Sodium Levels Can Help Predict Outcomes before and after Liver Transplantation

Two studies published in the current issue of Liver Transplantation (August 2007) examine whether sodium levels can be used to predict mortality while awaiting and following liver transplantation.

The most appropriate system for organ allocation for liver transplants is a subject of ongoing controversy. In the U.S., the Model for End-Stage Liver Disease (MELD) system was introduced in 2002 as a way to prioritize patients with the highest risk of death. Since that time, waiting list mortality and waiting times have decreased, with no negative impact on post-transplant survival.

The MELD score is based on objective and readily available variables, but in recent years many researchers have suggested adding additional factors to improve the model's prognostic accuracy.

Hyponatremia (low blood sodium level) is a strong predictor of wait-list mortality, but it has also been associated with worse post-transplant outcomes. The 2 recent studies examined whether incorporating sodium levels into the MELD model can help better predict outcomes for patients with severe liver disease.

Study 1

In the first study [1], researchers led by Angelo Luca, MD, of the Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione in Palermo, Italy and Bernhard Angermayr, MD, of the Medical University of Vienna in Austria analyzed the records of 310 patients who underwent placement of a transjugular intrahepatic portosystemic shunt (TIPS) between 1999 and March 2005 at 2 European centers.

They developed a model dubbed "integrated MELD" (iMELD) that incorporates both sodium levels and patient age. The model was then tested in 451 patients with cirrhosis who were on liver transplant waiting lists.

The results showed that both sodium level and age are accurate predictors of prognosis, independent of the MELD score.

The authors noted that both sodium level and age are objective, reliable, and readily available variables that may be useful in defining the priority of liver allocation as part of the iMELD model.

However, they said, "the inclusion of age into the iMELD might raise some ethical issues in this set of patients also because conflicting data exist on the risk of postoperative death in elderly liver transplant recipients."

Study 2

In the second study [2], researchers led by M.F. Dawwas, of Cambridge University Hospital NHS Foundation Trust examined sodium levels in 5152 patients in the U.K. and Ireland who underwent liver transplantation between 1994 and 2005.

The researchers found that the blood sodium level measured immediately prior to transplantation was an independent predictor of mortality following the transplant.

"Although the detrimental impact of both severe recipient hyponatraemia and hypernatraemia [high blood sodium] on post-transplant survival was confined to the first 90 days, they also had deleterious effects on the frequency of postoperative complications, functional status and resource utilization even among those who survived this period," the authors stated.

The finding that patients with high sodium levels (who comprised a very small percentage) fared worst had not been previously published.

The authors noted that the reduced survival following liver transplantation in patients with severe hyponatremia strongly suggests the importance of correcting sodium levels before surgery, although the question of whether bringing sodium levels into the normal range will improve transplant outcomes requires further study.

They noted that severe hyponatremia had a greater impact on wait-list mortality than post-transplant mortality, and concluded that "a liver allocation scheme prioritizing organs to hyponatraemic recipients might be likely to maximize survival benefit from the procedure."

In an accompanying editorial in the same issue [3], Scott W. Biggins, MD, of the University of California at San Francisco wrote that carefully applying models that predict mortality after transplantation is a promising tool for further optimizing liver allocation.

The 2 studies, he stated, "solidify the importance of [sodium] as predictor of urgency for, and risk from, [liver transplantation] and fuel the debate over how to apply these risk assessments to rational improvements in liver graft allocation."

Regarding the question raised in the first study as to whether a transplant candidate's age should be considered for organ allocation, Biggins noted that as donor organ quality and post-transplant mortality risk models improve, a system that matches specific donor and recipient characteristics may improve the usefulness of liver transplants.

He noted that the second study presents new data important in balancing the urgency for transplantation with post-transplant outcomes. "If incorporating [sodium] into an allocation model could better predict severity of illness, then perhaps hyponatremic patients would undergo transplant before their clinical state adversely impacted their post-transplant outcome," he wrote.

"The onus is on the transplant community to continuously refine the allocation system such that livers are targeted to patients who need them most without sacrificing the overall utility of this limited resource to society," he concluded.

Liver Transplantation is the official journal of the American Association for the Study of Liver Diseases (AASLD) and the International Liver Transplantation Society (ILTS). The journal is published on behalf of the societies by John Wiley & Sons, Inc. and is available online via Wiley InterScience.

08/07/07

References

1. A Luca, B Angermayr, G Bertolini, and others. An Integrated MELD Model Including Serum Sodium and Age Improves the Prediction of Early Mortality in Patients with Cirrhosis. Liver Transplantation. August 2007. (DOI: 10.1002/lt.21197).

2. M F Dawwas, J D Lewsey, J M Neuberger, and others. The Impact of Serum Sodium Concentration on Mortality after Liver Transplantation: A Cohort Multicenter Study. Liver Transplantation. August 2007. (DOI: 10.1002/lt.21154).

3. S W Biggins. Beyond the Numbers: Rational and Ethical Application of Outcome Models for Organ Allocation in Liver Transplantation (Editorial). Liver Transplantation. August 2007. (DOI: 10.1002/lt.21210).