Living donor kidney transplantation is the optimal treatment of choice for kidney failure patients deemed suitable for surgery. In a systematic review and meta-analysis of 48 published cohort studies, any recipient of a living donor kidney had superior all-cause mortality compared to recipients of other kidney allografts or remaining waitlisted on dialysis [1]. This mirrors national registry data, with superior ten-year patient and graft survival reported after living donor kidney transplantation versus deceased donor kidney transplantation [2].

Despite these benefits, living donor kidney transplant rates have stagnated over the last decade in many kidney transplant programs. In the United Kingdom, living donor transplant rates have dropped by a quarter over the last decade, from a peak of 1,036 adult living donor kidney transplants in the year 2013/2014 to 789 in the last available year of 2021/2022 [3]. While some of this may relate to recovery processes post pandemic, it is notable that living donor kidney transplant rates pre-pandemic in 2019/2020 were only 954. Therefore, a key component of the latest NHS Blood and Transplant (NHSBT) strategy document encourages expansion of living donor kidney transplantation activity [4]. To that effect, promoting living kidney donation among older individuals is very attractive. Bailey et al. report the number of living kidney donors aged ≥65 years has risen from 4% to 10% between 2006 and 2017 respectively [5]. However, numbers appear to have plateaued since then. According to national registry data, while 18% of all living donor kidney donors were aged ≥60 years between 2010 and 2016 [6], this has remained static at 20% between 2016 and 2022 [3].

The literature regarding survival outcomes for kidney transplant candidates receiving older living donor kidneys is not clear. In a systematic review of published studies, living donor age stratified at 60 years was associated with 1-year graft loss for recipients but no significant findings were observed for either 1- or 3-year recipient mortality or graft loss at a lower donor age stratification of 50 years [7]. However, the meta-analysis for mortality was conducted on three small studies for publications between 1989 and 2010, which severely limits its utility and interpretation. Other work has associated older living donor age as a risk factor for graft loss and/or mortality when compared to a younger living donor [8, 9]. However, this is not a useful comparison as many kidney transplant candidates will not have a choice between an older or younger living donor. More relevant is whether survival outcomes differ when comparing receipt of an older living donor kidney versus receiving a standard criteria donor (SCD) kidney. This is an important question which kidney transplant candidates may be faced in the real-world and there is a paucity of contemporary literature to guide counselling on this matter. Therefore, the aim of this analysis was to explore this question using UK transplant registry data, with older living donors defined as any donor aged 60 years and above.

The literature reports heterogenous outcomes for recipients of older living donor kidneys, dependent upon whether comparisons are made with different types of deceased donor allografts or younger living donors. From a practical perspective, the key question is whether waitlisted kidney transplants candidates likely to receive SCD kidneys have any survival advantage or disadvantage to proceed with an older living kidney donor versus a SCD kidney. In our contemporary population cohort study, our findings suggest receiving an older living donor kidney (aged ≥60 years) is associated with lower mortality and risk of graft loss versus receiving an SCD kidney. On sensitivity analyses with older living donor age stratified, all older living donor age groups provide a mortality benefit except receiving a kidney from a living donor aged ≥70 years, which was associated with higher mortality compared to receiving a SCD kidney (but equivalent mortality when compared to receiving an ECD kidney).

Disparate outcomes from previous studies reflect era effects, variable definitions, diverse study populations, methodological differences, and different study comparators (e.g., recipients of younger living donor or SCD kidneys). Favorable outcomes are reported in a 1990–2010 cohort from the United States, where 219/97,782 (0.2%) of all living kidney donors were identified as aged older than ≥70 years [9]. No statistically significant difference in recipient survival was seen between those who received kidneys from living kidney donors aged ≥70 years versus matched recipients of kidneys from younger living kidney donors aged 50–59 years (HR 1.31, 95% CI 0.95–1.69). When compared to matched recipients of SCD kidneys from deceased donors aged 50–59 years, no statistically significant difference in patient survival was seen (HR 0.79, 95% CI 0.60–1.03) [9]. Although not statistically significant, the effect sizes are clinically significant and likely to reflect type 2 statistical errors in view of low sample size. A subsequent registry analysis using data from the United Network for Organ Sharing (UNOS) dataset between 1994 and 2012 was undertaken by Englem et al., with 4.4% of the living donor cohort (4,186/92,646) aged ≥60 years (3.2% aged 60–64 years; 1.0% aged 65–69 years; 0.2% aged ≥70 years) [12]. Compared to SCD recipients, no difference in overall graft survival was observed between living donors aged 65 years or older but risk for death-censored graft loss was higher. Transplant recipients with older living donor kidneys had significantly lower graft and overall survival compared to younger living donor recipients.

Examining a contemporary cohort is important, as era effects may be present. Iordanous et al. identified inferior patient and graft survival for recipients of older (aged 60–85 years) versus younger (aged 30–55 years) living donor kidneys in a systematic review and meta-analysis of study cohorts published between 1980 and 2008, although survival differences dissipated in the 2000s [13]. In subsequent work by the same group using data from Ontario, Canada between 2000 and 2008, no significantly increased risk for death (HR 1.83, 95% CI 0.96–3.48, p = 0.07) or graft-censored graft loss (HR 0.71, 95% CI 0.32–1.56, p = 0.39) was observed with median follow up 4 years for older living kidney donors (aged ≥60 years) versus SCD kidney recipients [14]. However, the hazard ratio was not proportional and increased with time, meaning uncertainty for longer outcomes. This is consistent with data from the Scientific Registry of Transplant Recipients (SRTR), which demonstrate 10-year adjusted hazard ratios for death or graft loss among recipients increase in a non-linear fashion with increasing living donor age and is highest among the ≥60 years group (compared to the reference of living donors aged 18–30 years) [15].

When compared to published data, our results provide reassurance that older living kidney donors provide a survival advantage for kidney transplant candidates versus receiving a SCD (but survival disadvantage if the living donor is aged ≥70 years). For candidates more likely to receive ECD kidneys, there is survival advantage using an older living kidney donor (and survival equivalence if the living donor is aged ≥70 years). Utilization of living donors aged ≥70 years, while a small proportion of the overall living donor cohort, requires careful matching of donors and recipients to facilitate optimized outcomes. One suggestion is to avoid extreme age differences when considering living donors aged ≥70 years. In a small single-center study, Hiramitsu et al. observed living donor kidney transplantation from donors aged 70–89 years to recipients with a donor-recipient age difference of 10–15 years was an independent risk factor for graft loss and recipient mortality [8]. This complements our analyses and suggest living kidney donors aged ≥70 years are an appropriate choice for kidney transplant candidates likely to receive ECD kidneys but not SCD kidneys (or any candidate if compared to dialysis).

This is an important and topical question, especially as countries strive to expand living donor numbers. In the United States, data from the SRTR show living kidney donors aged ≥55 years have been the fastest growing cohort among all living kidney donor activity and are now the second commonest age group between 40 and 54 years (which has been slowly declining) [16]. If living donor activity can successfully increase, especially among older adults as potential donors, then our data can influence decision making for optimized patient counselling. Parallel to discussions about recipient survival outcomes are the safety outcomes associated with using older living kidney donors. Although low among living kidney donors, cumulative 15-year incidence of end-stage kidney disease per 10,000 varies significantly by age and is highest for donors aged ≥60 years 70.2 (95% CI 30.4–161.8, p < 0.001) [17]. Some of this risk may be due to an age-related sluggish physiological response by the contralateral kidney after donor nephrectomy. In a retrospective single-center analysis, Bellini et al. observed slower recovery of kidney function for living donors aged ≥60 years and higher percentual difference in estimated glomerular filtration rate (eGFR) post-donation [18]. This was consistent with findings from a systematic review and meta-analysis of 31 published studies [19]. While low eGFR is an independent risk factor for cardiovascular disease and all-cause mortality, any increased risk for these outcomes has reassuringly not been observed among older living donors. Analyzing UNOS data, Segev et al. observed no increase in mortality for living kidney donors versus age-matched “healthy” nondonors when stratified by age [3,017/80,347 (3.8%) living donors were aged ≥60 years] [20]. Reese et al., specifically matched older living kidney donors (mean age 59 years) from the UNOS dataset to healthy older individuals in the Health and Retirement Study, finding no difference in risk for cardiovascular disease or death. In summary, older age per se should not be considered a contra-indication to being a living kidney donor [21]. However, rigorous selection criteria is warranted and careful donor-recipient matching necessary for optimized outcomes.

Our study has many strengths in comparison to the available published literature. Firstly, our cohort of 2000–2019 is more contemporary than previous studies, reflecting current clinical practice and selection criteria. Many allocation systems aim to match like-for-like for donors and recipients like the United Kingdom, which should make these results translatable to other countries with similar allocation policies. Secondly, we have utilized different statistical approaches to test for robustness. It is reassuring to observe the take-home messages from our analyses are generally consistent across all statistical models used and reinforces our primary study findings. Limitations of this study must also be appreciated for accurate interpretation of the results. As an intention-to-treat analysis, we did not factor for waitlisted kidney failure patients who were suspended or removed from the waiting list due to lack of fitness. This could lead to informative-treatment bias, i.e., where the pool of transplants recipients is systematically different from the remaining-on-dialysis comparator group. Censoring patients at delisting would have yielded an overestimation of survival on dialysis as data from the United Kingdom confirms increased mortality associated for waitlisted kidney failure patients who experience any period of suspension [22]. This analysis comprised waitlisted kidney transplant candidates who either had their primary transplant or remained on dialysis; therefore it provides no targeted evidence in the setting of advanced chronic kidney disease or a failed kidney transplant exploring repeat transplantation. Lack of data relating to medical co-morbidities or dialysis vintage limits interpretation of survival probabilities in the setting of specific health burdens, which may tip the balance of more borderline risk versus benefit calculations for recipients of older living kidney donors. Residual confounding is an important but inevitable limitation of retrospective registry analyses despite adjusted statistical analyses. This is certainly the case in this analysis due to unavailable data and unmeasured confounders. Finally, this analysis has focused solely upon survival benefits associated with transplant surgery for kidney failure patients and overlooks the importance of quality of life which was beyond the scope of this study but is under investigation elsewhere [23].

To conclude, in this contemporary national cohort study of kidney failure patients listed for transplantation, proceeding with an older living donor kidney transplant affords a survival benefit to kidney transplant candidates when compared to receiving a standard criteria donor kidney or remaining on dialysis. While our data is reassuring, the caveat remains that survival benefits at a population-level must be translated to individual kidney transplant candidates with personalized risk counselling (e.g., using living donors aged ≥70 years). However, our data provides reassurance to clinicians involved in the care of kidney failure patients that older living donor candidates are an untapped pool of potential kidney donors that should be actively pursued.