Hepatorenal syndrome medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sunny Kumar MD [2]

Overview

HRS may develop in two clinical types as an acute and rapidly progressive renal failure (AKI-HRS) or as chronic and not progressive renal failure (CKD-HRS) which can be managed with medications but the end treatment depends on liver transplant.

Medical Therapy

Because of the high mortality associated with hepatorenal syndrome, emphasis is on prevention in patients who are at risk for the condition. Strategies for avoiding hepatorenal syndrome include appropriate and non-aggressive use of diuretics, identification and early treatment of infection and hemorrhage, and avoidance of other toxins that can affect both the liver and kidney.[1]

The definitive treatment for hepatorenal syndrome is liver transplantation, and all other therapies can best be described as bridges to transplantation. These treatment strategies include the following:[2]

Albumin

All major studies showing improvement in renal function in patients with hepatorenal syndrome have involved expansion of the volume of the plasma with albumin given intravenously [3][4] One regimen is 1 gm albumin per kg of body weight intravenously on day one followed by followed by 20-40 grams daily.[5]

Midodrine and octreotide

Midodrine is an alpha-agonist and octreotide is an analogue of somatostatin. The medications are respectively systemic vasoconstrictors and inhibitors of vasodilators, and were not found to be useful when used individually in treatment of hepatorenal syndrome.[6] However, one study of 13 patients with hepatorenal syndrome showed significant improvement when the two were used together (with midodrine given orally, octreotide given subcutaneously and both dosed according to blood pressure), with three patients surviving to discharge.[7] A nonrandomized, observational study used "100 μg subcutaneously TID, with the goal to increase the dose to 200 μg subcutaneous TID" and "midodrine administration started at 5, 7.5, or 10 mg TID orally, with the goal to increase the dose to 12.5 or 15 mg if necessary" and found that "octreotide/midodrine treatment appears to improve 30-day survival".[8]

Vasopressin analogues

The vasopressin analogue ornipressin was found in a number of studies to be useful in improvement of renal function in patients with hepatorenal syndrome,[3][9] but has been limited by ischemic complications[3]. Terlipressin is a vasopressin analogue that has been found in one study to be useful for improving renal function in patients with hepatorenal syndrome with a lesser incidence of ischemia.[4] Neither medication is available for use in North America.

Transjugular intrahepatic portosystemic shunt

TIPS, shown in progress here, has been shown to improve renal function in individuals with HRS if portal pressures decrease after the procedure.

Transjugular intrahepatic portosystemic shunts (TIPS) involve decompression of the high pressures in the portal circulation by placing a small stent between a portal and hepatic vein. They have also been shown to improve renal function in patients with hepatorenal syndrome.[10][11]

Liver dialysis

Liver dialysis involves extracorporeal dialysis to remove toxins from the circulation. The molecular adsorbents recirculation system (MARS) has shown some utility as a bridge to transplantation in patients with hepatorenal syndrome.[12]

Hemodialysis

Renal replacement therapy may be required to 'bridge' the patient to liver transplantation, although the condition of the patient may dictate the modality used.[13]

Other medications

Other agents used in treatment include

Recommendations for the treatment of Hepatorenal Syndrome (DO NOT EDIT)

  1. Albumin infusion plus administration of vasoactive drugs such as octreotide and midodrine should be considered in the treatment of type I hepatorenal syndrome.
  2. Patients with cirrhosis, ascites, and type I hepatorenal syndrome should have an expedited referral for liver transplantation.

References

  1. Cavallin M, Fasolato S, Marenco S, Piano S, Tonon M, Angeli P (2015). "The Treatment of Hepatorenal Syndrome". Dig Dis. 33 (4): 548–54. doi:10.1159/000375346. PMID 26159272.
  2. Fabrizi F, Aghemo A, Messa P (2013). "Hepatorenal syndrome and novel advances in its management". Kidney Blood Press Res. 37 (6): 588–601. doi:10.1159/000355739. PMID 24356549.
  3. 3.0 3.1 3.2 Guevara M, Gines P, Fernandez-Esparrach G, Sort P, Salmeron JM, Jimenez W, Arroyo V, Rodes J. Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion. Hepatology 1998 Jan;27(1):35-41. PMID 9425914
  4. 4.0 4.1 Ortega R, Gines P, Uriz J, Cardenas A, Calahorra B, De Las Heras D, Guevara M, Bataller R, Jimenez W, Arroyo V, Rodes J. Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study. Hepatology 2002 Oct;36 (4 Pt 1):941-8. PMID 12297842
  5. Ginès P, Cárdenas A, Arroyo V, Rodés J (2004). "Management of cirrhosis and ascites". N. Engl. J. Med. 350 (16): 1646–54. doi:10.1056/NEJMra035021. PMID 15084697.
  6. Pomier-Layrargues G, Paquin SC, Hassoun Z, Lafortune M, Tran A. Octreotide in hepatorenal syndrome: a randomized, double-blind, placebo-controlled, crossover study. Hepatology 2003 Jul;38(1):238-43.
  7. Angeli P, Volpin R, Gerunda G, Craighero R, Roner P, Merenda R, Amodio P, Sticca A, Caregaro L, Maffei-Faccioli A, Gatta A. Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide. Hepatology 1999 Jun;29(6):1690-7. PMID 10347109
  8. Esrailian E, Pantangco ER, Kyulo NL, Hu KQ, Runyon BA (2007). "Octreotide/Midodrine therapy significantly improves renal function and 30-day survival in patients with type 1 hepatorenal syndrome". Dig. Dis. Sci. 52 (3): 742–8. doi:10.1007/s10620-006-9312-0. PMID 17235705.
  9. Gulberg V, Bilzer M, Gerbes AL. Long-term therapy and retreatment of hepatorenal syndrome type 1 with ornipressin and dopamine. Hepatology 1999 Oct;30(4):870-5. PMID 10498636
  10. Wong F, Pantea L, Sniderman K. Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology. 2004 Jul;40(1):55-64. PMID 15239086.
  11. Guevara M, Rodes J. Hepatorenal syndrome. Int J Biochem Cell Biol. 2005 Jan;37(1):22-6. PMID 15381144.
  12. Mitzner SR, Stange J, Klammt S, Risler T, Erley CM, Bader BD, Berger ED, Lauchart W, Peszynski P, Freytag J, Hickstein H, Loock J, Lohr JM, Liebe S, Emmrich J, Korten G, Schmidt R. Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial. Liver Transpl. 2000 May;6(3):277-86. PMID 10827226.
  13. Witzke O, Baumann M, Patschan D, Patschan S, Mitchell A, Treichel U, Gerken G, Philipp T, Kribben A. Which patients benefit from hemodialysis therapy in hepatorenal syndrome? J Gastroenterol Hepatol. 2004 Dec;19(12):1369-73. PMID 15610310
  14. Holt S, Goodier D, Marley R, Patch D, Burroughs A, Fernando B, Harry D, Moore K. Improvement in renal function in hepatorenal syndrome with N-acetylcysteine. Lancet. 1999 Jan 23;353(9149):294-5. PMID 9929029
  15. Clewell JD, Walker-Renard P. Prostaglandins for the treatment of hepatorenal syndrome. Ann Pharmacother. 1994 Jan;28(1):54-5. PMID 8123962

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