n = 8) and 17% of the patients in group 2 (n = 4; NS). Partial remission was observed in 38% of the patients in group 1 (n = 13) and 48% in group 2 (n = 11; NS). The number of patients who developed end-stage renal disease was comparable in both groups: 4 of 34 patients in group 1 after 2.5 +/- 0.8 years, and 5 of 23 patients in group 2 (NS).
Conclusion: Additional treatment with chlorambucil was found to be ineffective in FSGS. Patients responded to treatment with steroids or cyclosporine, but additional treatment with chlorambucil did not improve the patient's outcome. Future studies must focus on the long-term prognosis of these patients.