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Download PDF Hepatorenal Syndrome: Causes, Tests and Treatment Options

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Terlipressin has been studied the most for individuals with hepatorenal syndrome and early results have shown improved renal function in affected individuals who have taken the terlipressin along with albumin. Albumin is a protein made by the liver. However, more research is necessary to determine the long-term safety and effectiveness of vasoconstrictive agents such as terlipressin for the treatment of individuals with hepatorenal syndrome.

Terlipressin is currently approved for use in Europe for patients with hepatorenal syndrome and trials to get it approved in the US are underway. A non-surgical procedure known as transhepatic portosystemic shunts or TIPS has been used to treat several individuals with hepatorenal syndrome. During this procedure, a small metal device called a stent is placed into the liver to improve blood flow.

The procedure has been successful in reversing kidney dysfunction in individuals with hepatorenal syndrome. TIPS can lower elevated blood pressure within the portal veins portal hypertension — a finding that researchers believe plays a key role in the development of the kidney dysfunction in individuals with liver disease.

More research including proper clinical study is necessary to determine the long-term safety and effectiveness of TIPS for the treatment of individuals with hepatorenal syndrome. Hemodialysis and continuous renal replacement therapy have also been reported as potential treatment options for individuals with hepatorenal syndrome.

However, these therapies are only supportive and not curative. More research is necessary to determine the safety, effectiveness and feasibility of these potential therapies for individuals with hepatorenal syndrome. Information on current clinical trials is posted on the Internet at www. All studies receiving U. For information about clinical trials sponsored by private sources, contact: For information about clinical trials conducted in Europe, contact: Hepatorenal Syndrome Resources Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.

Hepatorenal Syndrome and Liver Transplantation. In Ascites, Hyponatremia and Hepatorenal Syndrome: Frontiers of Gastrointestinal Research. Pretransplant Type 2 hepatorenal syndrome is associated with persistently impaired renal function after liver transplantation. Outcomes of patients with cirrhosis and hepatorenal syndrome Type I treated with liver transplantation.

Hepatorenal syndrome

Liver Transplantation ; Kidney disease in the setting of liver failure: Am J Kidney Dis. Angeli P, Gines P. Hepatorenal syndrome, MELD score and liver transplantation: Journal of Hepatology ; Nephrol Dial Transp ; The challenges of providing renal replacement therapy in decompensated cirrhosis. Recent advances in our understanding of hepatorenal syndrome. Hepatorenal syndrome in the Intensive Care Unit. J Inten Care Med. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome.

Circulatory function and hepatorenal syndrome in cirrhosis. Accessed May 12, Critical care , The content of the website and databases of the National Organization for Rare Disorders NORD is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. These studies show that: The initial dose of terlipressin in many studies ranged from 0. This regimen was maintained until reversal of HRS, which usually occurred within the second week of treatment.

Some refer to central venous pressure to establish and titrate albumin doses and to prevent fluid overload. To date, there have been two pilot studies. Angeli et al 50 used 7. Albumin was also administered to patients in these studies. The results are similar to those observed with terlipressin, although the response was slower. A pilot study has also explored the effect of norepinephrine infusion 0.

Reversal of HRS was achieved in 10 out of 12 cases and was associated with improvement in urinary sodium excretion and decrease in PRA. Norepinephrine is cheaper and more widely available than terlipressin, but it is thought to have a greater propensity to induce cardiac arrhythmias. Most were prospective but uncontrolled studies. The system is also connected to a haemodialysis or haemoperfusion apparatus.

MDS (Myelodysplastic Syndromes)

A few studies reported that systemic haemodynamics improved during ECAD, indicated by an increase in arterial pressure and systemic vascular resistances, and a decrease in cardiac output, PRA and norepinephrine levels. Liver transplantation was the only effective therapy for patients with HRS before the introduction of vasoconstrictors and TIPS, and is still the treatment of choice for these patients.

Definition

In fact, the haemodynamic and neurohormonal abnormalities associated with HRS disappear within the first month after transplantation, and the patients regain their ability to excrete sodium and free water. Improved knowledge of the mechanisms underlying HRS and the development of new treatment strategies are the reasons for the new consensus on definition, diagnostic criteria and HRS treatment modalities organised by the International Ascites Club. HRS is a potentially reversible syndrome that occurs in patients with cirrhosis, ascites and liver failure, as well as in patients with acute liver failure or alcoholic hepatitis.

It is characterised by impaired renal function, marked alterations in cardiovascular function and overactivity of the sympathetic nervous and renin—angiotensin systems. Severe renal vasoconstriction leads to a decrease of GFR. There are two types of HRS. It appears spontaneously, but can also follow a precipitating event.

Adapted from Alessandria et al It may appear spontaneously, but often develops after a precipitating event, particularly SBP. The main differences from the definition reported in 5 are:. As there are no specific hallmarks of HRS, the diagnosis is based on the exclusion of other types of renal failure. The criteria necessary to diagnose HRS are reported in the box below. The main differences between these criteria and those previously established 5 are:. Furthermore, most studies have included too few patients.

Therefore, concepts and practical recommendations given in this part of the article are based on both published data and the personal experience of the panelists, and may be improved upon by further experience gained in the future. The incidence of HRS in patients with SBP may be reduced by albumin administration, prevention which was associated with improved survival. The suggested dose of albumin is 1. Future studies are necessary to define better optimal doses of albumin and the subgroup of patients for whom treatment is highly indicated.

Terlipressin is the most widely studied compound. It should be started at 0. Terlipressin may induce ischaemic side effects and arrhythmias requiring drug discontinuation. Other vasoconstrictors tested in HRS are midodrine, in combination with octreotide, or norepinephrine. The schedules for midodrine and octreotide and those of norepinephrine are reported above. In addition to creatinine levels being useful in adjusting the doses of these vasoconstrictors, blood pressure, renal water and sodium excretion, and serum sodium levels may also be helpful.

The administration of albumin may improve the effect of vasoconstrictors. Since this complication is uncommon, catheterisation to monitor central venous pressure is not mandatory, but careful physical and radiological monitoring of the cardiopulmonary function is recommended. As reported in the text box, three types of response to treatment with vasoconstrictors and albumin can be observed.

Renal failure may recur after discontinuation of therapy relapse , but retreatment is usually effective. In contrast, partial response is frequently followed by a severe and irreversible relapse of renal failure. The major disadvantage of TIPS is its low applicability. The first line of therapy is the use of vasoconstrictors combined with albumin. Patients with partial or no response to vasoconstrictors may be treated with TIPS. The sequential use of vasoconstrictors plus albumin and TIPS in suitable patients is an interesting idea deserving further investigation.

Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis

There are no definite data to support the use of vasoconstrictors in these patients. Data on the effect of TIPS on survival are still insufficient. Experts who participated to the four panels for the preparation of the consensus were the following:. P Gines Spain , panelists: A Gerbes Germany , panelists: F Wong Canada , panelists: National Center for Biotechnology Information , U.

Journal List Gut v. Published online Mar This article has been cited by other articles in PMC. Background The definition and diagnostic criteria for HRS established in 5 were based on the following three concepts: Circulatory dysfunction is characterised by vasodilatation in the splanchnic circulation with a relatively low and insufficient cardiac output, leading to effective hypovolaemia. HRS may occur spontaneously with worsening liver function, or secondary to a precipitating event such as bacterial infection eg, SBP.

Background for the new concepts The first of these concepts was formulated following investigation conducted using Doppler ultrasonography or plethysmography both before and after Open in a separate window. Treatment of HRS New treatments of HRS are designed to expand the central blood volume by simultaneously increasing the total plasma volume and reducing intense peripheral vasodilatation. New treatments of HRS Vasoconstrictors and albumin The use of an analogue of vasopressin to improve renal blood flow in cirrhotic patients was first proposed by Kew et al 35 years ago.

The rate of the creatinine decrease was slower than is usually obtained using terlipressin plus albumin;. Such patients may benefit from simultaneous liver and kidney transplantation. Prophylactic treatment may be beneficial in reducing the risk of developing HRS. Pentoxifylline is a phosphodiesterase inhibitor with beneficial effects on renal function. Patients were randomised into two treatment arms, pentoxifylline or placebo. Baseline, one-month, three-month and sixth-month laboratory and clinical parameters were assessed.

HRS developed in two patients in the pentoxifylline group 2. The six-month mortality was one in two HRS patients in the pentoxifylline group compared with three in ten HRS patients in the placebo group. Over the last century, much has been learnt about the pathophysiology, clinical behaviour, and natural history of HRS. Standardised diagnostic criteria have been developed and implemented worldwide, allowing for more uniform diagnosis and consistent reporting of the disease.

Limitations in the diagnostic criteria exist, but as yet, no reliable diagnostic marker exists for HRS. Future directions should include the development of an accurate diagnostic test for HRS. This is important as an earlier diagnosis and thus treatment is likely to improve survival. Several treatment options exist, but, at present, only liver transplantation offers a genuine hope for cure and longevity. This is a literature review.


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It did not involve any investigations on patients and therefore informed consent was not required. No patient information was included. The authors declare that there is no conflict of interests regarding the publication of this paper. National Center for Biotechnology Information , U. Journal List Gastroenterol Res Pract v. Published online Jan Alexander , 4 and D. Lomas 1 , 3. Received Oct 19; Accepted Dec 9.

Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC. Introduction Hepatorenal syndrome HRS is a unique form of functional renal failure due to diminished renal blood flow, which occurs typically in kidneys that are histologically normal.

Pathophysiology The peripheral arterial vasodilation theory is the most widely accepted explanation for the pathophysiology of HRS Figure 1 [ 1 ], which proposes that splanchnic vasodilation that occurs as a consequence of portal hypertension with cirrhosis is the inciting factor for the development of HRS. Open in a separate window. Historical Developments The concept of HRS has its origins in important incremental discoveries that extend as far back as the 19th century. Diagnostic Criteria and Their Limitations Due to the lack of specific biochemical or radiologic markers, the diagnosis of HRS is based on criteria for excluding other causes of renal impairment that may be found in cirrhosis.

Prognosis HRS is one of the most lethal complications of cirrhosis Figure 2. Treatment Options Vasoconstrictor Therapy. Prophylaxis Prophylactic treatment may be beneficial in reducing the risk of developing HRS. Conclusion Over the last century, much has been learnt about the pathophysiology, clinical behaviour, and natural history of HRS.

Ethical Approval This is a literature review. Conflict of Interests The authors declare that there is no conflict of interests regarding the publication of this paper. Acute kidney injury in cirrhosis. Historical notes on ascites in cirrhosis. Ascites and Renal Dysfunction in Liver Disease: Pathogenesis, Diagnosis and Treatment. Clinical report of hydro-peritoneum, based on analysis of forty-six cases. The American Journal of the Medical Sciences. A liver and kidney syndrome: The Journal of Surgery, Gynecology and Obstetrics. Electrolyte and circulatory changes in terminal liver failure.

Hepatorenal syndrome in cirrhosis: Renal failure in the patient with cirrhosis. The role of active vasoconstriction. The American Journal of Medicine. Functional renal insufficiency in cirrhotics. Archives Francaises des Maladies de l"Appareil Digestif. Transplantation of cadaveric kidneys from patients with hepatorenal syndrome. Evidence for the functionalnature of renal failure in advanced liver disease.

The New England Journal of Medicine. Plasma renin level in hepatic cirrhosis.

Background

Relation to functional renal failure. Sympathetic nervous activity, renin-angiotensin system and renal excretion of prostaglandin E 2 in cirrhosis. Relationship to functional renal failure and sodium and water excretion. European Journal of Clinical Investigation. Sympathetic nervous activity and renal and systemic hemodynamics in cirrhosis: Peripheral arterial vasodilation hypothesis: Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis.

The evaluation of renal function and disease in patients with cirrhosis. Assessing renal function in cirrhotic patients: American Journal of Kidney Diseases. Unpredictability of clinical evaluation of renal function in cirrhosis. Limitations of serum creatinine level and creatinine clearance as filtration markers in cirrhosis.

Archives of Internal Medicine. Working Party proposal for a revised classification system of renal dysfunction in patients with cirrhosis. Medical Clinics of North America. Diagnosis, treatment and survival of patients with hepatorenal syndrome: Retrospective analysis of patients labelled as hepatorenal syndrome in a referral center. American Journal of Gastroenterology. Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Incidence and prognosis of different types of functional renal failure in cirrhotic patients with ascites.

Clinical Gastroenterology and Hepatology. Prognostic importance of the cause of renal failure in patients with cirrhosis. Model for end-stage liver disease score and systemic inflammatory response are major prognostic factors in patients with cirrhosis and acute functional renal failure.

Renal dysfunction in cirrhosis. Oxford Textbook of Clinical Hepatology. Oxford University Press; Renal failure in acute liver failure. European Journal of Gastroenterology and Hepatology. Prevalence of septic events, type 1 hepatorenal syndrome, and mortality in severe alcoholic hepatitis and utility of discriminant function and MELD score in predicting these adverse events.

Digestive Diseases and Sciences. Clinical Journal of the American Society of Nephrology. Renal impairment after spontaneous bacterial peritonitis in cirrhosis: Tumor necrosis factor and interleukin-6 in spontaneous bacterial peritonitis in cirrhosis: Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Renal failure after upper gastrointestinal bleeding in cirrhosis: Incidence, clinical course, predictive factors, and short-term prognosis. Bile acids, oxidative stress, and renal function in biliary obstruction.