A Five-Year Prospective, Randomized, Open-Label Study of Standard-Dose Versus Low-Dose Prolonged-Release Tacrolimus...

Area of Science:

• Nephrology
• Immunology
• Pharmacology

Background:

• Novel strategies are needed to enhance long-term outcomes for kidney transplant recipients.
• This study evaluated prolonged-release tacrolimus (TAC) at standard (STD) or low (LOW) doses, combined with ACEi/ARB or other antihypertensive therapy (OAHT).

Purpose of the Study:

• To assess 5-year treatment outcomes in Canadian kidney transplant recipients using different tacrolimus dosing and antihypertensive regimens.
• To compare patient survival, graft survival, rejection rates, and graft function between treatment groups.

Main Methods:

• A multicenter, prospective, Phase 3b trial randomized 281 adult de novo kidney transplant recipients.
• Patients received either STD or LOW dose TAC combined with ACEi/ARB or OAHT.
• Inclusion criteria included first or second transplant with at least one human leukocyte antigen mismatch.

Main Results:

• Overall patient survival was high (95.7%) and comparable across groups.
• Graft survival ranged from 89.7% to 97.1%; acute rejection and de novo donor-specific antibodies were numerically higher in the LOW+OAHT group but not statistically significant.
• Graft function, blood pressure, and proteinuria were similar, though ACEi/ARB use increased in the OAHT group over time.

Conclusions:

• Low-dose TAC with renin-angiotensin system blockade demonstrated similar 5-year outcomes compared to standard-dose TAC.
• Low-dose TAC without RAS blockade showed a non-significant trend towards increased rejections and dnDSA.
• No unexpected safety concerns were identified.