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

IF 3.4 3区 医学 Q2 GERIATRICS & GERONTOLOGY Drugs & Aging Pub Date : 2024-03-01 Epub Date: 2024-02-22 DOI:10.1007/s40266-024-01100-5
Borefore P Jallah, Dirk R J Kuypers
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Abstract

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.

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免疫衰老对老年肾移植受者的影响:相关临床结果和减少免疫抑制的可能风险分层。
在过去几十年中,接受肾移植替代治疗的老年患者人数大幅增加,预计这种增长还将继续。老年患者的急性排斥反应发生率较低,但在移植肾功能正常的情况下,其死亡发生率却有所增加。感染、移植后恶性肿瘤、心血管合并症和死亡率的增加等几个因素导致了这种风险的增加。尽管如此,肾移植仍然是所有慢性肾病患者(包括老年人)的最佳肾脏替代疗法。免疫抑制的最佳形式以及这些药物对老年受者的最佳剂量仍是一个讨论话题。药理学研究通常不包括老年患者,即使包括了老年患者,也是经过严格筛选的,其数量微不足道,无法得出合理的结论。老年受者急性排斥反应发生率降低主要归因于免疫衰老。免疫衰老指的是先天性免疫和适应性免疫的老化,表型和功能变化的累积。这些变化会影响免疫系统对新挑战的反应。在老年人中,免疫衰老与对感染性病原体的易感性增加、接种疫苗后反应减弱、恶性肿瘤风险增加以及心血管疾病的发病率和死亡率增加有关。慢性肾病与免疫衰老的过早变化有关,而这些变化与衰老无关。免疫增强状态与低级无菌炎症有关,称为炎症aging。这种慢性低度炎症会引发一种代偿性免疫抑制状态,以避免进一步的组织损伤,从而使患有慢性肾病的老年人在肾移植前处于免疫受损状态。移植后的免疫抑制可能会进一步加剧这种免疫增强状态。这篇综述涵盖了免疫衰老在老年肾移植受者中的作用,并详细介绍了有关慢性肾病和移植后免疫衰老变化的现有知识。文章讨论了免疫抑制对免疫衰老状态的进展和并发症的影响,并阐述了在临床上实施免疫衰老以个性化/减少对老年受者的免疫抑制的未来方向。
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来源期刊
Drugs & Aging
Drugs & Aging 医学-老年医学
CiteScore
5.50
自引率
7.10%
发文量
68
审稿时长
6-12 weeks
期刊介绍: Drugs & Aging delivers essential information on the most important aspects of drug therapy to professionals involved in the care of the elderly. The journal addresses in a timely way the major issues relating to drug therapy in older adults including: the management of specific diseases, particularly those associated with aging, age-related physiological changes impacting drug therapy, drug utilization and prescribing in the elderly, polypharmacy and drug interactions.
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