Cyclosporine versus everolimus: effects on the glomerulus

Area of Science:

• Nephrology
• Immunology
• Transplantation

Background:

• Mammalian target of rapamycin (mTOR) inhibitors are associated with proteinuria.
• Understanding the impact of mTOR inhibitors on renal transplant recipients (RTR) is crucial.

Purpose of the Study:

• To investigate proteinuria development in RTR treated with everolimus versus calcineurin inhibitors.
• To correlate proteinuria with histopathological glomerular findings in protocol biopsies.

Main Methods:

• Single-center study nested in a multicenter randomized controlled trial.
• Compared RTR on prednisolone/everolimus (P/EVL) with those on prednisolone/cyclosporine A (P/CsA).
• Assessed estimated glomerular filtration rate (eGFR), proteinuria, and renal biopsy data (light and electron microscopy) at two years post-transplantation.

Main Results:

• No significant difference in renal function (eGFR) between P/EVL and P/CsA groups at two years.
• Slightly increased proteinuria observed in the P/EVL group compared to the P/CsA group (0.29 vs. 0.14 g/24 h, p = 0.06).
• No differences in light or electron microscopy findings, including podocyte effacement or glomerular basement membrane thickness.

Conclusions:

• Long-term treatment with everolimus did not adversely affect glomerular basement membrane or podocytes in RTR.
• Everolimus may lead to a slight increase in proteinuria without significant structural glomerular damage.