The Role of Arachidonic Acid Metabolites in the Functional Renal Impairment Associated with Liver Disease

  • Robert D. Zipser
  • Timothy Little
  • Hector Ziperovich
  • Robert Duke


There are many morphologic and functional abnormalities of the kidney associated with liver disease. Both organs may be simultaneously affected by toxic agents such as carbon tetrachloride, by infections such as leptospirosis or generalized sepsis, and by metabolic changes such as hypoxia or shock. In addition, there are several well-described glomerulonephropathies such as those associated with hepatitis B infection, tubular abnormalities including renal tubular acidosis in chronic liver disease, and several genetic and neoplastic diseases. Among the more enigmatic associations are the functional changes in renal hemodynamics and sodium and water excretion that occur during the course of severe liver disease.1 These abnormalities are considered functional because anatomic changes have not been identified and because renal function is normal on successful transplantation to an unaffected recipient.2 In their most extreme phase the functional abnormalities progress to renal failure (hepatorenal syndrome) characterized by oliguria, intense sodium retention, and extensive vasoconstriction of the outer segments of the renal cortex.3 Although a number of liver disorders may be associated with renal failure, it is most common in patients with cirrhosis and ascites. Because of the functional nature of the renal impairment, there have been many studies of different vasoactive systems in patients with cirrhosis and ascites.


Renal Blood Flow Sodium Retention Severe Liver Disease Hepatorenal Syndrome Arachidonic Acid Metabolite 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Epstein M (ed): The Kidney in Liver Disease. New York, Elsevier North-Holland, 1978.Google Scholar
  2. 2.
    Koppel MH, Coburn JW, Mims MM, et al: Transplantation of cadaveric kidneys from patients with hepatorenal syndrome. Evidence for the functional nature of renal failure in advanced liver disease. N Engl J Med 25: 1367–1371, 1969.CrossRefGoogle Scholar
  3. 3.
    Conn HO: A rational approach to the hepatorenal syndrome. Gastroenterology 65: 321–340, 1973.PubMedGoogle Scholar
  4. 4.
    Bongiovanni AM, Eisenmenger WJ: Adrenal cortical metabolism in chronic liver disease. J Clin Endocrinol Metab 11:152–172, 1951.PubMedCrossRefGoogle Scholar
  5. 5.
    Arroyo V, Bosch J, Gaya-Beltran J, et al: Plasma renin activity and urinary sodium excretion as prognostic indicators in nonazotemic cirrhosis with ascites. Ann Intern Med 94: 198–201, 1981.PubMedGoogle Scholar
  6. 6.
    Epstein M: Deranged sodium homeostasis in cirrhosis. Gastroenterology 76: 622–635, 1979.PubMedGoogle Scholar
  7. 7.
    Verberkmoes R, Clemens J, Michielsen P, et al: Bartter’s syndrome with hyperplasia of renomedullary interstitial cells. Successful treatment with indomethacin. Kidney Int 9: 302–307, 1976.CrossRefGoogle Scholar
  8. 8.
    Fichman M, Telfer N, Zia P, et al: Role of prostaglandins in the pathogenesis of Bartter’s syndrome. Am J Med 60: 785–797, 1976.PubMedCrossRefGoogle Scholar
  9. 9.
    Boyer TD, Reynolds TB: Prostaglandin insufficiency: A role in the hepatorenal syndrome. Gastroenterology 71: 899, 1976.Google Scholar
  10. 10.
    Horton R, Zipser RD, Fichman M: Prostaglandins, renal function and vascular regulation. Med Clin North Am 65: 891–914, 1981.PubMedGoogle Scholar
  11. 11.
    Gill JR Jr, Frolich JC, Bowden RE et al: Bartter’s syndrome: A disorder characterized by high urinary prostaglandins and a dependence of hypereninemia on prostaglandin synthesis. Am J Med 61: 43–51, 1976.PubMedCrossRefGoogle Scholar
  12. 12.
    Boyer TD, Zia P, Reynolds TB: Effect of indomethacin and prostaglandin Al on renal function and plasma renin activity in alcoholic liver disease. Gastroenterology 77: 215–222, 1979.PubMedGoogle Scholar
  13. 13.
    Zipser RD, JC Hoefs, PF Speckart, et al: Prostaglandins: Modulators of renal function and pressor resistance in chronic liver disease. J Clin Endocrinol Metab 48: 895–900, 1979.PubMedCrossRefGoogle Scholar
  14. 14.
    Donker AIM, Arisz L, Brentjens JRH, et al: The effects of indomethacin on kidney function and plasma renin activity in man. Nephron 17: 288–296, 1976.PubMedCrossRefGoogle Scholar
  15. 15.
    Speckart P, Zia P, Zipser R, et al: The effect of sodium restriction and prostaglandin inhibition on the renin-angiotensin system in man. J Clin Endocrinol Metab 44: 832–837, 1977.PubMedCrossRefGoogle Scholar
  16. 16.
    Dunn MJ, Zambraski EJ: Renal effects of drugs that inhibit prostaglandin synthesis. Kidney Int 18: 609–622, 1980.PubMedCrossRefGoogle Scholar
  17. 17.
    Swain JA, Heyndrickx GR, Boettcher DH, et al: Prostaglandin control of renal circulation in the unanesthetized dog and baboon. Am J Physiol 229: 826–830, 1975.PubMedGoogle Scholar
  18. 18.
    Kirshenbaum MA, White M, Stein HI, et al: Redistribution of renal cortical blood flow during inhibition of prostaglandin synthesis. Am J Physiol 227: 801–805, 1974.Google Scholar
  19. 19.
    Henrich WL, Anderson RJ, Berns Ai, et al: The role of renal nerves and prostaglandins in control of renal hemodynamics and plasma renin activity during hypotensive hemorrhage in the dog. J Clin Invest 61: 744–750, 1978.PubMedCrossRefGoogle Scholar
  20. 20.
    Epstein M, Berk DP, Hollenberg NK, et al: Renal failure in patients with cirrhosis: The role of active vasoconstriction. Am J Med 49: 175–185, 1970.PubMedCrossRefGoogle Scholar
  21. 21.
    Schroeder ET, Shear L, Sancetta SM, et al: Renal failure in patients with cirrhosis of the liver. Ill. Evaluation of intrarenal blood flow by paraaminohippurate extraction and response to angiotensin. Am J Med 43: 887–896, 1967.PubMedCrossRefGoogle Scholar
  22. 22.
    Wilkinson P, Bernardi M, Smith I, et al: Effect of beta-adrenergic blocking drugs on the renin-aldosterone system, sodium excretion, and renal hemodynamics in cirrhosis with ascites. Gastroenterology 73: 659–663, 1977.PubMedGoogle Scholar
  23. 23.
    Schroeder ET, Anderson GH, Goldman SH, et al: Effect of blockade of angiotensin II on blood pressure, renin and aldosterone in cirrhosis. Kidney Int 9: 511–519, 1976.PubMedCrossRefGoogle Scholar
  24. 24.
    Mirouze D, Reynolds T: Indomethacin inhibits diuretic action in patients with chronic liver disease and ascites. Gastroenterology 77: 28, 1979.Google Scholar
  25. 25.
    Tweeddale MG, Ogilvie RI: Antagonism of spironolactone-induced natriuresis by aspirin in man. N Engl J Med 289: 198–200, 1973.PubMedCrossRefGoogle Scholar
  26. 26.
    Speckart PF, Zia PK, Zipser RD, et al: The effect of prostaglandin inhibition on the renin and aldosterone response to posture in normal and hypertensive man. J Min Elec Metab 1: 208–215, 1978.Google Scholar
  27. 27.
    Martin K, Zipser RD, Horton R: The effects of prostaglandin inhibition on the hypertensive action of sodium retaining steroids. Hypertension 3: 622–628, 1981.PubMedGoogle Scholar
  28. 28.
    Laragh JH, Cannon PJ, Betzel CJ, et al: Angiotensin II, norepinephrine, and renal transport of electrolytes and water in normal man and in cirrhosis with ascites. J Clin Invest 42: 1179–1192, 1963.PubMedCrossRefGoogle Scholar
  29. 29.
    Arieff AI, Chidsey CC: Renal function in cirrhosis and the effects of prostaglandin Al. Am J Med 56: 695–703, 1974.PubMedCrossRefGoogle Scholar
  30. 30.
    Fichman MP, Littenberg G, Brooker G, et al: Effect of prostaglandin Al on renal and adrenal function in man. Circ Res 30–31 (Suppl II): 19–35, 1972.Google Scholar
  31. 31.
    Zusman RM, Axelrod L, Tolkoff-Rubin N: The treatment of the hepatorenal syndrome with intra-arterial administration of prostaglandin El. Prostaglandins 13: 819–830, 1977.PubMedCrossRefGoogle Scholar
  32. 32.
    Zipser R, Hoefs J, Speckart P, et al: Evidence for a critical role of prostaglandins in renin release, vascular reactivity and renal function in liver disease. Clin Res 25: 305A, 1977.Google Scholar
  33. 33.
    Gentilini P, Laffi G, Buzzelli, et al: Functional renal alterations in chronic liver diseases. Digestion 20: 73–78, 1980.PubMedCrossRefGoogle Scholar
  34. 34.
    Golub M, Zia P, Matsuno M, et al: Metabolism of prostaglandin Al and E1 in man. J Clin Invest 56: 1404–1410, 1975.PubMedCrossRefGoogle Scholar
  35. 35.
    Zipser RD, Kerlin P, Hoefs JC, et al: Renal kallikrein excretion in alcoholic cirrhosis: Relationship to other vasoactive systems. Am J Gastroenterol 75: 183–187, 1981.PubMedGoogle Scholar
  36. 36.
    Wernze H, Muller G, Goerig M: Relationship between urinary prostaglandin (PGE2 and PGF2a) and sodium excretion in various stages of chronic liver disease, in Samuelsson B, Ramwell PW, Paoletti R (eds): Advances in Prostaglandins and Thromboxane Research. New York, Raven Press, 1980, vol 7, p 1089.Google Scholar
  37. 37.
    Zia PK, Zipser RD, Speckart PF, et al: The measurement of urinary prostaglandin E in human subjects and in high renin states. J Clin Lab Med 92: 413–422. 1978.Google Scholar
  38. 38.
    Zipser RD, Little T, Wilson W, et al: Dual effects of antidiuretic hormone on urinary prostaglandin E2 excretion in man. J Clin Endocrinol Metab 53: 522–526, 1981.PubMedCrossRefGoogle Scholar
  39. 39.
    Roche J, Chambez EM, Hostein J, et al: Role des prostaglandines PGE2 dans l’insuffisance rénale fonctionnelle de la cirrhose. Nouv Presse Med 9: 2259–2260, 1980.PubMedGoogle Scholar
  40. 40.
    Lohmeier T, Davis JO, Hanson R, et al: Renin-aldosterone system in rabbits with thoracic caval constriction. Am J Physiol 232: F559–565, 1977.PubMedGoogle Scholar
  41. 41.
    Zipser RD, Myers SI, Needleman P: Stimulation of renal prostaglandin synthesis by the pressor activity of vasopressin. Endocrinology 108: 495–499, 1981.PubMedCrossRefGoogle Scholar
  42. 42.
    Zambraski EJ, Dunn Mk Prostaglandins and renal function in chronic bile duct ligated-cirrhotic dogs. Kidney Ira 19: 218, 1981.Google Scholar
  43. 43.
    Hassid A, Dunn M: Microsomial prostaglandin biosynthesis of human kidney. J Biol Chem 255: 2472, 1980.PubMedGoogle Scholar
  44. 44.
    Morrison AR, Nishikawa K, Needleman P: Thromboxane A2 biosynthesis in the ureter obstructed isolated perfused kidney of the rabbit. J Pharmacol Exp Ther 205: 1–8, 1978.PubMedGoogle Scholar
  45. 45.
    Kawasaki A, Needleman P: A selective thromboxane synthetase inhibitor that is effective in intact tissue. Fed Proc 40: 662, 1981.Google Scholar
  46. 46.
    Zipser RD, Myers SI, Needleman P: Exaggerated prostaglandin and thromboxane synthesis in the renal vein constricted rabbit kidney: Modulators of renal resistance. Circ Res 47: 231–237, 1980.PubMedGoogle Scholar
  47. 47.
    Myers S, Zipser R, Needleman P: Peptide-induced prostaglandin biosynthesis in the renal vein constricted kidney. Biochem J 198: 357–363, 1981.PubMedGoogle Scholar
  48. 48.
    Zipser RD, Radvan G, Duke E, Little TE: Increased urinary thromboxane B2 and reduced prostaglandin E2 in hepatorenal syndrome. Clin Res 30: 468A, 1982.Google Scholar

Copyright information

© Plenum Publishing Corporation 1983

Authors and Affiliations

  • Robert D. Zipser
    • 1
  • Timothy Little
    • 1
  • Hector Ziperovich
    • 1
  • Robert Duke
    • 1
  1. 1.Section of EndocrinologyUniversity of Southern California School of MedicineLos AngelesUSA

Personalised recommendations