Non-immunologic mechanisms of calcineurin inhibitors explain its antiproteinuric effects in genetic glomerulopathies

Pediatr Nephrol. 2010 Jul;25(7):1197-9. doi: 10.1007/s00467-010-1469-2. Epub 2010 Mar 2.

Abstract

It has been reported (this issue Pediatric Nephrology) that cyclosporine A (CyA) therapy in combination with corticosteroids, angiotensin-converting enzyme inhibitor, and an angiotensin receptor blocker decreased proteinuria in three patients with nephrotic syndrome (NS) due to WT1 mutations. Treatment with calcineurin inhibitors were found to induce a partial remission of proteinuria in several other children with genetic forms of NS, such as mutation in the podocine and in the phospholipase C epsilon gene. CyA therapy has also been reported to be beneficial to patients with Alport syndrome. Recent data have shown that the antiproteinuric effect of CyA in these cases may be due to a non-immunologic mechanism. CyA exerts an antiproteinuria effect by preventing the degradation of the actin organizing protein synaptodpodin and by a downregulation of TRPC6. This mechanism leads to the stabilization of the actin cytoskeleton in the kidney podocytes. This beneficial effect of CyA is interesting, but long-term results regarding function and nephrotoxicity are still missing.

Publication types

  • Comment
  • Editorial

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Calcineurin Inhibitors*
  • Cyclosporine / adverse effects
  • Cyclosporine / therapeutic use*
  • Drug Therapy, Combination
  • Genes, Wilms Tumor
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Mutation
  • Nephrotic Syndrome / drug therapy*
  • Nephrotic Syndrome / genetics
  • Proteinuria / drug therapy*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Calcineurin Inhibitors
  • Glucocorticoids
  • Immunosuppressive Agents
  • Cyclosporine