Reese, Peter P.

Importance Accurate prediction of patient mortality after kidney transplant is an unmet need. Objective To develop and validate an integrative prediction model that predicts short- and long-term patient mortality for kidney recipients. Design, Setting, and Participants This international cohort study included patients who underwent transplants between 2004 and 2023 from 14 academic medical centers from Europe and the US. The derivation cohort consisted of 1566 consecutive adult kidney recipients in a deeply phenotyped cohort prospectively recruited in 1 French center between 2004 and 2014. External validation cohorts consisted of 10 951 kidney recipients from 7 centers in France, 3 centers in Europe, and 3 centers in North America who underwent kidney transplants between 2006 and 2023. Data were analyzed from January 2023 to June 2025. Main Outcome and Measures All-cause mortality was assessed, and 121 candidate prognostic factors, comprising demographics and clinical, biological, imaging, and immunological parameters, were collected. Results Among 12 517 kidney transplant recipients, including 1566 in the derivation cohort (mean [SD] age, 50.05 [14.31] years; 942 male [60.15%]) and 10 951 in validation cohorts (mean [SD] age, 53.32 [13.97] years; 6766 male [61.78%]), 2486 patients (19.9%) died after a median (IQR) follow-up of 5.08 (2.97-7.00) years. Fourteen prognostic factors (including clinical, biological, and imaging risk factors) were independently associated with patient death (eg, patient age: hazard ratio per 1-year increase in age, 1.07 [95% CI, 1.06-1.08]; P < .001) and were combined into a risk prediction model (mBox). The model exhibited accurate calibration and discrimination in the derivation cohort, with C statistics of 0.82 (95% CI, 0.77-0.87) and 0.80 (95% CI, 0.78-0.82) at 1 and 10 years, respectively, after the transplant. Abbreviated models were developed and validated to ensure model generalizability. Performance of abbreviated models was confirmed in external validation cohorts from France (C statistic, 0.76 [95% CI, 0.73-0.78]), Europe (C statistic, 0.74 [95% CI, 0.72-0.76]), the US (C statistic, 0.74 [95% CI, 0.70-0.78]), the Greater Paris University Hospital database (C statistic, 0.79 [95% CI, 0.77-0.81]), and the University of California at San Francisco database (C statistic, 0.70 [95% CI, 0.65-0.74]). The model was also validated in a series of subpopulations (eg, women vs men: C statistic, 0.81 [95% CI, 0.77-0.84] vs 0.79 [95% CI, 0.77-0.82]) and clinical scenarios (eg, before COVID-19 era: C statistic, 0.79 [95% CI, 0.77-0.81]) with good and stable performance. Conclusions and Relevance In this study, an accurate prediction model for mortality among kidney recipients, computable at the time of transplant, was developed and externally validated. Results suggest that this model may help stratify patient risk of death, allowing for improved medical decisions.

Key Points Nonimmunologic AKI-related rehospitalizations post–kidney transplant are associated with poorer long-term allograft and recipient outcomes. These data are not reported to United Network for Organ Sharing, and there are no datasets highlighting this important association; thus, our findings are valuable to clinicians. We hope to help the community create a cohort of higher risk transplant patients who need closer monitoring to potentially increase graft longevity Background AKI is associated with an increased risk of CKD and ESKD. However, only limited studies have investigated the effect of AKI episodes on kidney transplant outcomes. This study evaluated the effect of rehospitalization associated with nonimmunologic AKI on long-term outcomes. Data on rehospitalization with AKI after kidney transplant are not reported to United Network for Organ Sharing, and thus, there are no large datasets available to study this association. Methods We completed chart reviews of 989 deceased donor kidney transplant recipients transplanted from 2010 to 2014 at 13 transplant centers in the Deceased Donor Study Consortium. Rehospitalizations up to 5 years post-transplant were included. The cause of rehospitalizations was adjudicated by a transplant nephrologist on the basis of the discharge diagnosis. Primary outcomes were the effect of AKI-related rehospitalization on death-censored graft failure and all-cause mortality. We excluded rehospitalizations because of acute rejection from the primary analysis. The cohort was linked to data from Organ Procurement and Transplantation Network supplied by United Network for Organ Sharing. Time-varying cox-proportional hazard models were used to examine the association between rehospitalization and outcomes. Results We identified 200 (20%) recipients with at least one rehospitalization associated with AKI, 516 (52%) with rehospitalizations without AKI, and 273 (28%) without a rehospitalization post-transplant. Delayed graft function, donor age, and kidney donor profile index score differed between the three groups. We found a higher risk of death censored graft failure adjusted hazard ratio (aHR) 7.5 (95% confidence interval [CI], 4.0 to 13.8), all-cause graft failure aHR 6.7 (95% CI, 4.2 to 10.8), and all-cause mortality aHR 5.7 (95% CI, 2.7 to 11.8) for rehospitalizations associated with AKI compared with no rehospitalization. The non-AKI rehospitalizations also had significantly higher rates of measured outcomes; however, the associations were not as strong. Conclusions AKI rehospitalizations were associated with a significantly increased risk of poorer graft outcomes, and thus, closer follow-up of this high-risk group is warranted.

Abstract The authors have requested that this preprint be removed from Research Square.