Treatment of focal segmental glomerulosclerosis.
Focal segmental glomerulosclerosis (FSGS) is not a disease, but a lesion affecting the podocyte. Secondary FSGS may be due to a host of various factors, and patients are rarely nephrotic, requiring symptomatic treatment only. The best prognostic feature of nephrotic FSGS is its response to corticosteroids. Some forms are most likely of immunological origin, relapse in a renal transplant and justify immunosuppressive treatment. In a growing number of cases, genetic profiling of molecules that contribute to the podocyte slit diaphragm permselectivity to albumin has identified defects that do not represent indications for immunosuppression. In the other forms, corticosteroids and cyclosporin A (CsA) remain the mainstay of treatment, with better efficacy when CsA is associated with steroids. The renal tolerability of CsA is reasonably good when the dosage is low. CsA dependency is not constant. Alkylating agents are reluctantly indicated in steroid-sensitive forms, which are rare. They are mostly ineffective in steroid-resistant forms. Tacrolimus seems a promising therapy with low toxicity, but it is usual for dependency on the drug to occur. Sirolimus seems to be ineffective. Azathioprine is not considered indicated, despite rare reports with favourable results, which would deserve further controlled trials. Recent publications indicate that mycophenolate mofetil might usefully find a place in the treatment. Plasmapheresis is of no avail outside the special case of relapse in a transplanted kidney. Immunoabsorption of the elusive substance that causes the nephrotic syndrome and its relapse on a transplant has not led to practical treatment options.
Meyrier
Alain
A
Hôpital Georges Pompidou, Université Paris-Descartes, 20 rue Leblanc, 75015 Paris, France. alain.meyrier@brs.ap-hop-paris.fr
D000477:Alkylating Agents / Q000627:therapeutic use*; D000963:Antimetabolites / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D000075202:Contraindications; D003520:Cyclophosphamide / Q000627:therapeutic use; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D004351:Drug Resistance; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D020104:Immunophilins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D009404:Nephrotic Syndrome / Q000209:etiology; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use
D000477:Alkylating Agents; D000963:Antimetabolites; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003520:Cyclophosphamide; D020104:Immunophilins; D009173:Mycophenolic Acid; D001379:Azathioprine; D016559:Tacrolimus