Protocol conversion from a calcineurin inhibitor based therapy to sirolimus.

Area of Science:

• Nephrology
• Immunosuppression
• Transplantation

Background:

• Calcineurin inhibitors (CNI) are standard immunosuppressants post-kidney transplant.
• CNI use is associated with nephrotoxicity and other adverse effects.
• Sirolimus (SRL) is an alternative immunosuppressant with a different side effect profile.

Purpose of the Study:

• To evaluate the safety and efficacy of converting stable kidney transplant recipients from CNI to SRL.
• To assess the impact of SRL conversion on renal function, specifically glomerular filtration rate (GFR).
• To compare the incidence of malignancies in patients converted to SRL versus those remaining on CNI.

Main Methods:

• Review of small, late-conversion studies and larger trials like CONVERT, spare the nephron, and CONCEPT.
• Analysis of GFR measurements at 1 year post-conversion.
• Comparison of malignancy rates between SRL and CNI groups.

Main Results:

• Small studies indicated a significant GFR increase after CNI to SRL conversion.
• The larger CONVERT study did not detect a significant GFR increase but showed a lower malignancy rate in the SRL group.
• The spare the nephron and CONCEPT trials reported higher GFR in SRL-converted patients at 1 year.

Conclusions:

• Conversion from CNI to SRL appears safe for stable renal transplant recipients.
• The impact on GFR may vary depending on study size and design.
• SRL conversion may be associated with a reduced risk of malignancies.