Introduction of everolimus in kidney transplant recipients at a late posttransplant stage

Area of Science:

• Nephrology
• Transplantation Immunology
• Pharmacology

Background:

• Calcineurin inhibitors (CNIs) are standard immunosuppressants in kidney transplantation but are associated with significant nephrotoxicity.
• Everolimus (EVL), a mammalian target of rapamycin (mTOR) inhibitor, offers an alternative immunosuppressive strategy.
• Late conversion from CNIs to EVL in kidney transplant recipients is an area of ongoing research.

Purpose of the Study:

• To review current knowledge on the introduction of everolimus (EVL) with CNI elimination or minimization in late-stage kidney transplant recipients.
• To summarize findings from key clinical trials (ASCERTAIN, APOLLO) and other studies evaluating this conversion strategy.

Main Methods:

• Minireview of existing literature, including two major clinical trials and seven retrospective/nonrandomized studies.
• Analysis of estimated glomerular filtration rate (eGFR) and graft function post-conversion.
• Identification of patient subgroups and clinical indications for late conversion to EVL.

Main Results:

• The ASCERTAIN study showed no significant difference in eGFR at 24 months post-conversion, but improved GFR in recipients with higher baseline creatinine clearance (>50 mL/min) after CNI elimination.
• The APOLLO study found significantly higher adjusted eGFR in the EVL continuation group compared to CNI continuation at 12 months post-conversion.
• Other studies indicated favorable graft function with late EVL induction and CNI elimination/reduction in selected patients without adverse events.

Conclusions:

• Late conversion to everolimus (EVL) with calcineurin inhibitor (CNI) elimination or minimization can lead to favorable graft function in kidney transplant recipients.
• Indications for late conversion include chronic allograft nephropathy, CNI nephrotoxicity, CNI arteriolopathy, cancer, and viral infections (e.g., cytomegalovirus).
• Patient selection, particularly those with preserved renal function, is crucial for successful late conversion to EVL.