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Hyponatremia in cirrhosis and end-stage liver disease: treatment with the vasopressin V₂-receptor antagonist tolvaptan.

Gaglio P, Marfo K, Chiodo J - Dig. Dis. Sci. (2012)

Bottom Line: Hyponatremia is common in patients with cirrhosis and portal hypertension, and is characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance.The primary cause is increased release of arginine vasopressin.Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant.

View Article: PubMed Central - PubMed

Affiliation: Division of Hepatology, Montefiore Medical Center and Albert Einstein College of Medicine, 111 East 210th Street, Rosenthal 2 Red Zone, Bronx, NY 10467, USA. eric.justice@bioscicom.net

ABSTRACT
Hyponatremia is common in patients with cirrhosis and portal hypertension, and is characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance. The primary cause is increased release of arginine vasopressin. Hyponatremia is associated with increased mortality in cirrhotic patients, those with end-stage liver disease (ESLD) on transplant waiting lists, and, in some studies, posttransplantation patients. Clinical evidence suggests that adding serum sodium to model for ESLD (MELD) scoring identifies patients in greatest need of liver transplantation by improving waiting list mortality prediction. Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant. Vasopressin receptor antagonists, which act to increase free water excretion (aquaresis) and thereby increase serum sodium concentration, have been evaluated in patients with hypervolemic hyponatremia (including cirrhosis and heart failure) and euvolemic hyponatremia (SIADH). Tolvaptan, a selective vasopressin V(2)-receptor antagonist, is the only oral agent in this class approved for raising sodium levels in hypervolemic and euvolemic hyponatremia. The SALT trials showed that tolvaptan treatment rapidly and effectively resolved hyponatremia in these settings, including cirrhosis, and it has been shown that this agent can be safely and effectively used in long-term treatment. Fluid restriction should be avoided during the first 24 h of treatment to prevent overly rapid correction of hyponatremia, and tolvaptan should not be used in patients who cannot sense/respond to thirst, anuric patients, hypovolemic patients, and/or those requiring urgent intervention to raise serum sodium acutely.

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Relative risk of death (with 95 % confidence intervals [CI]) according to serum sodium concentration after adjustment for MELD score among 6,769 registrants in the Organ Procurement and Transplantation Network (2005 and 2006). From Kim et al. [4] reproduced with permission
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Fig2: Relative risk of death (with 95 % confidence intervals [CI]) according to serum sodium concentration after adjustment for MELD score among 6,769 registrants in the Organ Procurement and Transplantation Network (2005 and 2006). From Kim et al. [4] reproduced with permission

Mentions: Hyponatremia is associated with increased mortality in patients on the liver transplant waiting list. Data reported by Kim et al. [4] on 6,769 registrants in the Organ Procurement and Transplantation Network for 2005 and 2006 indicate that the serum sodium level and MELD score were significantly associated with mortality, with a hazard ratio of 1.21 per MELD point and 1.05 per 1-unit decrease in serum sodium level from 140 to 125 mEq/L (P < .001 for both). Decreases in serum sodium concentration were associated with an increased risk of death even after adjustment for MELD score (Fig. 2). The authors noted that a significant interaction between MELD score and serum sodium was observed, and that a revised MELD score utilizing a combination of the two factors in assigning transplantation priority might have resulted in avoidance of death in a sizable proportion of patients (see below for further discussion). In 296 patients referred for transplantation, Heuman et al. [20] found that MELD score, persistent ascites, and serum sodium level < 135 mEq/L were independent predictors of early mortality on multivariate analysis. MELD score was the sole independent predictor among patients with MELD scores > 21, whereas persistent ascites and low serum sodium were the only predictors among patients with MELD scores < 21; in the latter group of patients, serum sodium was an independent predictor whether analyzed as a continuous variable or as a categorical variable with a cutoff of 135 mEq/L.Fig. 2


Hyponatremia in cirrhosis and end-stage liver disease: treatment with the vasopressin V₂-receptor antagonist tolvaptan.

Gaglio P, Marfo K, Chiodo J - Dig. Dis. Sci. (2012)

Relative risk of death (with 95 % confidence intervals [CI]) according to serum sodium concentration after adjustment for MELD score among 6,769 registrants in the Organ Procurement and Transplantation Network (2005 and 2006). From Kim et al. [4] reproduced with permission
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3472061&req=5

Fig2: Relative risk of death (with 95 % confidence intervals [CI]) according to serum sodium concentration after adjustment for MELD score among 6,769 registrants in the Organ Procurement and Transplantation Network (2005 and 2006). From Kim et al. [4] reproduced with permission
Mentions: Hyponatremia is associated with increased mortality in patients on the liver transplant waiting list. Data reported by Kim et al. [4] on 6,769 registrants in the Organ Procurement and Transplantation Network for 2005 and 2006 indicate that the serum sodium level and MELD score were significantly associated with mortality, with a hazard ratio of 1.21 per MELD point and 1.05 per 1-unit decrease in serum sodium level from 140 to 125 mEq/L (P < .001 for both). Decreases in serum sodium concentration were associated with an increased risk of death even after adjustment for MELD score (Fig. 2). The authors noted that a significant interaction between MELD score and serum sodium was observed, and that a revised MELD score utilizing a combination of the two factors in assigning transplantation priority might have resulted in avoidance of death in a sizable proportion of patients (see below for further discussion). In 296 patients referred for transplantation, Heuman et al. [20] found that MELD score, persistent ascites, and serum sodium level < 135 mEq/L were independent predictors of early mortality on multivariate analysis. MELD score was the sole independent predictor among patients with MELD scores > 21, whereas persistent ascites and low serum sodium were the only predictors among patients with MELD scores < 21; in the latter group of patients, serum sodium was an independent predictor whether analyzed as a continuous variable or as a categorical variable with a cutoff of 135 mEq/L.Fig. 2

Bottom Line: Hyponatremia is common in patients with cirrhosis and portal hypertension, and is characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance.The primary cause is increased release of arginine vasopressin.Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant.

View Article: PubMed Central - PubMed

Affiliation: Division of Hepatology, Montefiore Medical Center and Albert Einstein College of Medicine, 111 East 210th Street, Rosenthal 2 Red Zone, Bronx, NY 10467, USA. eric.justice@bioscicom.net

ABSTRACT
Hyponatremia is common in patients with cirrhosis and portal hypertension, and is characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance. The primary cause is increased release of arginine vasopressin. Hyponatremia is associated with increased mortality in cirrhotic patients, those with end-stage liver disease (ESLD) on transplant waiting lists, and, in some studies, posttransplantation patients. Clinical evidence suggests that adding serum sodium to model for ESLD (MELD) scoring identifies patients in greatest need of liver transplantation by improving waiting list mortality prediction. Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant. Vasopressin receptor antagonists, which act to increase free water excretion (aquaresis) and thereby increase serum sodium concentration, have been evaluated in patients with hypervolemic hyponatremia (including cirrhosis and heart failure) and euvolemic hyponatremia (SIADH). Tolvaptan, a selective vasopressin V(2)-receptor antagonist, is the only oral agent in this class approved for raising sodium levels in hypervolemic and euvolemic hyponatremia. The SALT trials showed that tolvaptan treatment rapidly and effectively resolved hyponatremia in these settings, including cirrhosis, and it has been shown that this agent can be safely and effectively used in long-term treatment. Fluid restriction should be avoided during the first 24 h of treatment to prevent overly rapid correction of hyponatremia, and tolvaptan should not be used in patients who cannot sense/respond to thirst, anuric patients, hypovolemic patients, and/or those requiring urgent intervention to raise serum sodium acutely.

Show MeSH
Related in: MedlinePlus