New kidneys, old risks: cardiovascular challenges after transplantation

Kidney transplantation markedly improves survival and quality of life in patients with kidney failure, yet cardiovascular disease remains the leading cause of morbidity and mortality in kidney transplant recipients (KTRs). This review outlines the complex interplay of traditional, transplant-specific, and recipient- and donor-related risk factors that sustain a high cardiovascular burden post-transplantation. While kidney function restoration reduces uremic toxins and improves cardiometabolic parameters, new challenges arise from immunosuppressive therapies, persistent hypertension, post-transplant diabetes mellitus, and chronic inflammation. Common cardiovascular complications include coronary artery disease, heart failure, valvular disease, peripheral artery disease, and refractory hypertension. Risk stratification tools and guidelines often fail to account for transplant-specific variables, resulting in suboptimal management. Although some pharmacological strategies and careful antihypertensive regimens show promise, most evidence is extrapolated from non-transplant populations due to the lack of dedicated randomized controlled trials. Emerging therapies like SGLT2 inhibitors, GLP-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists hold potential but require further validation in this population. Moreover, sex disparities persist in access to transplantation and in post-transplant outcomes, with men generally experiencing higher cardiovascular risk but women potentially facing greater relative mortality. The review underscores the urgent need for transplant-specific cardiovascular research, personalized therapeutic strategies including precision medicine, and greater inclusion of women in research. Optimizing cardiovascular outcomes in KTRs will require multidisciplinary collaboration, rigorous evidence generation, and an integrated approach to risk prediction, prevention, and treatment.