A prolonged course with
corticosteroids represents the first therapeutic approach for nephrotic patients with
focal segmental glomerulosclerosis (FSGS). In patients with
contraindications to
steroids or in those who do not respond to
steroids or
cyclosporine,
cytotoxic agents,
mycophenolate mofetil (MMF),
plasmapheresis, and
low-density lipoprotein (
LDL)
apheresis have been tried as alternative treatments. A short-term treatment with
cytotoxic agents often is ineffective in
steroid-resistant patients However, an aggressive and prolonged treatment with
cytotoxic agents combined with
corticosteroids proved to be effective in more than half of
steroid-resistant children. In adults, the response to
cytotoxic agents was good in
steroid-responsive patients, but was poor in
steroid-resistant patients. Better results were observed when cytotoxic
therapy was prolonged for several months. The problem with these drugs is that long-term immunosuppression may be complicated by severe side effects including a major risk for
cancer. Uncontrolled studies reported that MMF can induce some reduction of
proteinuria, but complete remission of
proteinuria was rare and no data on long-term follow-up evaluation with this
drug are available. Good results have been reported with
plasmapheresis, immunoadsorption, and lipopheresis. However, all the reports were uncontrolled, small sized, and with short-term follow-up evaluation. In conclusion, there are several therapeutic options for patients who respond to
steroids and have further relapses of
nephrotic syndrome, but how to treat
steroid-resistant patients is still a matter of debate. Nevertheless, a 6-month trial with
cytotoxic agents or MMF can be offered to
steroid-resistant patients to identify the few patients who respond to these agents. The preliminary results with
plasmapheresis or lipopheresis are promising but further studies are needed to assess the role of these treatments.