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2007, Number 4

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Ann Hepatol 2007; 6 (4)

Pathophysiology of ascites and dilutional hyponatremia: Contemporary use of aquaretic agents

García LJ, Martínez SJ, Estradas J, Torre A, Uribe M

Language: English
References: 41
Page: 214-221
PDF size: 185.07 Kb.


Text Extraction

Ascites, the most common complication of cirrhosis, is associated with a poor quality of life, an increased risk of infection, and renal failure. Twenty percent of cirrhotic patients have ascites at the time of diagnosis, while 30% and 50% will develop ascites by 5 and 10 years, respectively. There are several factors that contribute to ascites formation in cirrhotic patients, these include splanchnic vasodilatation, arterial hypotension, high cardiac output, and decreased vascular resistance. These factors lead to ineffective intravascular volume (hyperdynamic state), impairment of renal function, and subsequent water and sodium retention, all of which lead to dilutional hyponatremia (serum sodium ‹130 mEq/L), one of the most important prognostic factors in these patients. In conclusion, the therapeutic objective is to improve sodium balance and circulatory function through non-pharmacological measures, such as dietary sodium and water restriction as well as bed rest. Spironolactone (100-400 mg/day) is the initial drug of choice, while loop diuretics (like furosemide, 40-60 mg/day) are frequently used as adjuvants. Recently, agents that interfere with the renal effects of vasopressin by inhibiting water reabsorption in collecting ducts and producing free water diuresis have been used. These agents are called aquaretics and can be useful in the treatment of ascites unresponsive to conventional therapy.


REFERENCES

  1. Runyon BA. Care of patients with ascites. N Engl J Med 1994; 330: 337-342.

  2. Runyon BA. Management of adult patients with ascites due to cirrhosis. Hepatology 2004; 39: 841-854.

  3. Gines P, Beri T, Bernardi M, Bichet DG, Hamon G, Jimenez W, et al. Hyponatremia in cirrhosis: from pathogenesis to treatment. Hepatology 1998; 28: 851-861.

  4. Arroyo V. Pathophysiology, diagnosis and treatment of ascites in cirrhosis. Ann Hepatol 2002; 2: 72-79.

  5. Arroyo V, Colmenero J. Ascites and hepatorenal syndrome in cirrhosis: pathophysiology basis of therapy and current management. J Hepatol 2003; 38: S69-S89.

  6. Gines P, Cardenas A, Arroyo V, Rodes J. Management of cirrhosis and ascites. N Engl J Med 2004; 350: 1646-1654.

  7. Lieberman FL, Ito S, Reynolds TB. Effective plasma volume in cirrhosis with ascites. Evidence that a decreased value does not account for renal sodium retention, a sponteneous reduction in glomerular filtration rate (GFR), and a fall in GFR during drug-induced diuresis. J Clin Invest 1969; 48: 975-81.

  8. Gentilini P, Laffi G, La Villa G, Romanelli RG, Blendis LM. Ascites and hepatorenal syndrome in cirrhosis: two entities or the continuation of the same complication? J Hepatol 1999; 31: 1088-1097.

  9. Henriksen JH. Ascites and hepatorenal syndrome: recent advances in pathogenesis. J Hepatol 1995; 23(Supp 1): 25-30.

  10. Schrier RW, Arroyo V, Bernardi M, Epstein M, Henriksen JH, Rodes J. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology 1988; 8(5): 1151-7.

  11. Peña JC. Mecanismos renales y extrarenales en la retención de sodio y agua en la cirrosis con ascitis. Rev Invest Clin 1995; 47: 63-79.

  12. Rivera A, Peña JC, Barcena C, Rangel S, Dies F. Renal excretion of water, sodium and potassium in cirrhosis of the liver. Metabolism 1961; 10: 1-17.

  13. Henriksen JH. Ascites and hepatorenal syndrome: recent advances in pathogenesis. J Hepatol 1995; 23(Supp 1): 25-30.

  14. Aiza I, Perez GO, Schiff ER. Management of ascites in patients with chronic liver disease. Am J Gastroenterol 1994; 89: 1949-1955.

  15. Arroyo V, Gines P. Mechanism of sodium retention and ascites formation in cirrhosis. J Hepatol 1993; 17(suppl 2): S24-S28.

  16. Arroyo V, Claria J, Salo J. Antidiuretic hormona and the pathogenesis of water retention in cirrosis with ascites. Sem Liver Dis 1994; 14: 44-58.

  17. Boyer TD. Aquaretics in cirrhotics with hyponatremia. J Gastroenterol Hepatol 2004; 19: S191-S193.

  18. Moore KP, Wong F, Gines P, Bernardi M, Ochs A, Salerno F, et al. The management of ascites in cirrhosis: report on the consensus conference of the international ascites club. Hepatology 2003; 38: 258-266.

  19. Brater DC. Diuretic therapy. N Engl J Med 1998; 339: 387-395.

  20. Gines P, Arroyo V. Paracentesis in the management of cirrhotic ascites. J Hepatol 1993; 17(suppl 2): S14-S18.

  21. Arroyo V. Albumin in the treatment of liver disease – new features of a classical treatment. Aliment Pharmacol Ther 2002; 16 (suppl 5): 1-5.

  22. Torre Delgadillo A. Ascitis refractaria e hiponatremia dilucional: tratamiento actual y nuevos acuaréticos: Rev Gastroenterol Mex. 2005; 70(3): 299-311.

  23. Nejsum LN. The renal plumbing system: aquaporin water channels. Cell Mol Life Sci 2005; 62: 1692-1706.

  24. Preston GM, Carroll TP, Guggino WB, Agre P. Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein. Science 1992; 256: 385-387.

  25. Nejsum LN. The renal plumbing system: aquaporin water channels. Cell Mol Life Sci 2005; 62: 1692-1706.

  26. Fernandez-Llama P, Turner R, Dibona G, Knepper MA. Renal expression of aquaporins in liver cirrhosis induced by chronic common bile duct ligation in rats. J Am Soc Nephrol 1999; 10: 1950-7.

  27. Fernandez-Llama P, Jimenez W, Bosch-Marce M, Arroyo V, Nielsen S, Knepper MA. Dysregulation of renal aquaporins and Na-Cl cotransporter in CCl4-induced cirrhosis. Kidney Int 2000; 58: 216-28.

  28. Tajika Y, Matsuzaki T, Suzuki T, Aoki T, Hagiwara H, Kuwahara M, et al. Aquaporin-2 is retrieved to the apical storage compartment via early endosomes and phosphatidylinositol 3-kinase-dependent pathway. Endocrinology 2004; 145: 4375-4383.

  29. Yamamoto T, Sasaki S, Fushimi K, Kawasaki K, Yaoita E, Oota K, et al. Localization and expression of a collecting duct water channel, aquaporin, in hydrated and dehydrated rats. J Exp Nephrol 1995; 3: 193-201.

  30. Gines P, Jimenez W. Aquaretic agents: a new potential treatment of dilutional hyponatremia in cirrhosis. J Hepatol 1996; 24: 506-512.

  31. Gadano A, Moreau R, Pessione F, Trombino C, Giuily N, Sinnassamy P, Valla D, Lebrec D. Aquaretic effects of niravoline, a k-opioid agonist, in patients with cirrhosis. Journal of Hepatology 2000; 32: 3842.

  32. Udelson JE, Smith WB, Hendrix GH, et al. Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure. Circulation 2001; 104: 2417-2423.

  33. Thibonnier M, Kilani A, Rahman M, et al. Effects of the nonpeptide V(1) vasopressin receptor antagonist SR49059 in hypertensive patients. Hypertension 1999: 34: 1293-1300.

  34. Ferguson JW, Therapondos G, Newby DE, Hayes PC. Therapeutic role of vasopressin receptor antagonism in patients with liver cirrhosis. Clin Sci (Lond) 2003; 105: 1-8.

  35. Chan PS, Coupet J, Park HC, Lai F, Hartupee D, Cervoni P, Dusza JP, et al. VPA-985, a nonpeptide orally active and selective vasopressin V2 receptor antagonist. Adv Exp Med Biol 1998; 449: 439-443.

  36. Wong F, Blei, AT, Blendis LM, Thuluvath PJ. A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration in patients with hyponatremia: A multicenter, randomized, placebo-controlled trial. Hepatology 2003; 37: 182-191.

  37. Inoue T, Ohnishi A, Matsuo A, Kawai B, Kunihiro N, Tada Y, Koizumi F, Chau T, Okada K, Yamamura Y, Tanaka T. Therapeutic and diagnostic potential of a vasopressin-2 antagonist for impaired water handling in cirrhosis. Clin Pharmacol Ther 1998; 63: 561-70.

  38. Guyader D, Patat A, Ellis-Grosse EJ, Orczyk GP. Pharmacodynamic effects of a nonpeptide antidiuretic hormone V2 antagonist in cirrhotic patients with ascites. Hepatology 2002; 36: 1197-1205.

  39. Patat A, Ellis-Grosse EJ, Orczyk GP, Gandon JM. Pharmacodynamic effects of a novel, non-peptide, V2 receptor antagonist, VPA-985, given with hydrochlorothiazide. Clin Pharmacol Ther 2000; 67: 110.

  40. Swan SK, Lambvrecht LJ, Orczyk GP, Ellis-Grosse EJ. Interaction between VPA-985, an ADH (V2) antagonist, and furosemide. J Am Soc Nephrol 1999; 10: 124A.

  41. Afdhal N, Andres Cardenas A, Gines P, Gross P, Verbalis J, Berl T, Schrier R, Bichet D, Wagoner L, Ouyang J. Randomized, placebo-controlled trial of tolvaptan, a novel v2-receptor antagonist, in hyponatremia: results of the salt 2 trial with emphasis on efficacy and safety in cirrhosis. Hepatology 2005; 42(S1): 756A.




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