Survival Outcomes Following Preemptive vs Nonpreemptive Kidney Transplantation.

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 m2 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.