Kidney transplantation remains the treatment of choice for end-stage renal disease, even in older adults. However, balancing immunosuppression against the risk of drug-related toxicity to prevent graft rejection remains a challenge in this population. A hypothesis has been raised that with reduced immune responsiveness accompanying aging, older recipients may benefit from lower immunosuppressive exposure. The OPTIMIZE study tested whether a regimen combining low-dose tacrolimus with everolimus and prednisolone might improve long-term graft and patient outcomes compared with standard-dose tacrolimus, mycophenolate mofetil, and prednisolone.
The OPTIMIZE trial was a multicenter, randomized, controlled clinical study that enrolled kidney transplant recipients who were aged 65 years or older. Of 379 patients, 198 were randomized to stratum A (recipients of kidneys from deceased donors older than 65 years) and 181 to stratum B (recipients of kidneys from younger deceased or living donors). Participants were assigned either to the TEP group (low-dose tacrolimus, everolimus, prednisolone) or to the TMP group (standard-dose tacrolimus, mycophenolate mofetil, prednisolone).
In the TEP group, tacrolimus trough levels were maintained at 5–7 ng/mL until 3 months, 2–4 ng/mL from 3–6 months, and 1.5–4 ng/mL thereafter. The respective trough levels for these time frames in the TMP group were 8–12 ng/mL, 6–10 ng/mL, and 5–8 ng/mL. Successful transplantation was defined as being alive with a functioning graft and an eGFR above 30 mL/min/1.73m² (for stratum A) or 45 mL/min/1.73m² (for stratum B) at 2 years post-transplantation.
Results
No statistically significant difference was found between the 2 arms in successful transplantation rates.
By 2 years, successful transplantation was achieved by 50% (n=94) of patients in the TEP group and 57% (n=110) in the TMP group (difference 7%; 95% CI, −17 to 3; P=0.91).
In fact, patient survival was almost exactly comparable, with 89% (n=167) in the TEP group versus 89% (n=171) in the TMP group (P=0.95).
Graft survival was similarly not significantly different, seen in 83% (n=155) for the TEP group and 84% (n=162) for the TMP group (P=0.65).
In addition, there were no significant differences observed in any major endpoint in stratified analysis based on donor age: strata A and B.
The OPTIMIZE trial concluded that immunosuppression with low-dose tacrolimus, everolimus, and prednisolone did not result in superior success of transplantation, kidney function, or survival compared to a standard-dose tacrolimus, mycophenolate mofetil, and prednisolone regimen. Researchers emphasize that standard immunosuppressive regimens remain appropriate for elderly kidney transplant recipients, since reduced tacrolimus dosing confers no additional clinical benefit.
Reference:
Sanders, Jan-Stephan F.1; de Boer, Silke E.1; Jonker, Jip1; Bemelman, Frederike J.2; Betjes, Michiel G.H.3; de Vries, Aiko P.J.4; Hilbrands, Luuk5; Hilhorst, Marc2; Kuypers, Dirk R.J.6; Vart, Priya1; van Zuilen, Arjan D.7; Hesselink, Dennis A.3; Berger, Stefan P.1. Immunosuppression in Older Kidney Transplant Recipients: A Randomized Controlled Trial. Journal of the American Society of Nephrology ():10.1681/ASN.0000000924, November 7, 2025. | DOI: 10.1681/ASN.0000000924
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