Background. Elderly kidney transplant recipients (KTRs) represent almost one third of the total kidney transplant population. These patients have a very high coronavirus disease 2019 (COVID-19)–related mortality, whereas their response to COVID-19 vaccination is impaired. Finding ways to improve the COVID-19 vaccination response in this vulnerable population is of uttermost importance. Methods. In the OPTIMIZE trial, we randomly assign elderly KTRs to an immunosuppressive regimen with standard-exposure calcineurin inhibitor (CNI), mycophenolate mofetil, and prednisolone or an adapted regimen with low dose CNI, everolimus, and prednisolone. In this substudy, we measured the humoral response after 2 (N = 32) and 3 (N = 22) COVID-19 mRNA vaccinations and the cellular response (N = 15) after 2 vaccinations. Results. . The seroconversion rates of elderly KTRs on a standard immunosuppressive regimen were only 13% and 38% after 2 and 3 vaccinations, respectively, whereas the response rates of KTRs on the everolimus regimen were significantly higher at 56% (P = 0.009) and 100% (P = 0.006). Levels of severe acute respiratory syndrome coronaVirus 2 IgG antibodies were significantly higher at both time points in the everolimus group (P = 0.004 and P < 0.001). There were no differences in cellular response after vaccination. Conclusions. An immunosuppressive regimen without mycophenolate mofetil, a lower CNI dose, and usage of everolimus is associated with a higher humoral response rate after COVID-19 vaccination in elderly KTRs after transplantation. This encouraging finding should be investigated in larger cohorts, including transplant recipients of all ages.

Background In 2019, more than 30 % of all newly transplanted kidney transplant recipients in The Netherlands were above 65 years of age. Elderly patients are less prone to rejection, and death censored graft loss is less frequent compared to younger recipients. Elderly recipients do have increased rates of malignancy and infection-related mortality. Poor kidney transplant function in elderly recipients may be related to both pre-existing (i.e. donor-derived) kidney damage and increased susceptibility to nephrotoxicity of calcineurin inhibitors (CNIs) in kidneys from older donors. Hence, it is pivotal to shift the focus from prevention of rejection to preservation of graft function and prevention of over-immunosuppression in the elderly. The OPTIMIZE study will test the hypothesis that reduced CNI exposure in combination with everolimus will lead to better kidney transplant function, a reduced incidence of complications and improved health-related quality of life for kidney transplant recipients aged 65 years and older, compared to standard immunosuppression. Methods This open label, randomized, multicenter clinical trial will include 374 elderly kidney transplant recipients (≥ 65 years) and consists of two strata. Stratum A includes elderly recipients of a kidney from an elderly deceased donor and stratum B includes elderly recipients of a kidney from a living donor or from a deceased donor < 65 years. In each stratum, subjects will be randomized to a standard, tacrolimus-based immunosuppressive regimen with mycophenolate mofetil and glucocorticoids or an adapted immunosuppressive regimen with reduced CNI exposure in combination with everolimus and glucocorticoids. The primary endpoint is ‘successful transplantation’, defined as survival with a functioning graft and an eGFR ≥ 30 ml/min per 1.73 m2 in stratum A and ≥ 45 ml/min per 1.73 m2 in stratum B, after 2 years, respectively. Conclusions The OPTIMIZE study will help to determine the optimal immunosuppressive regimen after kidney transplantation for elderly patients and the cost-effectiveness of this regimen. It will also provide deeper insight into immunosenescence and both subjective and objective outcomes after kidney transplantation in elderly recipients. Trial registration ClinicalTrials.gov: NCT03797196, registered January 9th, 2019. EudraCT: 2018-003194-10, registered March 19th, 2019.

Summary Increasing numbers of elderly (≥65 years) patients are listed for kidney transplantation. This study compares the survival outcome between living (LDK), regularly allocated (ETKAS), and Eurotransplant Senior Program (ESP) donor kidneys in elderly recipients. This is a single‐center retrospective cohort study of elderly kidney transplant recipients transplanted between 2005 and 2017. Primary outcome measures were nondeath‐censored graft, death‐censored graft, and patient survival. In total, 348 patients were transplanted, 109 recipients (31.3%) received an LDK, 100 (28.7%) an ETKAS, and 139 (40%) an ESP kidney. 62.5% were male, and median age was 68 years. LDK recipients had significantly better 5‐year nondeath‐censored graft survival compared with ETKAS and ESP (resp. 71.0% vs. 66.1% vs. 55.6%, P = 0.047). Death‐censored graft survival after 1 year was significantly better in LDK recipients (99.1%) (ETKAS 90.8%; ESP 87.7%, P < 0.001). After 5 years, the difference remained significant (P < 0.001) with little additional graft loss (97.7% vs. 88.1% vs. 85.6). There was no significant difference in patient survival after 5 years (71.7% vs. 67.4% vs 61.9%, P = 0.480). In elderly recipients, the patient survival benefits of an LDK are limited, but there is decreased death‐censored graft loss for LDK recipients. Nevertheless, graft survival in ETKAS and ESP remains satisfactory.