It Takes 2 to Match

The discrepancy between supply and demand represents one of the most challenging issues in organ transplantation. An optimized organ utilization and “ideal” matching of available organs with those patients benefitting most is thus of utmost clinical relevance. Approximately 50 000 patients were added to the kidney transplant waitlist in the United States in 2024, whereas <29 000 individuals had received transplanted organs.1 This discrepancy underscores the need to balance utility and equity to ensure the best possible care to each and every patient while using available kidneys effectively. Ultimately, the goal is to transplant those who are most likely to benefit while being responsible stewards of the scarce supply of donor organs. Currently, graft quality is assessed solely by donor characteristics through classification systems, including the Kidney Donor Profile Index (KDPI). However, a combinatorial analysis accounting for graft quality and patient risks and benefits more objectively may improve the decision process. In the current issue of Transplantation, Choisy et al2 proposed a score that includes recipient characteristics, which may modify aspects of donor quality. The authors deployed a robust modeling framework using data spanning >20 y based on a study population recruited from multiple French transplantation centers, totaling >30 000 person-years of follow-up. Their score shows a nonlinear relationship with recipient age, suggesting that middle-aged recipients (40–60 y) tend to have better outcomes. Older and younger recipients, at the same time, experienced higher risks of death and graft failure when receiving marginal kidneys. Interestingly, these findings are not in line with previous publications. Notably, older patients demonstrated satisfactory outcomes following an “old-to-old” match, mitigating the heightened immunogenicity of older donor organs by placing them into recipients with a less robust alloimmune response.3 Moreover, a recent study by Coemans et al,4 based on a large cohort of European and US patients, examined continuous combinations of donor and recipient ages. The study concluded that increasing donor age, often considered the best proxy for graft quality, is generally associated with a higher risk of return to dialysis and retransplantation. However, this effect was significantly less pronounced in older recipients. In contrast, death with a functioning graft had not been driven by donor age predominantly, suggesting a limited advantage of allocating younger organs to older recipients. This observation also aligns with the differing demands for graft longevity across recipient age groups. For instance, the life expectancy of a 40- to 44-y-old male kidney transplant recipient is approximately 24.6 y, compared with “just” 10.3 y for a 65- to 69-y-old recipient, highlighting that younger patients require grafts capable of sustaining organ function over a longer period.5 Indeed, Bae et al6 found that patients with a better Estimated Post-Transplant Survival Score who are generally younger derive less benefit from marginal organs. Conversely, patients with a less favorable Estimated Post-Transplant Survival score (those patients are generally older) gain a clear survival benefit when receiving grafts with a higher KDPI. In fact, an increased utilization of marginal organs based on higher KDPI scores is expected to improve not only survival but also treatment cost utility for older patients with end-stage renal disease (ESRD).7 The findings of Choisy et al add valuable information to this debate, representing a first step toward establishing a combinatorial marginality assessment. Ultimately, such a score should be validated and expanded in larger, multicenter patient cohorts, with the aim of incorporating a broader range of donor and recipient characteristics beyond chronological age (Figure 1). Possible explanations for the findings by Choisy et al, which are, at least in part, not in line with most published literature, may be linked to the inherent limitation of studies that compare patient populations with fundamentally different survival trajectories, such as recipients from different age groups due to differential censoring. The limited median follow-up time of 11.1 y, as reported in their study, may thus underestimate the long-term impact of marginal donor organs in recipients with longer life expectancy, including younger patients, since outcome differences may only become obvious after a longer period. For instance, in the United States, 60.2% of 40- to 44-y-old deceased donor graft recipients live with functioning grafts by 10 y, compared with “only” 24.4% of recipients aged 70–74 y.5 This may also help explain the limited discriminative performance of their marginality score observed in younger recipients. Another important aspect may lie in the thresholds for organ utilization across different geographic areas, challenging interpretation and comparisons with other studies. For instance, graft utilization in the United States appears to be more conservative, reflected by higher organ discard rates. In fact, 62% of organs discarded in the United States would have been accepted for transplantation in France. Restrictive organ acceptance practices can improve outcomes for individual patients but may have detrimental consequences for the broader ESRD population, as many patients who would still benefit from these organs may not get the opportunity for transplantation.8 Being able to better estimate the combinatorial effect between organ and recipient factors could thus significantly improve predictability, allowing expansion of organ procurement.FIGURE 1.: Transplant outcome assessment based on donor and recipient criteria (figure created in BioRender). ESRD, end-stage renal disease.Timing of transplantation is another important factor one must consider when assessing the benefits and risks of using less-than-ideal donor organs. In many cases, receiving a marginal organ earlier appears critical to avoid the detrimental effects of dialysis rather than waiting for a higher-quality graft or risking not receiving a transplant at all.9 This is particularly relevant for older patients for whom the likelihood of receiving a graft within their lifetime is <50%.10 For instance, in the United States, 40- to 44-y-old male patients with ESRD live an average of 9.7 y on dialysis compared with only 4.5 y for those aged 65–69.5 Therefore, young patients may still benefit from waiting for a better-quality organ, whereas older patients simply cannot afford to decline even a marginal offer. Therefore, many allocation systems aim to promote timely transplantation for older patients by increasing the utilization of marginal organs for these patients.11 Ultimately, increasing the use of older and less-than-ideal donor organs for all but notably older recipients may be the preferred strategy to sustain the current transplant system, given the shifting demographics of both transplant candidates and donors. In fact, during the past 20 y, the number of kidney transplants from donors aged 50–64 y more than doubled (+124.0%) in the United States (from 3849 in 2005 to 8623 in 2024), whereas those from donors aged 65 y or older increased by 203.0% (from 523 in 2005 to 1585 in 2024).1 Up until now, organ allocation has largely focused on the assessment of donor criteria and organ quality. Moving forward, a combinatorial assessment of donor and recipient risk factors will be necessary. Our recent understanding of delayed graft function (DGF) shows the way. As much as the occurrence and severity of DGF have traditionally been solely linked to organ quality and perioperative conditions, more recent studies have also shown that recipient factors are of significance.12 Thus, as in DGF, for organ allocation, it takes 2 to match.