Waitlist Time, Age, and Social Vulnerability: Impact on the Survival Benefit of Deceased Donor Kidney Transplantation Versus Long-term Dialysis Among Patients With End-stage Renal Disease

Yang et al1 used restricted mean survival times (RMSTs) to analyze the survival benefit resulting from transplantation, restricted to the 5-y period after transplant, and analyzed the associations between this statistic and patient characteristics. The authors demonstrated that the RMST can be a useful approach to work with the nebulous concept of the benefit of a therapy such as transplantation. As with every analysis, assumptions and technical issues need to be carefully considered when interpreting results. Expected survival is a natural way to assess the benefit of a procedure such as transplantation. Although it is always true that individual experiences vary, assessing the expected survival benefit in terms of life expectancy can be useful when assessing the impact of a therapy on a large population. "Extra years of life" is more easily understood by patients than other statistical methods to express similar concepts, such as adjusted odds ratios, hazard ratios, or standardized survival probabilities. Years of life are easier to translate into resource needs, such as years on immunosuppressive therapy or dialysis. Expressing transplant benefits as "life-extending" instead of "life-saving" might aid understanding of the benefits of this procedure and avoid the incorrect implication that a kidney transplant restores a dialysis patient to the same life expectancy and quality of life as a healthy person without kidney failure. The primary issue with the RMST is that unless there are sufficient data to calculate it for the entire life expectancy of the patients, an artificial cutoff needs to be set. Yang et al1 set this for 5 y, and this may have affected their results, overemphasizing the survival benefits for the patients with the lowest waitlist survival. Yang et al1 came to the surprising conclusion that the survival benefit resulting from transplantation is higher for older adults. This contradicts previous studies by Wolfe et al2 that showed the opposite results. The primary reason for the contradictory results is that an earlier cutoff for the life expectancy calculation can erase much of the RMST benefit for the younger population (as illustrated in Figure 1 from the study by Wolfe et al2). The expected 5-y survival rate for dialysis patients aged between 18 and 21 y was 94% (2023 United States Renal Data System Annual Data Report [USRDS ADR],3 Table I.11). There is just less room for survival benefit for the younger patients within the 5-y window. On the other hand, only 29.6% of 70- to 74-y-old patients survive a similar period, which makes it easier for transplantation to demonstrate its substantial benefit for this population even within this short window. Yang et al1 should not necessarily be faulted for their decision to use a specific window because calculating the RMST using extremely long survival windows can present a substantial technical challenge and may lead to bias. If they used a long enough time period to demonstrate the full benefit of transplantation, they would need to either extrapolate survival or use patient populations from further back in time, possibly both. The former approach involves extrapolation beyond the available data, which is always problematic. Using data from transplants occurring far in the past, we need to account for the fact that survival has been improving over time, possibly as a result of advancements in medicine. Five-year deceased-donor transplant survival rate has increased from 65.7% for patients transplanted in 2001 to 76.3% for 2016 transplants, adjusted for age and other factors (2023 USRDS ADR,3 Table I.29), and there is no reason to believe that posttransplant survival will not improve further in the future. Yang et al1 made a decision to restrict their analyses to data after 2008, possibly because older data are less relevant to today's transplant experience. The authors also found that waitlist time is positively associated with greater transplant benefit. Other publications consistently show that time on dialysis negatively impacts posttransplant survival,4,5 but this might be offset by the negative effect that extended time on dialysis has on waitlist survival,6 indicating a possible net benefit. Patients from more vulnerable geographic regions (eg, regions with greater social vulnerability, as measured by various indices) tended to have lower RMST than patients in less vulnerable regions. The posttransplant survival was similar (Figure 3A), but the waitlist survival was "better" for the patients in more vulnerable areas,1 which is counterintuitive. As the authors noted, before 2023, Medicare coverage for immunosuppression ended 3 y after transplant, which meant that patients without additional coverage or the means to pay for immunosuppression themselves were less likely to be waitlisted. It might be the case that among the poorest populations, patients who were young and had the additional coverage coming from employment would be more likely to be waitlisted, and so these results could reflect more of an age effect than an association between social vulnerability and improved waitlist survival. The changes to Medicare coverage rules in January 2023 noted by the authors may impact these waitlisting patterns and the resulting RMST. The contributions made by Yang et al1 are notable and their approach should be considered for future assessments of the benefits of transplantation. As with all approaches, careful consideration of the assumptions should be incorporated into the interpretation of the results.