Conversion to sirolimus in solid organ transplantation: a single-center experience

Area of Science:

• Nephrology
• Transplantation Immunology
• Pharmacology

Background:

• Calcineurin inhibitors (CNIs) are associated with adverse events like nephrotoxicity and diabetes, potentially impacting long-term graft survival.
• This study focuses on converting kidney, kidney-pancreas, pancreas, and liver transplant recipients experiencing CNI-induced nephrotoxicity, hemolytic uremic syndrome (HUS), chronic allograft nephropathy, or glucose intolerance.

Purpose of the Study:

• To evaluate the efficacy of converting patients from calcineurin inhibitors to a sirolimus-based immunosuppressive regimen.
• To assess the impact of this conversion on graft function and adverse events in solid organ transplant recipients.

Main Methods:

• Abrupt discontinuation of calcineurin inhibitors followed by initiation of sirolimus (8-12 mg loading dose).
• Sirolimus trough levels were maintained at 12-16 ng/mL.
• Daclizumab was administered to kidney-pancreas and pancreas recipients on days 0 and 14 post-conversion.

Main Results:

• Complete resolution of HUS in 12 of 12 patients, with a significant improvement in serum creatinine (3.3 to 1.8 mg/dL).
• Sirolimus conversion improved serum creatinine in patients with nephrotoxicity, HUS, and chronic allograft nephropathy (2.9 to 2.2 mg/dL).
• Glucose intolerance resolved in 58% of patients; 2 patients experienced rejection due to noncompliance. Lipid levels increased, while platelet counts remained stable.

Conclusions:

• A calcineurin inhibitor-free immunosuppressive regimen using sirolimus, mycophenolate mofetil, and steroids can preserve graft function.
• This strategy is beneficial for patients requiring calcineurin inhibitor discontinuation due to adverse events.
• Sirolimus-based immunosuppression offers a viable alternative for managing transplant recipients with specific clinical indications.