Introduction: Preemptive kidney transplantation is widely promoted as the optimal treatment for kidney failure.Proposed benefits include avoiding dialysis-related morbidity and improving survival.However, prior studies are limited by lead-time, selection, and confounding biases.We emulated a target trial to estimate the causal effect of preemptive vs. non-preemptive transplantation on mortality and graft outcomes in a large national cohort.Methods: We designed the study following target trial principles aligned with the TARGET statement.Eligible participants were first kidney-alone transplant recipients in the U.S. Scientific Registry of Transplant Recipients (SRTR) preemptively wait-listed from 2005 to 2015 and transplanted before November 2023.Treatment strategies were (1) preemptive transplantation (before starting chronic dialysis) and ( 2) non-preemptive transplantation.Time-zero was defined as the date eGFR first reached #20 mL/min/ 1.73 m 2 , representing biologic eligibility for transplant.Follow-up continued until death, graft loss, or administrative censoring.The primary outcome was all-cause mortality; secondary outcomes were allcause graft failure (ACGF) and delayed graft function (DGF: dialysis #7 days or <25% creatinine decline #24 h post-transplant).A logistic regression model estimated each recipient's probability of preemptive transplant using demographic, clinical, socioeconomic, donor, year, and centre variables.Stabilized truncated weights achieved covariate balance (standardized mean differences < 0.10).We estimated the as-treated effect using inverse probability of treatment weighting (IPTW) and left-truncated Cox proportional hazards models for mortality and ACGF, with patients entering the risk set at transplant to address selection bias and align follow-up from a shared timezero, mitigating lead-time bias.DGF was analyzed with a weighted logistic regression model.Sensitivity analyses adjusted for donor variables and clustering by centre and year; subgroups analyses were performed by donor type, donor age, and recipient age.Results: Among 32,770 recipients (15,894 48.5% preemptive; 265,369 person-years), crude analyses suggested a survival benefit of preemptive transplantation (HR 0.75 95% CI 0.71, 0.79) that attenuated after left truncation (HR 0.88 0.84, 0.92) or IPTW (0.95 0.90, 1.00) and disappeared in the final model (HR 1.01 0.96, 1.07).Results were consistent across donor type, age, and sensitivity analyses.Preemptive transplantation modestly lowered ACGF risk (HR 0.95 0.91, 1.00) and reduced DGF (OR 0.68 0.64, 0.71), particularly among deceased donor kidney transplants (OR 0.56 0.52, 0.59) and older recipients, with a signal toward greater benefit for transplants from older donors.Conclusion: In this target trial emulation, preemptive kidney transplantation conferred no long-term patient or all-cause graft survival advantage after correction for lead-time, selection, and confounding biases.Although preemptive transplantation reduced DGF -especially among deceased-donor kidneys and older recipients -these short-term gains did not yield lasting survival benefit.Our findings provide greater support for allocation policies prioritizing clinical urgency over preemptive status.I have no potential conflict of interest to disclose.I did not use generative AI and AI-assisted technologies in the writing process.
Natarajan et al. (Wed,) studied this question.