Background
Increasing numbers of older patients are undergoing kidney transplantation. While there is evidence for both sex- and age-related immunological variations increasing the risks of immunosuppression (IS), few centers enforce age- or sex-specific IS adjustments.

Methods
We investigated outcomes of 148 kidney transplants performed in our center between April 2009 and March 2019 in recipients aged > 60 years and compared them to outcomes in 272 younger recipients (divided into age groups 18–34, 35–49, and 50–60 years), matched for degree of human leukocyte antigen (HLA) sensitization (calculated reaction frequency, cRF), number of donor–recipient HLA mismatches, and cytomegalovirus (CMV) serostatus, all treated with the same IS protocol. Outcomes were time to (i) first episode of biopsy-proven acute rejection (BPAR), (ii) first CMV viremia within the first 6 months, (iii) incidence of any new-onset malignancy, and (iv) development of donor-specific anti-HLA antibodies (DSAs).

Results
Overall rates of BPAR were highest in the recipients under the age of 35, but with no evidence of a difference between older age groups. Conversely, the risk of CMV viremia and malignancy was significantly higher in older recipients; in the > 60-year-old group, CMV viremia HR: 2.66 (95% CI: 1.49–4.75), and malignancy HR: 7.3 (95% CI: 1.7–31.10) versus the youngest group with little evidence was confounded by comorbidity or donor factors on multivariate analysis. The risk of CMV infection was most marked in the oldest female group, while the risk of malignancy was greatest in older males. The development of DSA was equal across all age groups.

Conclusion
Our data indicate that older recipient age is associated with increased risk of CMV viremia and malignancy after transplantation, suggesting an age-associated vulnerability to IS, with the risk occurring mostly in older women and older men, respectively. These data support the need to develop age- and sex-specific​ protocol adjustments.