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

Abstract

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.

Subclinical cardiac abnormalities in children with biliary atresia correlate with outcomes after liver transplantation

“…However, the PELD score has a limited ability to predict the postoperative mortality of pediatric patients ( 27 ). With the increase in organ allocation based on the PELD exception score, the fairness of the PELD score has been questioned ( 28 ). In our study, we found that elevated LVMI and RWT can predict poor outcomes after liver transplantation.…”

Model for End‐Stage Liver Disease/Pediatric End‐Stage Liver Disease exception policy and outcomes in pediatric patients with hepatopulmonary syndrome requiring liver transplantation

“…[42] It is associated with adverse outcomes for pediatric LT candidates and has been shown to significantly increase risk of death. [43,44] Second, estimated glomerular filtration rate, dialysis status, and serum sodium levels have also been shown to be predictive of 90-day mortality in pediatric LT candidates. [44] A PELD score that incorporates sodium and creatinine levels has been demonstrated to more accurately reflect medical urgency and could better prioritize children with the knowledge that traditional PELD scores significantly underestimate waitlist mortality, especially compared with adult MELD scores.…”

Cardiac and renal effects of liver cirrhosis in a growing animal model

“…Similarly, although total NOS expression was not altered by biliary ligation, a decrease in eNOS expression in the heart was initially observed in comparison to control animals. As cirrhosis progressed, the expression of this gene increased, a phenomenon that has been investigated in many studies [22][23][24] . It was demonstrated that NO resulting from eNOS activity has beneficial effects [22][23][24] .…”

“…As cirrhosis progressed, the expression of this gene increased, a phenomenon that has been investigated in many studies [22][23][24] . It was demonstrated that NO resulting from eNOS activity has beneficial effects [22][23][24] . Therefore, it is possible that some protective or feedback mechanisms attempting to reduce the deleterious effects of cirrhosis in the heart lead to an increase in the eNOS gene expression, in late phases of liver disease.…”

“…In accordance with these findings, clinical practice shows that renal dysfunction is more frequent and intense in cirrhotic adults than in children 23 . This is the reason why the model of end-stage liver disease (MELD) score, used to rank adults eligible to liver transplant, considers creatinine serial levels, while the pediatric end-stage liver disease (PELD) score does not take creatinine levels into account 24 .…”