Abstract / Summary
Importance Preemptive kidney transplantation (before dialysis) is promoted as optimal therapy for kidney failure, yet evidence of a true survival advantage remains uncertain due to confounding, selection, and lead-time biases. Objective To estimate the associations of preemptive vs nonpreemptive kidney transplantation with mortality and graft outcomes using a target trial emulation among transplant recipients. Design, Setting, and Participants This retrospective cohort study used data from the Scientific Registry of Transplant Recipients, a nationwide registry of all US kidney transplant centers, from January 1, 2005, to November 30, 2023. Adult first kidney-alone transplant recipients with recorded wait-time start at an estimated glomerular filtration rate (eGFR) of 20 mL/min/1.73 m 2 or less were included. Groups were balanced using stabilized inverse probability of treatment weighting (IPTW) to emulate randomization across demographic, clinical, and socioeconomic factors identified by a directed acyclic graph. Analyses were conducted from July to October 2025. Exposures Preemptive vs nonpreemptive kidney transplantation, defined by dialysis before transplant. Main Outcomes and Measures The primary outcome was all-cause mortality; secondary outcomes were all-cause graft failure, death-censored graft failure, and delayed graft function. IPTW was incorporated for baseline confounding to address selection bias. Weighted Kaplan-Meier curves estimated survival differences; hazard ratios (HRs) and odds ratios (ORs) were derived from weighted left-truncated Cox proportional hazards (to address lead-time bias) and logistic regression models, respectively. Results Among 32 770 recipients (15 894 [48.5%] preemptive [mean (SD) age, 53.7 (13.1) years; 7007 (44.1%) female] and 16 876 [51.5%] nonpreemptive [mean (SD) age, 54.5 (13.0) years; 6978 (41.3%) female]) with more than 265 369 person-years of follow-up, 6827 deaths occurred. Preemptive transplantation showed no mortality benefit (HR, 1.02; 95% CI, 0.96-1.07). The weighted survival differences were approximately 1% to 2% annually. Preemptive transplantation was associated with lower odds of delayed graft function (OR, 0.68; 95% CI, 0.64-0.72) and reduced risk of death-censored graft failure (HR, 0.81; 95% CI, 0.74-0.88), an association largely attenuated after adjustment for delayed graft function. There was no association with all-cause graft failure (HR, 0.96; 95% CI, 0.91-1.00). Conclusions and Relevance In this study, preemptive transplantation was not associated with improved patient survival but was associated with lower rates of delayed graft function and death-censored graft failure. Findings challenge presumed survival advantages and suggest preemptive strategies should focus on preventing early graft dysfunction and optimizing use of high-risk kidneys rather than expected mortality benefit.