Key Points

Low-dose tacrolimus, everolimus, and prednisolone did not result in a higher rate of successful transplantation in older kidney transplant recipients.

Low-dose tacrolimus, everolimus, and prednisolone did not result in better kidney function or fewer infections in older kidney transplant recipients.

Background We hypothesized that older kidney transplant recipients receiving low-dose tacrolimus, everolimus, and prednisolone (TEP) have better outcomes than patients receiving standard-dose tacrolimus, mycophenolate mofetil, and prednisolone (TMP). Methods The OPTIMIZE study was a randomized clinical trial in kidney transplant recipients age ≥65 years. Patients receiving a kidney from a deceased donor older than 65 years (stratum A) or a kidney from a deceased donor younger than 65 years or a living donor (stratum B) were included. Patients were randomized to TEP or TMP groups. Tacrolimus target trough levels in the TEP group were 5–7 ng/ml until 3 months, 2–4 ng/ml from 3 to 6 months, and 1.5–4 ng/ml from 6 months onwards. Tacrolimus target trough levels in the TMP group were 8–12, 6–10, and 5–8 ng/ml. Everolimus target trough levels were 3–6 µ g/L. The primary end point of successful transplantation was defined as being alive with a functioning graft with an eGFR above a predefined threshold at 2 years after transplantation. Predefined eGFR thresholds were 30 (stratum A) or 45 ml/min per 1.73 m 2 (stratum B). Results A total of 379 patients were randomized, of whom 198 were in stratum A (TEP 97, TMP 101) and 181 in stratum B (TEP 90, TMP 91). The median trough levels for everolimus and tacrolimus were within the target range throughout the study. There was no statistically significant difference in successful transplantation at 2 years between the groups (TEP 94 [50%], TMP 110 [57%]; difference 7% [95% confidence interval, −17 to 3] P = 0.91). Regarding the predefined secondary outcomes, patient survival (TEP 167 [89%], TMP 171 [89%]; P = 0.95) and graft survival (TEP 155 [83%], TMP 162 [84%]; P = 0.65) did not differ significantly. Within strata A and B, there were no significant differences in the end points. Conclusions Immunosuppression with low-dose tacrolimus, everolimus, and prednisolone did not result in a higher rate of successful transplantation in de novo older kidney transplant recipients compared with immunosuppression with standard-dose TMP. Clinical Trial registry name and registration number: ClinicalTrials.gov, NCT03797196.