Weight Loss Intentionality and Frailty are Associated with Pre-Kidney Transplant Outcomes

Background: Unintentional weight loss, a hallmark of frailty, predicts worse post-kidney transplantation (KT) outcomes. However, weight loss in candidates with obesity is often recommended to enhance transplant eligibility. We tested whether pre-evaluation weight change is associated with listing/waitlist mortality, considering intentionality and frailty. Methods: We leveraged data on body mass index (BMI), weight loss intentionality, (one-year pre-evaluation and at evaluation), and frailty (four-component Physical Frailty Phenotype at evaluation) for 1,361 candidates (895 listed) with obesity (BMI≥30kg/m 2 ) enrolled in a prospective multi-center cohort study. We estimated the association between pre-evaluation weight change (stable, gain, unintentional/intentional loss) with chance of listing/waitlist mortality using Cox proportional hazards/competing risk models. Results: Among candidates with obesity, 48% had stable weight, 17% had weight gain, 16% had unintentional weight loss, and 20% had intentional weight loss over the year prior to evaluation. Among frail candidates with obesity, stable weight was associated with 27% lower chance of listing (adjusted hazard ratio [aHR]:0.73,95% confidence intervals [CI]:0.55-0.96), weight gain with 47% lower chance of listing (aHR:0.53,95%CI:0.34-0.80), and unintentional weight loss with 48% lower chance of listing (aHR:0.52,95%CI:0.32-0.84) compared to non-frail candidates with stable weight. However, in frail candidates with obesity, intentional weight loss was not associated with a significantly lower chance of listing compared to non-frail candidates with stable weight. Additionally, among frail candidates with obesity, stable weight (adjusted sub-hazard ratio [aSHR]:1.72,95%CI:1.01-2.90), unintentional weight loss (aSHR:2.78,95%CI:1.23-6.27), and intentional weight loss (aSHR:2.26,95%CI:1.05-4.85) were associated with higher waitlist mortality compared to non-frail candidates with stable weight. Among non-frail candidates, no associations were observed for weight change and frailty status with either chance of listing or waitlist mortality. Conclusion: Among frail candidates with obesity, unintentional pre-KT weight loss is associated with lower chance of listing; however, any weight loss is associated with higher waitlist mortality. Our findings suggest that frail candidates with obesity may benefit from clinician supervision of pre-KT weight loss.