Other immunosuppressive agents for focal segmental glomerulosclerosis

Semin Nephrol. 2003 Mar;23(2):242-8. doi: 10.1053/snep.2003.50023.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Disease Progression
  • Dose-Response Relationship, Drug
  • Glomerulosclerosis, Focal Segmental / drug therapy*
  • Glomerulosclerosis, Focal Segmental / metabolism
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Failure, Chronic / drug therapy
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / metabolism
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use*
  • Nephrotic Syndrome / drug therapy
  • Nephrotic Syndrome / etiology
  • Nephrotic Syndrome / metabolism
  • Proteins / drug effects
  • Proteins / metabolism
  • Proteinuria / chemically induced

Substances

  • Immunosuppressive Agents
  • Proteins
  • Mycophenolic Acid