Evidence-based hyponatremia management in liver disease

Abstract

Hyponatremia is primarily a water balance disorder associated with high morbidity and mortality. The pathophysiological mechanisms behind hyponatremia are multifactorial, and diagnosing and treating this disorder remains challenging. In this review, the classification, pathogenesis, and step-by-step management approaches for hyponatremia in patients with liver disease are described based on recent evidence. We summarize the five sequential steps of the traditional diagnostic approach: 1) confirm true hypotonic hyponatremia, 2) assess the severity of hyponatremia symptoms, 3) measure urine osmolality, 4) classify hyponatremia based on the urine sodium concentration and extracellular fluid status, and 5) rule out any coexisting endocrine disorder and renal failure. Distinct treatment strategies for hyponatremia in liver disease should be applied according to the symptoms, duration, and etiology of disease. Symptomatic hyponatremia requires immediate correction with 3% saline. Asymptomatic chronic hyponatremia in liver disease is prevalent and treatment plans should be individualized based on diagnosis. Treatment options for correcting hyponatremia in advanced liver disease may include water restriction; hypokalemia correction; and administration of vasopressin antagonists, albumin, and 3% saline. Safety concerns for patients with liver disease include a higher risk of osmotic demyelination syndrome.

Keywords: Hyponatremia; Liver cirrhosis; Liver disease; Water-electrolyte imbalance.

Figure 1.

Pathogenesis of hypervolemic hyponatremia in patients with liver cirrhosis. ADH, antidiuretic hormone; DNA, deoxyribonucleic acid; NO, nitric oxide; PG, prostaglandin; RES, reticuloendothelial system.

Figure 2.

Hyponatremia diagnostic approach in patients with liver disease. CHF, congestive heart failure; GI, gastrointestinal; LVP, large volume paracentesis; SIAD, syndrome of inappropriate antidiuresis.

Figure 3.

Treatment of hyponatremia in patients with liver disease. GCS, Glasgow Coma Scale; OLT, orthotopic liver transplant; sNa, serum sodium concentration. ^*Acute, If the hyponatremia has developed over a period of less than 48 hours. ^†Chronic, If the hyponatremia has been present for 48 hours or more or if the duration is unknown.

Figure 4.

Mechanism of action of vaptan. ADH, antidiuretic hormone; AQP2, aquaporin-2; AQP3, aquaporin-3; AQP4, aquaporin-4.

Figure 5.

Results of hyponatremia treatment in liver disease. (A) Flowchart of selection of studies on the effect of tolvaptan treatment on hyponatremia. (B) Forest plot showing the effect of tolvaptan treatment on hyponatremia (change from baseline hyponatremia [mmol/L]). (C) Flowchart of selection of studies on the effect of albumin treatment on hyponatremia. (D) Forest plot showing the effect of albumin treatment on hyponatremia (improvement in hyponatremia [%]).

Figure 6.

Management of a patient with hyponatremia and end-stage liver disease (ESLD) for liver transplantation (LT) (Figure modified from Praharaj and Anand. J Clin Exp Hepatol 2022;12:575-594) [129].