Hepatorenal syndrome

Hepatorenal syndrome(HRS) is defined as a functional renal failure in patients with liver disease with portal hypertension and it constitutes the climax of systemic circulatory changes associated with portal hypertension.This term refers to a precisely specified syndrome featuring in particular morphologically intact kidneys,where regulatory mechanisms have minimised glomerular filtration and maximised tubular resorption and urine concentration,which ultimately results in uraemia.The syndrome occurs almost exclusively in patients with ascites.Type 1 HRS develops as a consequence of a severe reduction of effective circulating volume due to both an extreme splanchnic arterial vasodilatation and a reduction of cardiac output.Type 2 HRS is characterised by a stable or slowly progressive renal failure so that its main clinical consequence is not acute renal failure,but refractory ascites,and its impact on prognosis is less negative.Liver transplantation is the most appropriate therapeutic method,nevertheless,only a few patients can receive it.The most suitable "bridge treatments" or treatment for patients ineligible for a liver transplant include terlipressin plus albumin.Terlipressin is at an initial dose of 0.5-1 mg every 4 h by intravenous bolus to 3 mg every 4 h in cases when there is no response.Renal function recovery can be achieved in less than 50% of patients and a considerable decrease in renal function may reoccur even in patients who have been responding to therapy over the short term.Transjugular intrahepatic portosystemic shunt plays only a marginal role in the treatment of HRS.

Management of hepatorenal syndrome

Hepatorenal syndrome （HRS） is defned as development of renal dysfunction in patients with chronic liver diseases due to decreased effective arterial blood volume. It is the most severe complication of cirrhosis because of its very poor prognosis. In spite of several hypotheses and research, the pathogenesis of HRS is still poorly understood. The onset of HRS is a progressive process rather than a suddenly arising phenomenon. Since there are no specifc tests for HRS diagnosis, it is diagnosed by the exclusion of other causes of acute kidney injury in cirrhotic patients. There are two types of HRS with different characteristics and prognostics. Type 1 HRS is characterized by a sudden onset acute renal failure and a rapid deterioration ofother organ functions. It may develop spontaneously or be due to some precipitating factors. Type 2 HRS is characterized by slow and progressive worsening of renal functions due to cirrhosis and portal hypertension and it is accompanied by refractory ascites. The only definitive treatment for both Type 1 and Type 2 HRS is liver transplantation. The most suitable bridge treatment or treatment for patients who are not eligible for transplantation is a combination of terlipressin and albumin. For the same purpose, it is possible to try hemodialysis or renal replacement therapies in the form of continuous veno-venous hemofiltration. Artificial hepatic support systems are important for patients who do not respond to medical treatment.Transjugular intrahepatic portosystemic shunt may be considered as a treatment modality for unresponsive patients to medical treatment. The main goal of clinical surveillance in a cirrhotic patient is prevention of HRS before it develops. The aim of this article is to provide an updated review about the physiopathology of HRS and its treatment.

ALTERATION IN CONTRACTILE RESPONSE TO NORADRENALINE, 5-HYDROXYTRYPTAMINE, S ARAFOTOXIN 6c, AND ANGIOTENSINⅡ IN RAT MESENTERIC ARTERY DURING ORGAN CULTURE

Objective To compare the vasoconstrictive eff ects of 9 mediators on fresh and incubated mesenteric arteries of rats. Methods The superior mesenteric artery of rat was removed and t he endothelium was denuded. The vessels were cut into 1 mm long cylindrical segm ents and subjected to organ culture for 24 hours. Fresh or incubated segments we re immersed into tissue baths and the concentration-response curves were obtain ed by cumulative administration of the vasoconstrictors. Results In fresh mesenteric artery, endothelin-1 (ET-1), 5-h ydroxytryptamine (5-HT), noradrenaline (NA), 5-carboxamidotryptamine (5-CT), and angiotensinⅡ (AngⅡ) induced potent and sustained constrictions in a concen tration-dependent manner. The contraction induced by sarafotoxin 6c (S6c) was w eak, while bradykinin (BK), des-Arg-bradykinin (DA-BK), and human urotensinⅡ (hUT-II) showed no detectable contraction. The concentraion-response curves i n order of slopes was ET-1, NA, 5-HT, 5-CT, and AngⅡ. The order of the maxim um contractions was ET-1>NA=5-HT=5-CT>AngⅡ>S6c. After organ culture, the con centration-response curves induced by S6c, NA, and 5-HT were significantly inc reased, while that induced by AngⅡ was decreased as comparing to fresh arteries . BK contracted the artery only weakly. Conclusion Organ culture changed the phenotypes towards an increased efficacy of NA, 5-HT, S6c, and a reduced efficacy of AngⅡ, which is in accordance with the results o f pharmacological characterization in some human vascular disease.

Current position of vasoconstrictor and albumin infusion for type 1 hepatorenal syndrome

Spontaneous bacterial peritonitis(SBP),refractory ascites,hepatorenal syndrome(HRS),hyponatremia and hepatic encephalopathy are complicationswhich frequently happen during a clinical course of decompensated cirrhosis.Splanchnic and peripheral vasodilatation,increased intrarenal vasoconstriction and impaired cardiac responsive function are pathological changes causing systemic and hemodynamic derangement.Extreme renal vasoconstriction leads to severe reduction of renal blood flow and glomerular filtration rate,which finally evolves into the clinical feature of HRS.Clinical manifestations of type 1 and type 2 HRS come to medical attention differently.Patients with type1 HRS present as acute kidney injury whereas those with type 2 HRS will have refractory ascites as the leading problem.Prompt diagnosis of type 1 HRS can halt the progression of HRS to acute tubular necrosis if the combined treatment of albumin infusion and vasoconstrictors is started timely.HRS reversal was seen in 34%-60%of patients,followed with decreasing mortality.Baseline serum levels of creatinine less than5 mg/dL,bilirubin less than 10 mg/dL,and increased mean arterial pressure of over 5 mmHg by day 3 of the combined treatment of vasoconstrictor and albumin are the predictors of good response.Type 1 HRS can be prevented in some conditions such as albumin infusion in SBP,prophylactic antibiotics for upper gastrointestinal hemorrhage,albumin replacement after large volume paracentesis in cirrhotic patients with massive ascites.The benefit of albumin infusion in infection with primary source other than SBP requires more studies.