Impact of Immunosenescence in Older Kidney Transplant Recipients: Associated Clinical Outcomes and Possible Risk Stratification for Immunosuppression Reduction.

The number of older individuals receiving a kidney transplant as replacement therapy has significantly increased in the past decades and this increase is expected to continue. Older patients have a lower rate of acute rejection but an increased incidence of death with a functioning graft. Several factors, including an increased incidence of infections, post-transplant malignancy and cardiovascular comorbidity and mortality, contribute to this increased risk. Notwithstanding, kidney transplantation is still the best form of kidney replacement therapy in all patients with chronic kidney disease, including in older individuals. The best form of immunosuppression and the optimal dose of these medications in older recipients remains a topic of discussion. Pharmacological studies have usually excluded older patients and when included, patients were highly selected and their numbers insignificant to draw a reasonable conclusion. The reduced incidence of acute rejection in older recipients has largely been attributed to immunosenescence. Immunosenescence refers to the aging of the innate and adaptive immunity, accumulating in phenotypic and functional changes. These changes influences the response of the immune system to new challenges. In older individuals, immunosenescence is associated with increased susceptibility to infectious pathogens, a decreased response after vaccinations, increased risk of malignancies and cardiovascular morbidity and mortality. Chronic kidney disease is associated with premature immunosenescent changes, and these are independent of aging. The immunosenescent state is associated with low-grade sterile inflammation termed inflammaging. This chronic low-grade inflammation triggers a compensatory immunosuppressive state to avoid further tissue damage, leaving older individuals with chronic kidney disease in an immune-impaired state before kidney transplantation. Immunosuppression after transplantation may further enhance progression of this immunosenescent state. This review covers the role of immunosenescence in older kidney transplant recipients and it details present knowledge of the changes in chronic kidney disease and after transplantation. The impact of immunosuppression on the progression and complications of an immunosenescent state are discussed, and the future direction of a possible clinical implementation of immunosenescence to individualize/reduce immunosuppression in older recipients is laid out.