title: A Rationale for Age-Adapted Immunosuppression in Organ Transplantation.
abstract: Demographic changes are associated with a steady increase of older patients with end-stage organ failure in need for transplantation. As a result, the majority of transplant recipients are currently older than 50 years, and organs from elderly donors are more frequently used. Nevertheless, the benefit of transplantation in older patients is well recognized, whereas the most frequent causes of death among older recipients are potentially linked to side effects of their immunosuppressants.Immunosenescence is a physiological part of aging linked to higher rates of diabetes, bacterial infections, and malignancies representing the major causes of death in older patients. These age-related changes impact older transplant candidates and may have significant implications for an age-adapted immunosuppression. For instance, immunosenescence is linked to lower rates of acute rejections in older recipients, whereas the engraftment of older organs has been associated with higher rejection rates. Moreover, new-onset diabetes mellitus after transplantation is more frequent in the elderly, potentially related to corticosteroids, calcineurin inhibitors, and mechanistic target of rapamycin inhibitors.This review presents current knowledge for an age-adapted immunosuppression based on both, experimental and clinical studies in and beyond transplantation. Recommendations of maintenance and induction therapy may help to improve graft function and to design future clinical trials in the elderly.
authors.affiliation: 1 Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. 2 Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany. 3 Division of Transplant Surgery and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Felix
authors.initials: F
authors.lastname: Krenzien
authors.forename: Abdallah
authors.initials: A
authors.lastname: ElKhal
authors.forename: Markus
authors.initials: M
authors.lastname: Quante
authors.forename: Hector
authors.initials: H
authors.lastname: Rodriguez Cetina Biefer
authors.forename: Uehara
authors.initials: U
authors.lastname: Hirofumi
authors.forename: Steven
authors.initials: S
authors.lastname: Gabardi
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Tullius
mesh_terms: D000367:Age Factors; D000375:Aging / Q000276:immunology*; D000818:Animals; D015897:Comorbidity; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D016867:Immunocompromised Host; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects / Q000379:methods*; D018579:Patient Selection; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents