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Medication

Medication Summary

The pharmacological approach to the treatment of hepatorenal syndrome (HRS) continues to evolve, with several possible effective treatments.

Terlipressin gained FDA approval in September 2022 to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function.

However, readers should be aware that most of these medications have yet to be validated in randomized controlled trials. A brief review of only the most promising (but yet unproven) medications will be described, because not only is this historical list extensive, but most of the trials for the medications were conducted outside the United States.

Class Summary

Vasopressin analogues improve circulatory dysfunction secondary to splanchnic vasodilatation. These agents also improve renal plasma flow (RPF), the glomerular filtration rate (GFR), and urine output.

Terlipressin

Terlipressin is a synthetic vasopressin analogue with twice the selectivity for vasopressin V1 receptors versus V2 receptors. This agent acts as both a prodrug of lysine-vasopressin, and it also has pharmacologic activity on its own. It is indicated to improve kidney function in adults with HRS with rapid reduction in kidney function.

Class Summary

Antibiotics are only indicated in the treatment of hepatorenal syndrome (HRS) if renal dysfunction is precipitated by an infection. Prophylactic antibiotics may play a role in preventing spontaneous bacterial peritonitis (SBP), which, in turn, is also a risk factor for the development of HRS-acute kidney injury (AKI) (formerly type 1 HRS) in patients with type 2 HRS. The efficacy and safety of prophylactic antibiotics remains to be established because of reports of emergent resistant bacteria. May play an important role in selected patients, such as those awaiting liver transplantation, although the duration (long-term vs cyclic) remains to be determined.

Cefotaxime (Claforan)

Because the most common cause of HRS-AKI is SBP, IV cefotaxime is the drug of choice (DOC).

Ciprofloxacin (Cipro)

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Ciprofloxacin is a fluoroquinolone with activity against pseudomonads, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms, but it has no activity against anaerobes. It inhibits bacterial DNA synthesis and, consequently, growth.

Norfloxacin (Noroxin, Chibroxin)

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Norfloxacin is a fluoroquinolone with activity against pseudomonads, streptococci, MRSA, S epidermidis, and most gram-negative organisms, but it has no activity against anaerobes. It inhibits bacterial DNA synthesis and, consequently, growth.

Sulfamethoxazole and trimethoprim (Bactrim, Bactrim DS, Septra, Septra DS)

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Sulfamethoxazole and trimethoprim inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid.

Class Summary

Somatostatin analogues aid improvement in splanchnic circulation, which may improve renal hemodynamics.

Octreotide (Sandostatin)

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Octreotide is a synthetic derivative of somatostatin. It is a potent physiologic inhibitor of several gastrointestinal functions, one of which is a reduction in intestinal blood flow by splanchnic vasoconstriction.

Class Summary

Experimental evidence demonstrates antioxidants aid improvement of renal function in acute cholestasis and renal failure.

N-acetylcysteine (Mucomyst)

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N-acetylcysteine is traditionally used to treat acetaminophen overdose. It replenishes low hepatic glutathione stores to prevent the synthesis of toxic epoxide intermediates. This agent does not have a role in the treatment of non–acetaminophen-related liver failure. Its exact mechanism of action in HRS remains unclear.

Class Summary

Plasma volume expanders are indicated for the correction of abnormal hemodynamic parameters.

Albumin (Albunex, Albuminar, Albumisol)

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Albumin is useful for plasma volume expansion and maintenance of cardiac output.

Class Summary

Sympathomimetic agents improve renal artery perfusion.

Dopamine (Intropin)

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Dopamine stimulates both adrenergic and dopaminergic receptors. Its hemodynamic effect is dependent on dose. Lower doses predominantly stimulate dopaminergic receptors, which, in turn, produce renal and mesenteric vasodilation. Cardiac stimulation and renal vasodilation are produced by higher doses. This agent is described for its historical interest, because it has no role in monotherapy for HRS. However, reversal of HRS has been described when dopamine was used at low doses in conjunction with ornipressin.

Questions

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Author

Deepika Devuni, MD Assistant Professor of Gastroenterology, University of Massachusetts Medical School

Deepika Devuni, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Association of Physicians of Indian Origin, American College of Gastroenterology, American Gastroenterological Association, American Society of Transplantation

Disclosure: SIte PI for: Sequana Medical .

Coauthor(s)

Emily Weng, DO Fellow, Division of Gastroenterology and Hepatology, Department of Medicine, University of Connecticut School of Medicine

Emily Weng, DO is a member of the following medical societies: American Academy of Osteopathy, American College of Gastroenterology, American College of Physicians, Student Osteopathic Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Acknowledgements

Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Hemant K Roy, MD Associate Professor of Medicine, Section of Gastroenterology, Feinberg School of Medicine at Northwestern University, Evanston-Northwestern Healthcare

Disclosure: Nothing to disclose.

Rowen K Zetterman, MD Director, Faculty Mentoring Programs, University of Nebraska Medical Center; Dean Emeritus, Creighton University School of Medicine

Rowen K Zetterman, MD, is a member of the following medical societies: Alpha Omega Alpha, American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, and American Medical Association

Disclosure: Nothing to disclose.

Hepatorenal Syndrome Medication

Medication Summary

Vasopressin analogues

Class Summary

Terlipressin

Antibiotics

Class Summary