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Deceased Donor Kidney Transplantation Versus Continued Dialysis Among Patients Aged 75 Years or Older: A Target Trial
Napat Leeaphorn1, Rose Mary Attieh1, Katherine M Oshel1
1Department of Transplant, Mayo Clinic, Jacksonville, Florida.
Rationale & Objective:
The survival benefit of deceased donor kidney transplantation (DDKT) versus continued dialysis among patients aged ≥75 years remains uncertain due to a lack of randomized trials and limitations of observational study. This study estimated the causal effect of DDKT on survival using a target trial emulation.
Study Design:
Target trial emulation with sequential trials framework.
Setting & Participants:
Transplant-eligible adults aged ≥75 years who initiated dialysis and were listed in the Organ Procurement and Transplantation Network registry (2015-2023) for kidney-only transplantation.
Exposure:
DDKT versus remaining on dialysis.
Outcome:
Restricted mean survival time (RMST) at 3 and 5 years.
Analytical Approach:
The stacked dataset from all auxiliary trials analyzed using weighted Cox proportional hazards regression. Inverse probability of treatment and censoring weights incorporated to address confounding and immortal time bias.
Results:
Among 2,670 patients (mean age, 76.8 years; 70.7% male; 49% with diabetes), 1,012 (37.9%) received DDKT. The framework generated 511 auxiliary trials with 505,438 person-trial observations. DDKT recipients experienced early mortality risk (HR, 2.29 [95% CI, 1.50-3.49] for days 0-90) transitioning to survival benefit beyond 1 year (HR, 0.34 [95% CI, 0.26-0.45] after 3 years). At 3 years, the break-even point, survival was equivalent between groups (RMST difference, 2.0 days; P = 0.9). By 5 years, DDKT conferred a 111-day survival advantage ([95% CI, 65.6-156.4], P < 0.001). Patients without diabetes experienced a numerically greater benefit than patients with diabetes (133.6 vs 81.2 days; P interaction = 0.3), as did those who received ≥2 years dialysis versus <2 years (156.1 vs 107.9 days; P interaction = 0.3).
Limitations:
Unmeasured confounding, generalizability limited to wait-listed patients, most covariates measured at listing rather than updated over time, lack of data on quality of life, symptom burden, or patient-reported outcomes.
Conclusions:
DDKT confers a survival benefit to wait-listed patients aged ≥75 years although this benefit emerges only after 3 years, providing a critical benchmark for patient counseling. The modest 5-year advantage for DDKT should be weighed against earlier elevated risks of mortality. These findings support individualized decision-making and highlight dialysis as a reasonable alternative to DDKT.
Plain-Language Summary:
Kidney transplantation is the preferred treatment for kidney failure, but whether it benefits patients aged 75 and older remains unclear. Previous studies in this age group have been limited by biased methods. This study used target trial emulation to mimic a randomized trial using national registry data, allowing estimation of transplantation's true effect on patient survival. We found that transplant recipients face a higher mortality risk in the first few months after surgery, but those who survive this early period live longer than patients continuing to receive dialysis. This survival advantage becomes clear after about 3 years of follow-up. These findings can help elderly patients and their nephrologists make more informed decisions and emphasize that age alone should not exclude patients from consideration for kidney transplantation.
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