Immunosuppressive treatment for focal segmental glomerulosclerosis in adults.

BACKGROUND: Corticosteroids remain the mainstay of treatment in idiopathic nephrotic syndrome, including focal and segmental glomerulosclerosis (FSGS). However, only about 20% of patients with FSGS experience a partial or complete remission of nephrotic syndrome despite treatment.
OBJECTIVES: To assess the effects of different immunomodulatory and immunosuppressive regimes in adults with FSGS. SEARCH STRATEGY: We searched MEDLINE, EMBASE and CENTRAL and handsearched congress reports of the American Society of Nephrology and the European Dialysis and Transplantation Association. Date of search: 31 January 2007. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs which examined the effects of different doses, dose strategies and duration of treatment of steroids, alkylating agents, cyclosporin A and antimetabolites in the treatment of FSGS in adults, where included. DATA COLLECTION AND ANALYSIS: At least two authors independently assessed abstracts and/or full text articles to determine which studies satisfied the inclusion criteria. Information was entered onto a separate data sheet for each identified study. Data relevant to outcomes (complete or partial remission of nephrotic syndrome, doubling of serum creatinine, adverse effects) from identified studies were included. Results were expressed as risk ratios (RR) with 95% confidence intervals (CI). MAIN
RESULTS: Four studies (108 participants) were included. Three studies investigated cyclosporin A (CSA) with or without prednisone versus prednisone or no treatment and one compared chlorambucil plus prednisone versus no treatment. Outcome data was only available for complete or partial remission and doubling of serum creatinine. There was a significant increase in the number of participants who obtained complete or partial remission with CSA plus low dose prednisone versus prednisone alone (one study, 49 participants: RR 8.85, 95% CI 1.22 to 63.92). Pooled analyses were not performed due to the heterogeneity of the data. AUTHORS'
CONCLUSIONS: Adult patients treated with CSA at an initial dose of 3.5-5 mg/kg/d in two divided doses perhaps in combination with oral prednisolone 0.15 mg/kg/d are more likely to achieve a partial remission of the nephrotic syndrome compared with symptomatic treatment or prednisolone alone. However, there is a probability of deterioration of kidney function due to the nephrotoxic effect of CSA in the long term. For CSA, a larger controlled trial with longer follow-up should be performed to prove the benefit of this regimen not only on proteinuria but also on the preservation of kidney function. Present available data do not support the general use of alkylating substances for the treatment of FSGS in adults.