Immunosuppression in Older Kidney Transplant Recipients: A Randomized Controlled Trial.

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

低剂量他克莫司、依维莫司和泼尼松并未在老年肾移植受者中改善肾功能或减少感染。

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).

我们假设接受低剂量他克莫司、依维莫司和泼尼松（TEP）的老年肾移植受者比接受标准剂量他克莫司、吗替麦考酚酯和泼尼松（TMP）的患者有更好的结果。

Methods

The OPTIMIZE study was a randomized clinical trial in kidney transplant recipients age ≥65 years.

OPTIMIZE研究是一项针对年龄≥65岁的肾移植受者的随机临床试验。

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.

纳入接受来自65岁以上逝者供体的肾脏（A层）或来自65岁以下逝者供体或活体供体的肾脏（B层）的患者。

Patients were randomized to TEP or TMP groups.

患者被随机分配到TEP组或TMP组。

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.

TEP组他克莫司目标谷值浓度为：前3个月5-7 ng/ml，3至6个月2-4 ng/ml，6个月及以后1.5-4 ng/ml。

Tacrolimus target trough levels in the TMP group were 8-12, 6-10, and 5-8 ng/ml.

TMP组他克莫司目标谷值浓度为：8-12 ng/ml，6-10 ng/ml，以及5-8 ng/ml。

Everolimus target trough levels were 3-6 µ g/L.

Everolimus的目标血药谷浓度为3-6微克/升。

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.

成功的移植的主要终点被定义为在移植后2年时，患者存活且移植器官功能良好，eGFR超过预设阈值。

Predefined eGFR thresholds were 30 (stratum A) or 45 ml/min per 1.73 m 2 (stratum B).

预设的eGFR阈值为30（A层）或45 ml/min per 1.73 m2（B层）。

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).

共有379名患者被随机分配，其中198名在A层（TEP 97，TMP 101）和181名在B层（TEP 90，TMP 91）。

The median trough levels for everolimus and tacrolimus were within the target range throughout the study.

研究期间，依维莫司和他克莫司的中位谷值水平始终处于目标范围内。

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).

在2年成功移植方面，两组之间没有统计学上的显著差异（TEP组94例[50%]，TMP组110例[57%]；差异7% [95%置信区间, -17至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.

关于预定义的次要结果，患者的生存率（TEP 167 [89%]，TMP 171 [89%]；P = 0.95）和移植物的存活率（TEP 155 [83%]，TMP 162 [84%]；P = 0.65）没有显著差异。

Within strata A and B, there were no significant differences in the end points.

在A和B层中，终点没有显著差异。

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.

在新发老年肾移植受者中，使用低剂量他克莫司、依维莫司和泼尼松的免疫抑制治疗，并没有比使用标准剂量TMP的免疫抑制治疗有更高的成功移植率。

clinical_trial_registry_name_and

ClinicalTrials.gov, NCT03797196 .

ClinicalTrials.gov, NCT03797196 .