Editorial: Silver linings: navigating the challenges and opportunities of organ transplantation in an Ageing population
Year: 2026
Type: editorial
Abstract: The ageing of the general population is a consequence of medical progress and improved standards of living. Older "chronologic" age arguably does not necessarily lead to older "biological" age. In parallel, progress in transplant medicine and surgery has allowed to consider transplantation for an older population of patients with endstage organ failure, who would have been considered too frail in the past. But how do such patients really benefit from organ transplantation ? how to balance the ethics of organ donor shortage versus a naturally lower life expectancy of patients who are however equally entitled to best possible healthcare ?In an registry review from Germany, Schröter et al. have analyzed the outcomes of kidney transplantation, and in particular infection burden, graft function, and mortality, in a cohort of 572 patients stratified for age (1). In older recipients (>60 years old), the unadjusted 5-year rates of graft failure, mortality, and infections were significantly higher-both overall and for specific types, including pneumonia, urinary tract infections, invasive opportunistic infections, and multidrug-resistant infections. However, after adjustment for confounding variables, only 5-year mortality was, unsurprisingly, found to be higher in the older age group. Older patients were more likely to have Pseudomonas aeruginosa, more severe herpesvirus infections, and higher infection-related morbidity. This study demonstrate that age-alone is not a predictor of adverse events, but that post-transplant care in older recipients should focus on early infection control and pathogen-targeted surveillance.Infection after kidney transplantation in older ecipients is the focus of a paper by Fayos et al. in a prospective single-center cohort study of 712 patients over 8 years (2). The occurrence of overall, bacterial and opportunistic post-transplant infection was studied with stratification by 10-year levels, with the older group aged >80 years. In unadjusted analyses, each 10-year-increase was associated with an increase in the incidence of overall, bacterial and opportunistic infection. After multivariate adjustment for confounders, this association remained significant for overall and bacterial infection, the highest risk being at >70 years. As a potential explanation for this observation, the authors show interesting data of decreasing circulating T-cell counts (CD3, CD4, CD8) with each 10-year age increase. This article has a slightly dicerent conclusion than the German study by Schröter et al (1) with a conclusion that the risk of infection after kidney transplantation increases with age after 60 years. These dicerences may be explained in part by the higher age of their cohort and dicerences in follow-up.In a retrospective single-center study by Winkler et al. performed on >1700 kidney transplant recipients, causes of graft loss were analyzed and stratified by era and by recipient age (3). Unsurprisingly, the proportion of death-with-function increased stepwise with age. The reverse was observed for rejection as a cause of graft failure, with its incidence markedly decreasing with increasing age. Similar observations were made in the three time periods studied between 1995 and 2022.The ageing of the general population also acects organ donor age, which has been increasing in the past decades. Upper age limits for considering a donor as "marginal" or "expanded criteria donor" have had to be pushed upwards to face this new reality. An age-adjusted donor score has been proposed to facilitate selection of organ donors aged >65 years (4). Intriguing reports have shown that chronic antibody-mediated rejection was more prominent with older kidney donors (5). In the context of living donation, we already know that kidney transplant from an older donor is preferable to waiting for a younger donor with brain death (DBD) (6). But how is this functioning in practice for deceased donation ? How is risk aversion still present when ocered an organ from an old patient ? What are the age limits ? Are there mitigation strategies ? An article by Chotkan et al. has looked at the causes for declining donor ocers in the Netherlands and analyzed all ocers made by the national organ allocation system between 2018-2023 (7). In this 5-year period alone, the donor age has progressively increased from a mean age of 54 years to 57 years, the proportion of donors >65 years reaching 36%. In parallel, the proportion of donors declined for transplantation has increased from 23% to 30%. In multivariate analysis, older age (>65 years) was one of the main factors independently associated with rejection of a donor ocer, the others being DCD donation, and co-morbidities (hypertension and diabetes). This demonstrates, that older donors are still considered "marginal" independently of other potential medical considerations and without necessarily solid evidence for poorer quality.The Eurotransplant Senior Program (ESP) was established to enhance kidney allocation from older donors, in order to address the shortage of organs for kidney transplantation. The ESP allocates kidneys from deceased donors aged ≥65 years to older recipients ≥65 years who left the general kidney waiting list for the benefit of significantly shorter waiting times. It is mainly based on minimizing cold ischemia time (CIT) by allocating organs locally. An opinion piece by Giorgakis et al. argues that the application of an age match scheme in the US allocation rules, quite similar to the ESP (8). They convicingly suggest that such realignments may reduce organ discard rates, enhance long-term graft utility, alleviate decision-making burdens on patients, and decrease the need for re-transplants on younger patients.An article by Langer et al. has taken a look at the outcomes of patients transplanted under this scheme (9). One-year and 5-year graft and patient survival were excellent, and notably superior to survival on dialysis. Delayed graft function (DGF) was high at almost 30%, but very much related to long CIT. HLA mismatch was not related to graft outcomes. The interesting feature of the article is the histology data of the biopsy taken immediately after reperfusion. The degree of glomerulosclerosis and interstitial fibrosis and tubular atrophy (IFTA) were associated with graft failure and arteriolosclerosis (arteriolar hyalinosis) correlated with a higher risk for primary non-function. This study demonstrates the validity of the ESP, demonstrates the importance of maintaining short CIT in this donor population and suggests that pre-transplant biopsy could provide useful selection criteria for donor acceptance.The impact of CIT in the ESP has been further studied by Matuschik et al. (10). As mentionned above, within the ESP, kidneys are prefrentially allocated locally in order to minimize CIT. In this article, the authors have assessed the impact of CIT on DGF and long-term outcomes in consecutively transplanted ESP recipients from the same donor. DGF incidence was similar for first and second recipients. CIT >12 h significantly increased DGF risk. Death-censored allograft survival was unacected, but CIT >12 h tripled mortality risk. Consecutive transplantation does not disadvantage the second recipient if CIT remains <12 h. CIT >12 h independently predicts DGF and higher mortality, emphasizing the need to minimize ischemia time when older donors are utilized.Is the detrimental impact of ischemia-reperfusion injury only caused by CIT ? In this article by Süsal et al., the authors have looked at the impact of ischemic events occuring in the donor before declaration of brain death. More specifically, they have studied the impact of cardiopulmonary resuscitation (CPR) in a cohort of ≥65-year-old kidney donors (11). In this tri-center study from Germany,all kidney from ≥65-year-old donors (2006-2023) were retrospectively analyzed and outcomes of KTs from donors with and without a history of CPR were compared. There were no dicerences in DGF occurrence or 1-year and 5-year kidney graft function between CPR and non-CPR donors. Five-year graft and patient survival were similar. Although some extent of selection bias is unavoidable in this retrospectove study, data indicate that ≥65-yearold DBD donors with a history of CPR are potentially suitable for kidney transplantation without negative impact on outcomes.call "very old" donors (12). More specifically, they have studied the risk factors for longterm graft loss or DGF after transplantation of kidney from DBD donors > 70 years. In a French national cohort of >1000 recipients, donor hypertension, CIT and HLA mismatches were significant risk factors for graft loss. With regard to DGF, donor serum creatinine, warm and cold ischemia times were deleterious, while hypothermic perfusion machine was protective. These findings emphasize the paucity of modifiable variables associated with long-term outcomes in older donors and the need for peritransplant preservation strategies.The study from Maanaoui et al. suggests that machine perfusion may be routinely necessary (12). What about the liver or thoracic organs ? Indeed, the routine use of machine perfusion for thoracic organs procured from older donors has been advocated in ESOT recommendations (13).In a national survey, Ibrahim et al. have surveyed among all 39 liver and kidney transplant centers in Germany, with a 56% response rate (14). Liver transplantation programs utilize both hypothermic and normothermic perfusion, whereas perfusion strategies in kidney transplantation remain largely limited to hypothermic techniques. Most liver centers use machine perfusion selectively for marginal grafts and have reported an average 10% increase in organ utilization rates attributed to machine perfusion. In Germany, where DCD organ donation is not legally permitted (15), marginal donors are essentially represented by older age.Giorgakis et al. have conducted a national cohort study using registry data from the United States and looking at activities and outcomes of the use of various machine perfusion techniques in liver transplantation according to donor age (16). The cohort showed accelerated growth in DCD liver transplantation after FDA approval of machine perfusion. Donors ≥60 rose 7.8-fold, including donors ≥70. By 2025, DCD livers accounted for 43%, with 61% from donors ≥50. Normothermic regional perfusion (NRP) Hypothermic machine perfusion (HMP) and sequential NRP-HMP increased significantly. This led to a decrease in the average time on the waiting list without impacting graft and patient survival. This study shows that the utilizaton of machine perfusion techniques is associated with an increased utilization of older DCD liver transplants and an acceptable early graft survival.Senotherapeutics: a look into the (near) future Chronological age captures organ quality only imperfectly, and markers that reflect biological rather than calendar ageing are therefore increasingly sought as the donor pool grows older. In a review closing this special issue, Buch et al. have examined the contribution of cellular senescence, a hallmark of ageing, to the successive stages of the transplant process, from procurement and preservation to graft function after implantation (17). They argue that senescence burden could serve both as an objective metric of organ quality and as a therapeutic target in its own right. Of particular interest is the proposed combination of senotherapeutic agents with ex vivo machine perfusion, which would allow senescence burden to be quantified and targeted interventions to be delivered to the graft before implantation, with the aim of reconditioning marginal organs rather than discarding them. These strategies remain largely experimental, but they illustrate how the assessment of donor organs may in the future move beyond age alone.Taken together, the contributions to this special issue draw a more nuanced picture than the one that has long guided practice. Outcomes are driven by a variety of modifiable (infection burden, cold ischemia time, donor comorbidity and preservation strategy) and unmodifiable risk factors. Age is a powerful risk marker, but unfortunately it is not modifiable one. Older recipients derive a survival benefit from transplantation that dialysis cannot match; organs from older donors perform considerably better than their discard rates would suggest; and age-aligned allocation, short ischemia times, pre-implantation histology and machine perfusion all ocer concrete ways of converting a demographic constraint into additional transplants. The task for the coming years will be to replace chronological age with measures of biological age that are robust enough to guide acceptance decisions at the bedside. Should we succeed, the ageing of our donor and recipient populations may prove less of a threat than an opportunity, which is the silver lining we had in mind when assembling this collection.
Source: Transplant International
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,051
OpenAlex ID: W7223270655