Renal Function Parameters and Serum Sodium Enhance Prediction of Wait-List Outcomes in Pediatric Liver Transplantation

Background and Aims: Reliance on exception points to prioritize children for liver transplantation (LT) stems from concerns that the Pediatric End-Stage Liver Disease (PELD) score underestimates mortality. Renal dysfunction and serum sodium disturbances are negative prognosticators in adult LT candidates and various pediatric populations, but are not accounted for in PELD. We retrospectively evaluated the effect of these parameters in predicting 90-day wait-list death/deterioration among pediatric patients (<12 years) listed for isolated LT in the United States between February 2002 and June 2018. Approach and Results: Among 4,765 patients, 2,303 (49.3%) were transplanted, and 231 (4.8%) died or deteriorated beyond transplantability within 90 days of listing. Estimated glomerular filtration rate (eGFR) (hazard ratio [HR] 1.09 per 5-unit decrease, 95% confidence interval [CI] 1.06-1.10) and dialysis (HR 7.24, 95% CI 3.57-14.66) were univariate predictors of 90-day death/deterioration (P < 0.001). The long-term benefit of LT persisted in patients with renal dysfunction, with LT as a time-dependent covariate conferring a 2.4-fold and 17-fold improvement in late survival among those with mild and moderate-to-severe dysfunction, respectively. Adjusting for PELD, sodium was a significant nonlinear predictor of outcome, with 90-day death/deterioration risk increased at both extremes of sodium (HR 1.20 per 1-unit decrease below 137 mmol/L, 95% CI 1.16-1.23; HR per 1-unit increase above 137 mmol/L 1.13, 95% CI 1.10-1.17, P < 0.001). A multivariable model incorporating PELD, eGFR, dialysis, and sodium demonstrated improved performance and superior calibration in predicting wait-list outcomes relative to the PELD score. Conclusions: Listing eGFR, dialysis, and serum sodium are potent, independent predictors of 90-day death/deterioration in pediatric LT candidates, capturing risk not accounted for by PELD. Incorporation of these variables into organ allocation systems may highlight patient subsets with previously underappreciated risk, augment ability of PELD to prioritize patients for transplantation, and ultimately mitigate reliance on nonstandard exceptions.