Sirolimus conversion in liver transplant recipients with renal dysfunction: a prospective, randomized, single-center...

Area of Science:

• Nephrology
• Transplantation
• Immunology

Background:

• Calcineurin inhibitors (CNI) are standard immunosuppressants post-liver transplant but can cause renal dysfunction.
• Sirolimus (SRL) is an alternative immunosuppressant with a different mechanism, potentially offering renal benefits.

Purpose of the Study:

• To evaluate the safety and efficacy of SRL in liver transplant recipients experiencing renal dysfunction.
• To compare SRL-based immunosuppression with CNI in this patient population.

Main Methods:

• A pilot randomized trial involving 40 liver transplant recipients with renal dysfunction (24-hr CrCl 40-80 mL/min).
• Patients were randomized to either CNI withdrawal with SRL initiation or continued CNI therapy (control arm).
• Renal function (24-hr CrCl) and adverse events were monitored over 12 months.

Main Results:

• The SRL arm demonstrated a significant improvement in 24-hour CrCl at 3 months (75 mL/min vs. 56 mL/min, P=0.012).
• A trend toward renal function improvement persisted in the SRL arm at 12 months (72 mL/min vs. 58 mL/min, P=0.09).
• SRL exhibited a manageable side effect profile, including hyperlipidemia, pruritus, and mouth sores. Steroid-sensitive rejection occurred in one patient per arm.

Conclusions:

• SRL-based immunosuppression appears to be a safe alternative to CNI in liver transplant recipients with renal dysfunction.
• While early renal function improvements were noted, SRL did not lead to statistically significant long-term renal function enhancement at 12 months post-transplant.