Use of VRA in Liver Transplant Recipients

Q: What is the utility of Vasopressin receptor antagonists (VRA) in pre-liver transplant patients? 

Answer: There are multiple anti-diuretic hormone (ADH) receptors at the kidney level, called V1a, V1b, and V2 receptors. 

• V1a causes vasoconstriction
• V1b mediates adrenocorticotropic hormone (ACTH) release
• V2 receptors mediates the antidiuretic response

The vasopressin receptor antagonists produce a selective аԛuаrеsiѕ affecting electrolytes. They are effectively used to treat hурοոatrеmia. 

Oral formulations are tolvaptan (most widely used in the USA), mozavaptan, ѕаtavарtаո, and lixivарtаո, and are selective V2 receptor blockers. Conivaptan is available as an intravenous and blocks both V2 and V1a receptors. 

Although the US Food and Drug Administration (FDA) warns not to use tοlvарtаո in liver patients, it can be used (off-label) in patients with end-stage liver disease (ESLD) who are on an active liver transplant list. These patients are prone to rapid perioperative rise in serum sodium, which can be detrimental. The risk is lower than the benefit as these patients get new liver anyway!!

#tranplantation

#hepatology

#nephrology

#pharmacology

References:

1. Parekh A, Rajaram P, Patel G, Subramanian RM. Utility of Tolvaptan in the Perioperative Management of Severe Hyponatremia During Liver Transplantation: A Case Report. Transplant Proc. 2017 Dec;49(10):2399-2401. doi: 10.1016/j.transproceed.2017.09.011. PMID: 29198689.

2. Imai S, Shinoda M, Obara H, Kitago M, Hibi T, Abe Y, Yagi H, Matsubara K, Higashi H, Itano O, Kitagawa Y. Tolvaptan for Fluid Management in Living Donor Liver Transplant Recipients. Ann Transplant. 2018 Jan 9;23:25-33. doi: 10.12659/aot.905817. PMID: 29311539; PMCID: PMC6248066.