Skip to main content
SpringerLink
Log in

The Changing Role of Sodium Management in Cirrhosis

  • Liver (J Bajaj, Section Editor)
  • Published:
Current Treatment Options in Gastroenterology Aims and scope Submit manuscript

Opinion Statement

Hyponatremia may occur in patients with cirrhosis and ascites mainly due to water retention and an inability of the kidney to excrete free water. The main reason for this abnormality is related to the fact that these patients have portal hypertension and this leads to systemic vasodilation that in turn activates sodium-retaining and water-retaining systems such as the renin-angiotensin-aldosterone system and arginine vasopressin (AVP). AVP increases solute-free water retention by acting on the V2 receptors of the kidney-collecting tubes. Hyponatremia in cirrhosis is defined as a serum sodium level less than 130 meq/L. The appearance of hyponatremia in patients with advanced cirrhosis portends a poor prognosis before and after liver transplantation. Treatment of hyponatremia is difficult; fluid restriction rarely increases serum sodium levels and other therapies are associated with important drawbacks. A thorough discussion of the underlying mechanisms leading to hyponatremia and hypernatremia in cirrhosis and current treatment options including the use of vaptans (V2 receptor antagonists) are discussed in this review.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently have been highlighted as: • Of importance •• Of major importance

  1. Angeli P et al. Hyponatremia in cirrhosis: results of a patient population survey. Hepatology. 2006;44(6):1535–42.

    Article  CAS  PubMed  Google Scholar 

  2. Gines P et al. Hyponatremia in cirrhosis: from pathogenesis to treatment. Hepatology. 1998;28(3):851–64.

    Article  CAS  PubMed  Google Scholar 

  3. Adrogue HJ, Madias NE. Diagnosis and treatment of hyponatremia. Am J Kidney Dis. 2014;64(5):681–4.

    Article  PubMed  Google Scholar 

  4. Gines P, Guevara M. Hyponatremia in cirrhosis: pathogenesis, clinical significance, and management. Hepatology. 2008;48(3):1002–10.

    Article  CAS  PubMed  Google Scholar 

  5. John S, Thuluvath PJ. Hyponatremia in cirrhosis: pathophysiology and management. World J Gastroenterol. 2015;21(11):3197–205.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Biggins SW et al. Serum sodium predicts mortality in patients listed for liver transplantation. Hepatology. 2005;41(1):32–9.

    Article  CAS  PubMed  Google Scholar 

  7. Gines A et al. Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterology. 1993;105(1):229–36.

    CAS  PubMed  Google Scholar 

  8. Sola E et al. Factors related to quality of life in patients with cirrhosis and ascites: relevance of serum sodium concentration and leg edema. J Hepatol. 2012;57(6):1199–206.

    Article  CAS  PubMed  Google Scholar 

  9. Yun BC et al. Impact of pretransplant hyponatremia on outcome following liver transplantation. Hepatology. 2009;49(5):1610–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Londono MC et al. Hyponatremia impairs early posttransplantation outcome in patients with cirrhosis undergoing liver transplantation. Gastroenterology. 2006;130(4):1135–43.

    Article  PubMed  Google Scholar 

  11. Heuman DM et al. Persistent ascites and low serum sodium identify patients with cirrhosis and low MELD scores who are at high risk for early death. Hepatology. 2004;40(4):802–10.

    Article  PubMed  Google Scholar 

  12. Kim WR et al. Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med. 2008;359(10):1018–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Biggins SW et al. Evidence-based incorporation of serum sodium concentration into MELD. Gastroenterology. 2006;130(6):1652–60.

    Article  PubMed  Google Scholar 

  14. Ruf AE et al. Addition of serum sodium into the MELD score predicts waiting list mortality better than MELD alone. Liver Transpl. 2005;11(3):336–43.

    Article  PubMed  Google Scholar 

  15. Fernandez-Seara J et al. Systemic and regional hemodynamics in patients with liver cirrhosis and ascites with and without functional renal failure. Gastroenterology. 1989;97(5):1304–12.

    CAS  PubMed  Google Scholar 

  16. Esteva-Font C et al. Aquaporin-1 and aquaporin-2 urinary excretion in cirrhosis: relationship with ascites and hepatorenal syndrome. Hepatology. 2006;44(6):1555–63.

    Article  CAS  PubMed  Google Scholar 

  17. Maroto A et al. Brachial and femoral artery blood flow in cirrhosis: relationship to kidney dysfunction. Hepatology. 1993;17(5):788–93.

    CAS  PubMed  Google Scholar 

  18. Vallance P, Moncada S. Hyperdynamic circulation in cirrhosis: a role for nitric oxide? Lancet. 1991;337(8744):776–8.

    Article  CAS  PubMed  Google Scholar 

  19. Schrier RW. Water and sodium retention in edematous disorders: role of vasopressin and aldosterone. Am J Med. 2006;119(7 Suppl 1):S47–53.

    Article  CAS  PubMed  Google Scholar 

  20. Gines P, Cardenas A. The management of ascites and hyponatremia in cirrhosis. Semin Liver Dis. 2008;28(1):43–58.

    Article  CAS  PubMed  Google Scholar 

  21. Iwakiri Y. The molecules: mechanisms of arterial vasodilatation observed in the splanchnic and systemic circulation in portal hypertension. J Clin Gastroenterol. 2007;41 Suppl 3:S288–94.

    Article  CAS  PubMed  Google Scholar 

  22. Thibonnier M et al. Molecular pharmacology of human vasopressin receptors. Adv Exp Med Biol. 1998;449:251–76.

    Article  CAS  PubMed  Google Scholar 

  23. Kwon TH et al. Physiology and pathophysiology of renal aquaporins. Semin Nephrol. 2001;21(3):231–8.

    Article  CAS  PubMed  Google Scholar 

  24. Nielsen S et al. Aquaporins in the kidney: from molecules to medicine. Physiol Rev. 2002;82(1):205–44.

    Article  CAS  PubMed  Google Scholar 

  25. Sterns RH, Riggs JE, Schochet Jr SS. Osmotic demyelination syndrome following correction of hyponatremia. N Engl J Med. 1986;314(24):1535–42.

    Article  CAS  PubMed  Google Scholar 

  26. Tanneau RS et al. High incidence of neurologic complications following rapid correction of severe hyponatremia in polydipsic patients. J Clin Psychiatry. 1994;55(8):349–54.

    CAS  PubMed  Google Scholar 

  27. Guevara M et al. Hyponatremia is a risk factor of hepatic encephalopathy in patients with cirrhosis: a prospective study with time-dependent analysis. Am J Gastroenterol. 2009;104(6):1382–9.

    Article  PubMed  Google Scholar 

  28. Riggio O et al. Incidence, natural history, and risk factors of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt with polytetrafluoroethylene-covered stent grafts. Am J Gastroenterol. 2008;103(11):2738–46.

    Article  PubMed  Google Scholar 

  29. Guevara M et al. Risk factors for hepatic encephalopathy in patients with cirrhosis and refractory ascites: relevance of serum sodium concentration. Liver Int. 2010;30(8):1137–42.

    Article  CAS  PubMed  Google Scholar 

  30. Schwabl P et al. Risk factors for development of spontaneous bacterial peritonitis and subsequent mortality in cirrhotic patients with ascites. Liver Int. 2015;35(9):2121–8. Retrospective cohort study demonstrating that hyponatremia along with Child-Pugh stage C and elevated ascites represent predictive factors for SBP development and higher mortality in patients with liver cirrhosis.

    Article  PubMed  Google Scholar 

  31. Rimola A et al. Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document. Int Ascites Club J Hepatol. 2000;32(1):142–53.

    CAS  Google Scholar 

  32. Arvaniti V et al. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterology. 2010;139(4):1246–56. 1256.e1–5.

    Article  PubMed  Google Scholar 

  33. European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010;53(3): 397–417.

  34. Cordoba J, Blei AT. Brain edema and hepatic encephalopathy. Semin Liver Dis. 1996;16(3):271–80.

    Article  CAS  PubMed  Google Scholar 

  35. Blei AT, Larsen FS. Pathophysiology of cerebral edema in fulminant hepatic failure. J Hepatol. 1999;31(4):771–6.

    Article  CAS  PubMed  Google Scholar 

  36. Haussinger D et al. Hepatic encephalopathy in chronic liver disease: a clinical manifestation of astrocyte swelling and low-grade cerebral edema? J Hepatol. 2000;32(6):1035–8.

    Article  CAS  PubMed  Google Scholar 

  37. Butterworth RF. Pathogenesis of hepatic encephalopathy: new insights from neuroimaging and molecular studies. J Hepatol. 2003;39(2):278–85.

  38. Videen JS et al. Human cerebral osmolytes during chronic hyponatremia. A proton magnetic resonance spectroscopy study. J Clin Invest. 1995;95(2):788–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Soupart A et al. Rapid (24-hour) reaccumulation of brain organic osmolytes (particularly myo-inositol) in azotemic rats after correction of chronic hyponatremia. J Am Soc Nephrol. 2002;13(6):1433–41.

    Article  CAS  PubMed  Google Scholar 

  40. Laubenberger J et al. Proton magnetic resonance spectroscopy of the brain in symptomatic and asymptomatic patients with liver cirrhosis. Gastroenterology. 1997;112(5):1610–6.

    Article  CAS  PubMed  Google Scholar 

  41. Restuccia T et al. Effects of dilutional hyponatremia on brain organic osmolytes and water content in patients with cirrhosis. Hepatology. 2004;39(6):1613–22.

    Article  CAS  PubMed  Google Scholar 

  42. Furst H et al. The urine/plasma electrolyte ratio: a predictive guide to water restriction. Am J Med Sci. 2000;319(4):240–4.

    Article  CAS  PubMed  Google Scholar 

  43. McCormick PA et al. Intravenous albumin infusion is an effective therapy for hyponatraemia in cirrhotic patients with ascites. Gut. 1990;31(2):204–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Abbasoglu O et al. Liver transplantation in hyponatremic patients with emphasis on central pontine myelinolysis. Clin Transpl. 1998;12(3):263–9.

    CAS  Google Scholar 

  45. Decaux G, Soupart A, Vassart G. Non-peptide arginine-vasopressin antagonists: the vaptans. Lancet. 2008;371(9624):1624–32.

    Article  CAS  PubMed  Google Scholar 

  46. Wong F et al. A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration in patients with hyponatremia: a multicenter, randomized, placebo-controlled trial. Hepatology. 2003;37(1):182–91.

    Article  CAS  PubMed  Google Scholar 

  47. Gerbes AL et al. Therapy of hyponatremia in cirrhosis with a vasopressin receptor antagonist: a randomized double-blind multicenter trial. Gastroenterology. 2003;124(4):933–9.

    Article  CAS  PubMed  Google Scholar 

  48. Schrier RW et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355(20):2099–112.

    Article  CAS  PubMed  Google Scholar 

  49. Gines P et al. Effects of satavaptan, a selective vasopressin V(2) receptor antagonist, on ascites and serum sodium in cirrhosis with hyponatremia: a randomized trial. Hepatology. 2008;48(1):204–13.

    Article  CAS  PubMed  Google Scholar 

  50. Cardenas A et al. Tolvaptan, an oral vasopressin antagonist, in the treatment of hyponatremia in cirrhosis. J Hepatol. 2012;56(3):571–8. Sub-analysis of the Study of Ascending Levels of Tolvaptan trials, comparing tolvaptan treatment against placebo exclusively in cirrhotic patients with hyponatremia. The results demonstrated that tolvaptan in addition to standard therapy, effectively raises and maintains serum sodium concentrations and improves health-related quality of life.

    Article  CAS  PubMed  Google Scholar 

  51. O’Leary JG, Davis GL. Conivaptan increases serum sodium in hyponatremic patients with end-stage liver disease. Liver Transpl. 2009;15(10):1325–9.

    Article  PubMed  Google Scholar 

  52. Torres VE, Chapman AB, Devuyst O, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012;367:2407–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Samsca (Tolvaptan): Drug safety communication—FDA limits duration and usage due to possible liver injury leading to organ transplant or death. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm350185.htm.

  54. Cárdenas A, Riggio O. Correction of hyponatraemia in cirrhosis: treating more than a number! J Hepatol. 2015;62(1):13–4.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, St. Elizabeth Medical Center, Brighton, MA, USA

    Blanca Lizaola MD

  2. Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Alan Bonder MD & Elliot B. Tapper MD

  3. GI/Liver Unit, Institute of Digestive Diseases and Metabolism, University of Barcelona, Hospital Clinic-Villarroel 170, Esc 3-2, 08036, Barcelona, Spain

    Angela Mendez-Bocanegra MD & Andres Cardenas MD, MMSc, PhD, AGAF, FAASLD

Authors
  1. Blanca Lizaola MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alan Bonder MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elliot B. Tapper MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Angela Mendez-Bocanegra MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andres Cardenas MD, MMSc, PhD, AGAF, FAASLD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andres Cardenas MD, MMSc, PhD, AGAF, FAASLD.

Ethics declarations

Conflict of Interest

Blanca Lizaola declares that she has no conflict of interest. Alan Bonder declares that he has no conflict of interest. Elliot B. Tapper declares that he has no conflict of interest. Angela Mendez-Bocanegra declares that she has no conflict of interest. Andres Cardenas declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Liver

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lizaola, B., Bonder, A., Tapper, E.B. et al. The Changing Role of Sodium Management in Cirrhosis. Curr Treat Options Gastro 14, 274–284 (2016). https://doi.org/10.1007/s11938-016-0094-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11938-016-0094-y

Keywords

Search

Navigation