Immunosuppression in Older Kidney Transplant Recipients: A Randomized Controlled Trial (OPTIMIZE)
In the OPTIMIZE randomized trial of kidney transplant recipients aged 65 and older, a low-dose tacrolimus/everolimus/prednisolone regimen did not improve successful transplantation, kidney function, survival, or infection rates compared with standard tacrolimus/mycophenolate/prednisolone.
Background
Older recipients are less prone to rejection but more vulnerable to over-immunosuppression, infection, malignancy, and the nephrotoxicity of calcineurin inhibitors — especially with kidneys from older donors. OPTIMIZE tested whether reducing calcineurin-inhibitor exposure by combining low-dose tacrolimus with everolimus would preserve graft function better than the standard regimen.
Study design
OPTIMIZE (NCT03797196) was an open-label, multicenter randomized trial in 379 de novo recipients aged ≥65, stratified by donor type (stratum A: deceased donor >65; stratum B: living donor or deceased donor <65). Patients were randomized to low-dose tacrolimus + everolimus + prednisolone (TEP) or standard-dose tacrolimus + mycophenolate mofetil + prednisolone (TMP). The primary endpoint was 'successful transplantation' — alive with a functioning graft above a pre-defined eGFR threshold (30 in stratum A, 45 ml/min/1.73 m² in stratum B) at 2 years.
Key findings
Successful transplantation at 2 years did not differ between groups (TEP 50% vs TMP 57%; P=0.91). Patient survival (89% vs 89%; P=0.95) and graft survival (83% vs 84%; P=0.65) were also similar, with no significant differences within either stratum. Drug trough levels stayed within target throughout.
Clinical implications
Switching older recipients to a low-exposure tacrolimus/everolimus regimen offered no advantage over standard tacrolimus/mycophenolate immunosuppression on graft function, survival, or infection, so it does not support routine adoption of this CNI-sparing strategy in elderly kidney transplantation.
Category
Transplant
Source
Journal of the American Society of Nephrology (JASN)
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