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mToR inhibitors-induced proteinuria: mechanisms, significance, and management

Emmanuel Letavernier1, Christophe Legendre

  • 1Transplantation Unit, Hôpital Necker, 75743 Paris, France. emmanuel.letavernier@tnn.ap-hop-paris.fr

Transplantation Reviews (Orlando, Fla.)
|July 18, 2008
PubMed

Insights

Mammalian target of rapamycin (mToR) inhibitors, like sirolimus, can cause significant proteinuria in kidney transplant patients. This review explores the mechanisms and implications of mToR inhibitor-induced proteinuria.

Area of Science:

  • Nephrology
  • Transplantation Immunology
  • Pharmacology

Background:

  • Massive urinary protein excretion is a known issue in renal transplant recipients converting from calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors, particularly sirolimus.
  • Proteinuria is a significant predictor of poor outcomes in kidney transplantation, prompting extensive research into its causes.

Purpose of the Study:

  • To investigate the causal link between sirolimus therapy and proteinuria, distinguishing it from calcineurin inhibitor withdrawal.
  • To explore the potential mechanisms and clinical significance of proteinuria induced by mToR inhibitors.

Main Methods:

  • Review of existing literature on proteinuria in renal transplant recipients treated with mToR inhibitors.
  • Analysis of cases involving sirolimus therapy in islet transplantation and de novo treatment.

Main Results:

  • High-level proteinuria has been observed during sirolimus therapy in various contexts, suggesting a direct effect of the drug.
  • Podocyte injury and focal segmental glomerulosclerosis have been associated with mToR inhibition, though underlying pathways require further elucidation.

Conclusions:

  • mToR inhibitor-induced proteinuria is a distinct clinical event, not solely a consequence of calcineurin inhibitor withdrawal.
  • Understanding the mechanisms of mToR blockade-induced proteinuria is crucial for managing transplant outcomes.

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