The hepatorenal syndrome(HRS)is one major extrahepatic complication of endstage liver diseases.While circulatory dysregulation is considered as primary etiology for HRS,cirrhosis-related(systemic)inflammation and/or c...The hepatorenal syndrome(HRS)is one major extrahepatic complication of endstage liver diseases.While circulatory dysregulation is considered as primary etiology for HRS,cirrhosis-related(systemic)inflammation and/or cardial dysfunction may also play a key pathogenic role in HRS development.Exclusion of other causes of acute kidney injury(AKI)is required for diagnosis of HRS-AKI by the definition of the International Club of Ascites.However,the pathophysiology of HRS is not understood completely and there are still limited therapeutic options.Reversibility of renal dysfunction after liver transplantation indicates that HRS-AKI is a functional disorder caused by altered cellular function.The interplay between systemic inflammation and the onset of kidneyrelated hypometabolism may have a key role and needs to be studied in depth.This minireview challenges simplified views of the HRS in the context of diagnostics and therapy stressing the need for further evidence to advance the knowledge on this syndrome.展开更多
Hepatorenal syndrome with acute kidney injury(HRS-AKI)is a form of rapidly progressive kidney dysfunction in patients with decompensated cirrhosis and/or acute severe liver injury such as acute liver failure.Current d...Hepatorenal syndrome with acute kidney injury(HRS-AKI)is a form of rapidly progressive kidney dysfunction in patients with decompensated cirrhosis and/or acute severe liver injury such as acute liver failure.Current data suggest that HRS-AKI occurs secondary to circulatory dysfunction characterized by marked splanchnic vasodilation,leading to reduction of effective arterial blood volume and glomerular filtration rate.Thus,volume expansion and splanchnic vasoconstriction constitute the mainstay of medical therapy.However,a significant proportion of patients do not respond to medical management.These patients often require renal replacement therapy and may be eligible for liver or combined liver-kidney transplantation.Although there have been advances in the management of patients with HRS-AKI including novel biomarkers and medications,better-calibrated studies,more widely available biomarkers,and improved prognostic models are sorely needed to further improve diagnosis and treatment of HRS-AKI.展开更多
[Objectives]This study was conducted to evaluate the protective effect of polysaccharides from Enteromorpha prolifera(PEP)on mice with hepatorenal syndrome induced by carbon tetrachloride.[Methods]A mouse hepatorenal ...[Objectives]This study was conducted to evaluate the protective effect of polysaccharides from Enteromorpha prolifera(PEP)on mice with hepatorenal syndrome induced by carbon tetrachloride.[Methods]A mouse hepatorenal syndrome model was induced by carbon tetrachloride.The serum levels of lipid,total antioxidant capacity,liver and kidney function,pathological changes of liver and kidney were selected to clarity the effectiveness of PEP on hepatorenal syndrome in mice.[Results]PEP effectively lowered the serum levels of lipid,increased total antioxidant capacity,improved liver and kidney injury,and alleviated pathological changes of liver and kidney of mice induced by carbon tetrachloride.[Conclusions]PEP has a potent preventive effect on hepatorenal syndrome induced by carbon tetrachloride in mice,which provides theoretical support for future clinical application of PEP.展开更多
Hepatorenal syndrome(HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation(LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40...Hepatorenal syndrome(HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation(LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40%, respectively. In this article, we reviewed current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver alone vs simultaneous liver kidney transplant(SLKT) in transplant candidates. Many treatment options including albumin, vasoconstrictors, renal replacement therapy, and eventual LT have remained a mainstay in the treatment of HRS. Unfortunately, even after aggressive measures such as terlipressin use, the rate of recovery is less than 50% of patients. Moreover, current SLKT guidelines include:(1) estimation of glomerular filtration rate of 30 m L/min or less for 4-8 wk;(2) proteinuria > 2 g/d; or(3) biopsy proven interstitial fibrosis or glomerulosclerosis. Even with these updated criteria there is a lack of consistency regarding longterm benefits for SLKT vs LT alone. Finally, in regards to kidney dysfunction in the post-transplant setting, an estimation of glomerular filtration rate < 60 mL /min per 1.73 m2 may be associated with an increased risk of patients having long-term end stage renal disease. HRS is common in patients with cirrhosis and those on liver transplant waitlist. Prompt identification and therapy initiation in transplant candidates with HRS may improve post-transplantation outcomes. Future studies identifying optimal vasoconstrictor regimens, alternative therapies, and factors predictive of response to therapy are needed. The appropriate use of SLKT in patients with HRS remains controversial and requires further evidence by the transplant community.展开更多
Acute kidney injury(AKI)in cirrhosis,including hepatorenal syndrome(HRS),is a common and serious complication in cirrhotic patients,leading to significant morbidity and mortality.AKI is separated into two categories,n...Acute kidney injury(AKI)in cirrhosis,including hepatorenal syndrome(HRS),is a common and serious complication in cirrhotic patients,leading to significant morbidity and mortality.AKI is separated into two categories,non-HRS AKI and HRS-AKI.The most recent definition and diagnostic criteria of AKI in cirrhosis and HRS have helped diagnose and prognosticate the disease.The pathophysiology behind non-HRS-AKI and HRS is more complicated than once theorized and involves more processes than just splanchnic vasodilation.The common biomarkers clinicians use to assess kidney injury have significant limitations in cirrhosis patients;novel biomarkers being studied have shown promise but require further studies in clinical settings and animal models.The overall management of non-HRS AKI and HRS-AKI requires a systematic approach.Although pharmacological treatments have shown mortality benefit,the ideal HRS treatment option is liver transplantation with or without simultaneous kidney transplantation.Further research is required to optimize pharmacologic and nonpharmacologic approaches to treatment.This article reviews the current guidelines and recommendations of AKI in cirrhosis.展开更多
Hepatorenal syndrome(HRS) is a manifestation of extreme circulatory dysfunction and entails high morbidity and mortality.A new definition has been recently recommended by the International Club of Ascites,according to...Hepatorenal syndrome(HRS) is a manifestation of extreme circulatory dysfunction and entails high morbidity and mortality.A new definition has been recently recommended by the International Club of Ascites,according to which HRS diagnosis relies in serum creatinine changes instead that on a fixed high value.Moreover,new data on urinary biomarkers has been recently published.In this sense,the use of urinary neutrophil gelatinase-associated lipocalin seems useful to identify patients with acute tubular necrosis and should be employed in the diagnostic algorithm.Treatment with terlipressin and albumin is the current standard of care.Recent data show that terlipressin in intravenous continuous infusion is better tolerated than intravenous boluses and has the same efficacy.Terlipressin is effective in reversing HRS in only 40%-50% of patients.Serum bilirubin and creatinine levels along with the increase in blood pressure and the presence of systemic inflammatory response syndrome have been identified as predictors of response.Clearly,there is a need for further research in novel treatments.Other treatments have been assessed such as noradrenaline,dopamine,transjugular intrahepatic portosystemic shunt,renal and liver replacement therapy,etc.Among all of them,liver transplant is the only curative option and should be considered in all patients.HRS can be prevented with volume expansion with albumin during spontaneous bacterial peritonitis and after post large volume paracentesis,and with antibiotic prophylaxis in patients with advanced cirrhosis and low proteins in the ascitic fluid.This manuscript reviews the recent advances in the diagnosis and management of this life-threatening condition.展开更多
Terlipressin has been shown to improve both pulmonary and systemic hemodynamics in stable cirrhotic patients with pulmonary hypertension,whereas other vasoconstrictors may cause pulmonary pressures to deteriorate We i...Terlipressin has been shown to improve both pulmonary and systemic hemodynamics in stable cirrhotic patients with pulmonary hypertension,whereas other vasoconstrictors may cause pulmonary pressures to deteriorate We investigated the pulmonary and systemic hemodynamic effects of the first terlipressin dose(2 mg) in 7 cirrhotic patients with PH presenting with variceal bleeding(n=4) or hepatorenal syndrome(n=3).Terlipressin decreased pulmonary vascular resistance(158.8±8.9 vs 186.5±13.9 dynes sec cm-5 ;P=0.003) together with an increase in systemic vascular resistance(2143± 126 vs 1643±126 dynes sec cm-5 ;P<0.001).Terlipressin should be the vasoconstrictor treatment of choice when patients present with variceal bleeding or HRS.展开更多
Spontaneous bacterial peritonitis(SBP),refractory ascites,hepatorenal syndrome(HRS),hyponatremia and hepatic encephalopathy are complicationswhich frequently happen during a clinical course of decompensated cirrhosis....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.展开更多
BACKGROUND Hepatorenal syndrome(HRS)is a severe complication of cirrhosis with high mortality,which necessitates accurate clinical decision.However,studies on prognostic factors and scoring systems to predict overall ...BACKGROUND Hepatorenal syndrome(HRS)is a severe complication of cirrhosis with high mortality,which necessitates accurate clinical decision.However,studies on prognostic factors and scoring systems to predict overall survival of HRS are not enough.Meanwhile,a multicenter cohort study with a long span of time could be more convincing.AIM To develop a novel and effective prognostic model for patients with HRS and clarify new prognostic factors.METHODS We retrospectively enrolled 1667 patients from four hospitals,and 371 eligible patients were finally analyzed to develop and validate a novel prognostic model for patients with HRS.Characteristics were compared between survivors and non-survivors,and potential prognostic factors were selected according to the impact on 28-d mortality.Accuracy in predicting 28-d mortality was compared between the novel and other scoring systems,including Model for End-Stage Liver Disease(MELD),Chronic Liver Failure-Sequential Organ Failure Assessment(CLIF-SOFA),and Chinese Group on the Study of Severe Hepatitis BAcute-on-Chronic Liver Failure(COSSH-ACLF).RESULTS Five prognostic factors,comprised of gender,international normalized ratio,mean corpuscular hemoglobin concentration,neutrophil percentage,and stage,were integrated into a new score,GIMNS;stage is a binary variable defined by the number of failed organs.GIMNS was positively correlated with MELD,CLIFSOFA,and COSSH-ACLF.Additionally,it had better accuracy[area under the receiver operating characteristic curve(AUROC):0.830]than MELD(AUROC:0.759),CLIF-SOFA(AUROC:0.767),and COSSH-ACLF(AUROC:0.759)in the derivation cohort(P<0.05).It performed better than MELD and CLIF-SOFA in the validation cohort(P<0.050)and had a higher AUROC than COSSH-ACLF(P=0.122).CONCLUSION We have developed a new scoring system,GIMNS,to predict 28-d mortality of HRS patients.Mean corpuscular hemoglobin concentration and stage were first proposed and found to be related to the mortality of HRS.Additionally,the GIMNS score showed better accuracy than MELD and CLIF-SOFA,and the AUROC was higher than that of COSSH-ACLF.展开更多
Objective:To evaluate a novel polyherbal formulation(BSVT)containing the standardized extracts from the leaves of Boerhavia diffusa,Solidago virgaurea,Vitex negundo,and thymoquinone in CCl4 induced hepatorenal toxicit...Objective:To evaluate a novel polyherbal formulation(BSVT)containing the standardized extracts from the leaves of Boerhavia diffusa,Solidago virgaurea,Vitex negundo,and thymoquinone in CCl4 induced hepatorenal toxicity in rats.Methods:A total of 36 rats were divided into six groups including normal control,CCl4(2 mL/kg,i.p.),CCl4(2 mL/kg,i.p.)+Cystone?(750 mg/kg p.o.),CCl4(2 mL/kg,i.p.)+BSVT(25 mg/kg,p.o.),CCl4(2 mL/kg,i.p.)+BSVT(50 mg/kg,p.o.),and CCl4(2 mL/kg,i.p.)+BSVT(100 mg/kg,p.o.).All treatments were given for four weeks.Serum levels of aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,total protein,serum urea,blood urea nitrogen and creatinine were assessed.Superoxide dismutase,malondialdehyde,and glutathione peroxidase were evaluated in tissue homogenate.The histopathological study of liver and kidney tissues was also done.Results:Aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,serum urea,blood urea nitrogen and creatinine were significantly elevated(P<0.001)while total protein was considerably reduced in the CCl4 group as compared to the normal control(P<0.001),which indicated hepatorenal toxicity.In addition,superoxide dismutase and glutathione peroxidase activities were significantly decreased(P<0.001)while malondialdehyde levels were increased markedly(P<0.001).Treatment with BSVT formulation recovered these parameters towards a normal level in a dose-dependent manner.Conclusions:BSVT formulation ameliorates the hepatorenal toxicity in a dose-dependent manner.Furthermore,clinical studies are required to confirm its efficacy.展开更多
AIM: To investigate clinical and biochemical features of hepatorenal syndrome(HRS), to assess short and long- term survival evaluating potential predictors of early mortality. METHODS: Sixty-two patients with liver ci...AIM: To investigate clinical and biochemical features of hepatorenal syndrome(HRS), to assess short and long- term survival evaluating potential predictors of early mortality. METHODS: Sixty-two patients with liver cirrhosis and renal failure, defined as a serum creatinine value > 1.5 mg/dL on at least two measurements within 48 h, admitted to our tertiary referral Unit from 2001 to 201, were retrospectively reviewed. Among them, 33 patients(53.2%) fulfilled the revised criteria of the International Ascites Club for the diagnosis of HRS. Twenty-eight patients were treated with combinations of terlipressin and albumin, two with dopamine and al- bumin, and three with albumin alone. No patients were suitable for liver transplantation. Complete response was defined as normalization of creatinine levels to less than 1.5 mg/dL, partial response as a decrease of at least 50% but not to less than 1.5 mg/dL, no response as no reduction in creatinine or a decrease of less 50% compared to pre-treatment values. All of the patients were followed up for at least 1 year until January 2013. RESULTS: HRS type 1 was diagnosed in 15 patients(45.5%). Hepatitis C virus infection was the primary etiology(69.6%), followed by alcohol(15.2%), and cryptogenesis(15.2%). Complete response to therapy was obtained in only 3 cases(9.1%) and partial re- sponse in 7 patients(21.2%). Median survival was 30 d(range: 10-274) without significant differences be- tween type 1 and type 2 HRS. By univariate analysis, Child-Pugh class C(P = 0.009), presence of hepatocel- lular carcinoma(P = 0.04), low serum sodium(P = 0.02), high bilirubin values(P = 0.009) and high Model for End-stage Liver Disease(MELD) score(P = 0.03) were predictive factors of 30-d mortality. By multivari- ate analysis, only serum sodium < 132 mEq/L(OR = 31.39; P = 0.02) and MELD score > 27(OR = 18.72; P = 0.01) were independently associated with a survival of less than one month. CONCLUSION: HRS still has a poor prognosis, even when vasoactive drug therapies are extensively used.展开更多
AIM:To develop a practical and reproducible rat model of hepatorenal syndrome for further study of the pathophysiology of human hepatorenal syndrome. METHODS:Sprague-Dawley rats were intravenously injected with D-gala...AIM:To develop a practical and reproducible rat model of hepatorenal syndrome for further study of the pathophysiology of human hepatorenal syndrome. METHODS:Sprague-Dawley rats were intravenously injected with D-galactosamine and lipopolysaccharide(LPS) via the tail vein to induce fulminant hepatic failure to develop a model of hepatorenal syndrome. Liver and kidney function tests and plasma cytokine levels were measured after D-galactosamine/LPS administration,and hepatic and renal pathology was studied. Glomerular filtration rate was detected in conscious rats using micro-osmotic pump technology with fluorescein isothiocyanate-labelled inulin as a surrogate marker.RESULTS:Serum levels of biochemical indicators including liver and kidney function indexes and cytokines all significantly changed,especially at 12 h after D-galactosamine/LPS administration [alanine aminotransferase,3389.5 ± 499.5 IU/L; blood urea nitrogen,13.9 ± 1.3 mmol/L; Cr,78.1 ± 2.9 μmol/L; K+,6.1 ± 0.5 mmol/L; Na+,130.9 ± 1.9 mmol/L; Cl-,90.2 ± 1.9 mmol/L; tumor necrosis factor-α,1699.6 ± 599.1 pg/m L; endothelin-1,95.9 ± 25.9 pg/m L; P < 0.05 compared with normal saline control group]. Hepatocyte necrosis was aggravated gradually,which was most significant at 12 h after treatment with D-galactosamine/LPS,and was characterized by massive hepatocyte necrosis,while the structures of glomeruli,proximal and distal tubules were normal. Glomerular filtration rate was significantly decreased to 30%-35% of the control group at 12 h after D-galactosamine/LPS administration [Glomerular filtration rate(GFR)1,0.79 ± 0.11 m L/min; GFR2,3.58 ± 0.49 m L/min·kg BW-1; GFR3,0.39 ± 0.99 m L/min·g KW-1]. The decreasing timing of GFR was consistent with that of the presence of hepatocyte necrosis and liver and kidney dysfunction.CONCLUSION:The joint use of D-galactosamine and LPS can induce liver and kidney dysfunction and decline of glomerular filtration rate in rats which is a successful rat model of hepatorenal syndrome.展开更多
AIM To propose several alternatives treatment of type 1 hepatorenal syndrome(HRS-1) what is the most severe expression of circulatory dysfunction on patients with portal hypertension.METHODS A group of eleven gastroen...AIM To propose several alternatives treatment of type 1 hepatorenal syndrome(HRS-1) what is the most severe expression of circulatory dysfunction on patients with portal hypertension.METHODS A group of eleven gastroenterologists and nephrologists performed a structured analysis of available literature.Each expert was designated to review and answer a question.They generated draft statements for evaluation by all the experts.Additional input was obtained from medical community.In order to reach consensus,a modified three-round Delphi technique method was used.According to United States Preventive Services Task Force criteria,the quality of the evidence and level of recommendation supporting each statement was graded.RESULTS Nine questions were formulated.The available evidence was evaluated considering its quality,number of patients included in the studies and the consistency of its results.The generated questions were answered by the expert panel with a high level of agreement.Thus,a therapeutic algorithm was generated.The role of terlipressin and norepinephrine was confirmed as the pharmacologic treatment of choice.On the other hand the use of the combination of octreotide,midodrine and albumin without vasoconstrictors was discouraged.The role of several other options was also evaluated and the available evidence was explored and discussed.Liver transplantation is considered the definitive treatment for HRS-1.The present consensus is an important effort that intends to organize the available strategies based on the available evidence in the literature,the quality of the evidence and the benefits,adverse effects and availability of the therapeutic tools described.CONCLUSION Based on the available evidence the expert panel was able to discriminate the most appropriate therapeutic alternatives for the treatment of HRS-1.展开更多
AIM To detect the expression of typeⅠ inositol 1,4,5-trisphosphate receptor(IP3 RI) in the kidney of rats with hepatorenal syndrome(HRS).METHODS One hundred and twenty-five Sprague-Dawley rats were randomly divided i...AIM To detect the expression of typeⅠ inositol 1,4,5-trisphosphate receptor(IP3 RI) in the kidney of rats with hepatorenal syndrome(HRS).METHODS One hundred and twenty-five Sprague-Dawley rats were randomly divided into four groups to receive an intravenous injection of D-galactosamine(D-Gal N) plus lipopolysaccharide(LPS; group G/L, n = 50), D-Gal N alone(group G, n = 25), LPS alone(group L, n = 25), and normal saline(group NS, n = 25), respectively.At 3, 6, 9, 12, and 24 h after injection, blood, liver, and kidney samples were collected. Hematoxylineosin staining of liver tissue was performed to assess hepatocyte necrosis. Electron microscopy was used to observe ultrastructural changes in the kidney. Western blot analysis and real-time PCR were performed to detect the expression of IP3 RI protein and m RNA in the kidney, respectively.RESULTS Hepatocyte necrosis was aggravated gradually, which was most significant at 12 h after treatment with D-galactosamine/lipopolysaccharide, and was characterized by massive hepatocyte necrosis. At the same time, serum levels of biochemical indicators including liver and kidney function indexes were all significantly changed. The structure of the renal glomerulus and tubules was normal at all time points. Western blot analysis indicated that IP3 RI protein expression began to rise at 3 h(P < 0.05) and peaked at 12 h(P < 0.01). Real-time PCR demonstrated that IP3 RI m RNA expression began to rise at 3 h(P < 0.05) and peaked at 9 h(P < 0.01).CONCLUSION IP3 RI protein expression is increased in the kidney of HRS rats, and may be regulated at the transcriptional level.展开更多
BACKGROUND Hepatorenal syndrome(HRS)is a life-threatening condition among patients with advanced liver disease.Data trends specific to hospital mortality and hospital admission resource utilization for HRS remain limi...BACKGROUND Hepatorenal syndrome(HRS)is a life-threatening condition among patients with advanced liver disease.Data trends specific to hospital mortality and hospital admission resource utilization for HRS remain limited.AIM To assess the temporal trend in mortality and identify the predictors for mortality among hospital admissions for HRS in the United States.METHODS We used the National Inpatient Sample database to identify an unweighted sample of 4938 hospital admissions for HRS from 2005 to 2014(weighted sample of 23973 admissions).The primary outcomes were temporal trends in mortality as well as predictors for hospital mortality.We estimated odds ratios from multilevel mixed effect logistic regression to identify patient characteristics and treatments associated with hospital mortality.RESULTS Overall hospital mortality was 32%.Hospital mortality decreased from 44%in 2005 to 24%in 2014(P<0.001),while there was an increase in the rate of liver transplantation(P=0.02),renal replacement therapy(P<0.001),length of hospital stay(P<0.001),and hospitalization cost(P<0.001).On multivariable analysis,older age,alcohol use,coagulopathy,neurological disorder,and need for mechanical ventilation predicted higher hospital mortality,whereas liver transplantation,transjugular intrahepatic portosystemic shunt,and abdominal paracentesis were associated with lower hospital mortality.CONCLUSION Although there was an increase in resource utilizations,hospital mortality among patients admitted for HRS significantly improved.Several predictors for hospital mortality were identified.展开更多
There is a need to reassess the application of MELD and the impact of renal insufficiency with consideration for developing an algorithm with exception points that would lead to timely allocation of livers to patients...There is a need to reassess the application of MELD and the impact of renal insufficiency with consideration for developing an algorithm with exception points that would lead to timely allocation of livers to patients with hepatorenal syndrome prior to occurrence of permanent renal damage without jeopardizing post-transplant survival.展开更多
Coronavirus disease 2019(COVID-19)is a highly infectious disease which emerged into a global pandemic.Although it primarily causes respiratory symptoms for affected patients,COVID-19 was shown to have multi-organ mani...Coronavirus disease 2019(COVID-19)is a highly infectious disease which emerged into a global pandemic.Although it primarily causes respiratory symptoms for affected patients,COVID-19 was shown to have multi-organ manifestations.Elevated liver enzymes appear to be commonly observed during the course of COVID-19,and there have been numerous reports of liver injury secondary to COVID-19 infection.It has been established that patients with pre-existing chronic liver disease(CLD)are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD.Co-morbidities such as diabetes,hypertension,obesity,cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD,and a substantial population may also live with some degree of frailty.The mechanisms of how COVID-19 induces liver injury have been postulated.Hepatorenal syndrome(HRS)is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause,and is usually a marker of severe decompensated liver disease.Select reports of HRS following acute COVID-19 infection have been presented,although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data.Evidence discussing the management of HRS in highdependency care and intensive care contexts is only emerging.In this article,we provide an overview on the speculative pathophysiological me-chanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.展开更多
Objective:To explore the efficacy of earthworm’s coelomic fluid against gentamicin-induced hepatic and renal toxicity in rats.Methods:The animals were divided randomly into three groups(n=6 per group):control,gentami...Objective:To explore the efficacy of earthworm’s coelomic fluid against gentamicin-induced hepatic and renal toxicity in rats.Methods:The animals were divided randomly into three groups(n=6 per group):control,gentamicin,and Allolobophora caliginosa coelomic fluid-treated groups.Toxicity was established after injection of gentamicin daily for 8 days at a dose of 100 mg/kg.Aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase,total proteins,albumin,creatinine,urea,uric acid,malondialdehyde,glutathione,catalase and histopathology of tissues were investigated in the study.Results:Allolobophora caliginosa coelomic fluid significantly decreased urea,creatinine,uric acid,alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,and malondialdehyde levels while significantly increasing levels of total proteins,albumin,glutathione and catalase.The histopathological investigation showed partial restoration of renal and hepatic architecture.Conclusions:This study shows the potency of Allolobophora caliginosa coelomic fluid in improving the biochemical and histopathological changes induced by gentamicin in the liver and kidney of the rats.展开更多
AIM To determine the accuracy of fractional excretion of sodium(FeNa) in the diagnosis of hepatorenal syndrome(HRS). METHODS Eighty-eight liver transplantation candidates with renal dysfunction and/or proteinuria were...AIM To determine the accuracy of fractional excretion of sodium(FeNa) in the diagnosis of hepatorenal syndrome(HRS). METHODS Eighty-eight liver transplantation candidates with renal dysfunction and/or proteinuria were included in the study sample. The baseline characteristics of the patients were obtained. All the 88 patients underwent iothalamate glomerular filtration rate testing, 24-h urine collection for urinary sodium and protein excretions, random urine for sodium and creatinine testing, and percutaneous kidney biopsy. FeNa was calculated using the equation [(urine sodium × serum creatinine)/(serum sodium × urine creatinine)] × 100%. Diuretic use was recorded among the participants. Patients on renal replacement therapy were not included in the original sample.RESULTS Seventy-seven(87%) of the 88 patients had FeNa < 1%. FeNa < 1% was present in 10/10, 10/12, 11/13, 12/15 and 34/38 in patients with HRS, acute tubular necrosis, membranoproliferative glomerulonephritis, minimal histological findings(≤ 30%) and advanced(≥ 30%-40%) interstitial fibrosis and/or glomerulosclerosis, respectively(P = 0.4). FeNa < 1% was 100% sensitive and 14% specific in diagnosing HRS. Receiver operating characteristic curve confirmed the poor accuracy of FeNa < 1% in diagnosing HRS(area under the curve = 0.58, P = 0.47). Calculated positive predictive value and negative predictive value for FeNa < 1% in HRS diagnosis were 46% and 100%, respectively. When used as a continuous variable, FeNa did not correlate with kidney biopsy findings(P = 0.41). CONCLUSION FeNa < 1% was common in cirrhotic patients with renal dysfunction and it did not differentiate between HRS and other causes of renal pathologies. HRS diagnosis should be avoided in patients with FeNa > 1%.展开更多
The dying liver causes the suffocation of the kidneys,which is a simplified way of describing the pathophysiology of hepatorenal syndrome(HRS).HRS is characterized by reversible functional renal impairment due to redu...The dying liver causes the suffocation of the kidneys,which is a simplified way of describing the pathophysiology of hepatorenal syndrome(HRS).HRS is characterized by reversible functional renal impairment due to reduced blood supply and glomerular filtration rate,secondary to increased vasodilators.Over the years,HRS has gained much attention and focus among hepatologists and nephrologists.HRS is a diagnosis of exclusion,and in some cases,it carries a poor prognosis.Different classifications have emerged to better understand,diagnose,and promptly treat this condition.This targeted review aims to provide substantial insight into the epidemiology,pathophysiology,diagnosis,and management of HRS,shed light on the various milestones of this condition,and add to our current understanding.展开更多
文摘The hepatorenal syndrome(HRS)is one major extrahepatic complication of endstage liver diseases.While circulatory dysregulation is considered as primary etiology for HRS,cirrhosis-related(systemic)inflammation and/or cardial dysfunction may also play a key pathogenic role in HRS development.Exclusion of other causes of acute kidney injury(AKI)is required for diagnosis of HRS-AKI by the definition of the International Club of Ascites.However,the pathophysiology of HRS is not understood completely and there are still limited therapeutic options.Reversibility of renal dysfunction after liver transplantation indicates that HRS-AKI is a functional disorder caused by altered cellular function.The interplay between systemic inflammation and the onset of kidneyrelated hypometabolism may have a key role and needs to be studied in depth.This minireview challenges simplified views of the HRS in the context of diagnostics and therapy stressing the need for further evidence to advance the knowledge on this syndrome.
文摘Hepatorenal syndrome with acute kidney injury(HRS-AKI)is a form of rapidly progressive kidney dysfunction in patients with decompensated cirrhosis and/or acute severe liver injury such as acute liver failure.Current data suggest that HRS-AKI occurs secondary to circulatory dysfunction characterized by marked splanchnic vasodilation,leading to reduction of effective arterial blood volume and glomerular filtration rate.Thus,volume expansion and splanchnic vasoconstriction constitute the mainstay of medical therapy.However,a significant proportion of patients do not respond to medical management.These patients often require renal replacement therapy and may be eligible for liver or combined liver-kidney transplantation.Although there have been advances in the management of patients with HRS-AKI including novel biomarkers and medications,better-calibrated studies,more widely available biomarkers,and improved prognostic models are sorely needed to further improve diagnosis and treatment of HRS-AKI.
基金Supported by Natural Science Research Fund for Colleges and Universities in Jiangsu Province(No.20KJB310026)Provincial General Project of Undergraduate Innovation and Entrepreneurship Training Program(202010324055Y).
文摘[Objectives]This study was conducted to evaluate the protective effect of polysaccharides from Enteromorpha prolifera(PEP)on mice with hepatorenal syndrome induced by carbon tetrachloride.[Methods]A mouse hepatorenal syndrome model was induced by carbon tetrachloride.The serum levels of lipid,total antioxidant capacity,liver and kidney function,pathological changes of liver and kidney were selected to clarity the effectiveness of PEP on hepatorenal syndrome in mice.[Results]PEP effectively lowered the serum levels of lipid,increased total antioxidant capacity,improved liver and kidney injury,and alleviated pathological changes of liver and kidney of mice induced by carbon tetrachloride.[Conclusions]PEP has a potent preventive effect on hepatorenal syndrome induced by carbon tetrachloride in mice,which provides theoretical support for future clinical application of PEP.
文摘Hepatorenal syndrome(HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation(LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40%, respectively. In this article, we reviewed current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver alone vs simultaneous liver kidney transplant(SLKT) in transplant candidates. Many treatment options including albumin, vasoconstrictors, renal replacement therapy, and eventual LT have remained a mainstay in the treatment of HRS. Unfortunately, even after aggressive measures such as terlipressin use, the rate of recovery is less than 50% of patients. Moreover, current SLKT guidelines include:(1) estimation of glomerular filtration rate of 30 m L/min or less for 4-8 wk;(2) proteinuria > 2 g/d; or(3) biopsy proven interstitial fibrosis or glomerulosclerosis. Even with these updated criteria there is a lack of consistency regarding longterm benefits for SLKT vs LT alone. Finally, in regards to kidney dysfunction in the post-transplant setting, an estimation of glomerular filtration rate < 60 mL /min per 1.73 m2 may be associated with an increased risk of patients having long-term end stage renal disease. HRS is common in patients with cirrhosis and those on liver transplant waitlist. Prompt identification and therapy initiation in transplant candidates with HRS may improve post-transplantation outcomes. Future studies identifying optimal vasoconstrictor regimens, alternative therapies, and factors predictive of response to therapy are needed. The appropriate use of SLKT in patients with HRS remains controversial and requires further evidence by the transplant community.
文摘Acute kidney injury(AKI)in cirrhosis,including hepatorenal syndrome(HRS),is a common and serious complication in cirrhotic patients,leading to significant morbidity and mortality.AKI is separated into two categories,non-HRS AKI and HRS-AKI.The most recent definition and diagnostic criteria of AKI in cirrhosis and HRS have helped diagnose and prognosticate the disease.The pathophysiology behind non-HRS-AKI and HRS is more complicated than once theorized and involves more processes than just splanchnic vasodilation.The common biomarkers clinicians use to assess kidney injury have significant limitations in cirrhosis patients;novel biomarkers being studied have shown promise but require further studies in clinical settings and animal models.The overall management of non-HRS AKI and HRS-AKI requires a systematic approach.Although pharmacological treatments have shown mortality benefit,the ideal HRS treatment option is liver transplantation with or without simultaneous kidney transplantation.Further research is required to optimize pharmacologic and nonpharmacologic approaches to treatment.This article reviews the current guidelines and recommendations of AKI in cirrhosis.
文摘Hepatorenal syndrome(HRS) is a manifestation of extreme circulatory dysfunction and entails high morbidity and mortality.A new definition has been recently recommended by the International Club of Ascites,according to which HRS diagnosis relies in serum creatinine changes instead that on a fixed high value.Moreover,new data on urinary biomarkers has been recently published.In this sense,the use of urinary neutrophil gelatinase-associated lipocalin seems useful to identify patients with acute tubular necrosis and should be employed in the diagnostic algorithm.Treatment with terlipressin and albumin is the current standard of care.Recent data show that terlipressin in intravenous continuous infusion is better tolerated than intravenous boluses and has the same efficacy.Terlipressin is effective in reversing HRS in only 40%-50% of patients.Serum bilirubin and creatinine levels along with the increase in blood pressure and the presence of systemic inflammatory response syndrome have been identified as predictors of response.Clearly,there is a need for further research in novel treatments.Other treatments have been assessed such as noradrenaline,dopamine,transjugular intrahepatic portosystemic shunt,renal and liver replacement therapy,etc.Among all of them,liver transplant is the only curative option and should be considered in all patients.HRS can be prevented with volume expansion with albumin during spontaneous bacterial peritonitis and after post large volume paracentesis,and with antibiotic prophylaxis in patients with advanced cirrhosis and low proteins in the ascitic fluid.This manuscript reviews the recent advances in the diagnosis and management of this life-threatening condition.
文摘Terlipressin has been shown to improve both pulmonary and systemic hemodynamics in stable cirrhotic patients with pulmonary hypertension,whereas other vasoconstrictors may cause pulmonary pressures to deteriorate We investigated the pulmonary and systemic hemodynamic effects of the first terlipressin dose(2 mg) in 7 cirrhotic patients with PH presenting with variceal bleeding(n=4) or hepatorenal syndrome(n=3).Terlipressin decreased pulmonary vascular resistance(158.8±8.9 vs 186.5±13.9 dynes sec cm-5 ;P=0.003) together with an increase in systemic vascular resistance(2143± 126 vs 1643±126 dynes sec cm-5 ;P<0.001).Terlipressin should be the vasoconstrictor treatment of choice when patients present with variceal bleeding or HRS.
文摘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.
基金Chinese High Tech Research&Development(863)Program,No.2013AA020102.
文摘BACKGROUND Hepatorenal syndrome(HRS)is a severe complication of cirrhosis with high mortality,which necessitates accurate clinical decision.However,studies on prognostic factors and scoring systems to predict overall survival of HRS are not enough.Meanwhile,a multicenter cohort study with a long span of time could be more convincing.AIM To develop a novel and effective prognostic model for patients with HRS and clarify new prognostic factors.METHODS We retrospectively enrolled 1667 patients from four hospitals,and 371 eligible patients were finally analyzed to develop and validate a novel prognostic model for patients with HRS.Characteristics were compared between survivors and non-survivors,and potential prognostic factors were selected according to the impact on 28-d mortality.Accuracy in predicting 28-d mortality was compared between the novel and other scoring systems,including Model for End-Stage Liver Disease(MELD),Chronic Liver Failure-Sequential Organ Failure Assessment(CLIF-SOFA),and Chinese Group on the Study of Severe Hepatitis BAcute-on-Chronic Liver Failure(COSSH-ACLF).RESULTS Five prognostic factors,comprised of gender,international normalized ratio,mean corpuscular hemoglobin concentration,neutrophil percentage,and stage,were integrated into a new score,GIMNS;stage is a binary variable defined by the number of failed organs.GIMNS was positively correlated with MELD,CLIFSOFA,and COSSH-ACLF.Additionally,it had better accuracy[area under the receiver operating characteristic curve(AUROC):0.830]than MELD(AUROC:0.759),CLIF-SOFA(AUROC:0.767),and COSSH-ACLF(AUROC:0.759)in the derivation cohort(P<0.05).It performed better than MELD and CLIF-SOFA in the validation cohort(P<0.050)and had a higher AUROC than COSSH-ACLF(P=0.122).CONCLUSION We have developed a new scoring system,GIMNS,to predict 28-d mortality of HRS patients.Mean corpuscular hemoglobin concentration and stage were first proposed and found to be related to the mortality of HRS.Additionally,the GIMNS score showed better accuracy than MELD and CLIF-SOFA,and the AUROC was higher than that of COSSH-ACLF.
基金funded by the Deanship of Scientific Research(DSR),King Abdulaziz University,Jeddah,under grant no.(G-567-156-1439).
文摘Objective:To evaluate a novel polyherbal formulation(BSVT)containing the standardized extracts from the leaves of Boerhavia diffusa,Solidago virgaurea,Vitex negundo,and thymoquinone in CCl4 induced hepatorenal toxicity in rats.Methods:A total of 36 rats were divided into six groups including normal control,CCl4(2 mL/kg,i.p.),CCl4(2 mL/kg,i.p.)+Cystone?(750 mg/kg p.o.),CCl4(2 mL/kg,i.p.)+BSVT(25 mg/kg,p.o.),CCl4(2 mL/kg,i.p.)+BSVT(50 mg/kg,p.o.),and CCl4(2 mL/kg,i.p.)+BSVT(100 mg/kg,p.o.).All treatments were given for four weeks.Serum levels of aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,total protein,serum urea,blood urea nitrogen and creatinine were assessed.Superoxide dismutase,malondialdehyde,and glutathione peroxidase were evaluated in tissue homogenate.The histopathological study of liver and kidney tissues was also done.Results:Aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,serum urea,blood urea nitrogen and creatinine were significantly elevated(P<0.001)while total protein was considerably reduced in the CCl4 group as compared to the normal control(P<0.001),which indicated hepatorenal toxicity.In addition,superoxide dismutase and glutathione peroxidase activities were significantly decreased(P<0.001)while malondialdehyde levels were increased markedly(P<0.001).Treatment with BSVT formulation recovered these parameters towards a normal level in a dose-dependent manner.Conclusions:BSVT formulation ameliorates the hepatorenal toxicity in a dose-dependent manner.Furthermore,clinical studies are required to confirm its efficacy.
文摘AIM: To investigate clinical and biochemical features of hepatorenal syndrome(HRS), to assess short and long- term survival evaluating potential predictors of early mortality. METHODS: Sixty-two patients with liver cirrhosis and renal failure, defined as a serum creatinine value > 1.5 mg/dL on at least two measurements within 48 h, admitted to our tertiary referral Unit from 2001 to 201, were retrospectively reviewed. Among them, 33 patients(53.2%) fulfilled the revised criteria of the International Ascites Club for the diagnosis of HRS. Twenty-eight patients were treated with combinations of terlipressin and albumin, two with dopamine and al- bumin, and three with albumin alone. No patients were suitable for liver transplantation. Complete response was defined as normalization of creatinine levels to less than 1.5 mg/dL, partial response as a decrease of at least 50% but not to less than 1.5 mg/dL, no response as no reduction in creatinine or a decrease of less 50% compared to pre-treatment values. All of the patients were followed up for at least 1 year until January 2013. RESULTS: HRS type 1 was diagnosed in 15 patients(45.5%). Hepatitis C virus infection was the primary etiology(69.6%), followed by alcohol(15.2%), and cryptogenesis(15.2%). Complete response to therapy was obtained in only 3 cases(9.1%) and partial re- sponse in 7 patients(21.2%). Median survival was 30 d(range: 10-274) without significant differences be- tween type 1 and type 2 HRS. By univariate analysis, Child-Pugh class C(P = 0.009), presence of hepatocel- lular carcinoma(P = 0.04), low serum sodium(P = 0.02), high bilirubin values(P = 0.009) and high Model for End-stage Liver Disease(MELD) score(P = 0.03) were predictive factors of 30-d mortality. By multivari- ate analysis, only serum sodium < 132 mEq/L(OR = 31.39; P = 0.02) and MELD score > 27(OR = 18.72; P = 0.01) were independently associated with a survival of less than one month. CONCLUSION: HRS still has a poor prognosis, even when vasoactive drug therapies are extensively used.
文摘AIM:To develop a practical and reproducible rat model of hepatorenal syndrome for further study of the pathophysiology of human hepatorenal syndrome. METHODS:Sprague-Dawley rats were intravenously injected with D-galactosamine and lipopolysaccharide(LPS) via the tail vein to induce fulminant hepatic failure to develop a model of hepatorenal syndrome. Liver and kidney function tests and plasma cytokine levels were measured after D-galactosamine/LPS administration,and hepatic and renal pathology was studied. Glomerular filtration rate was detected in conscious rats using micro-osmotic pump technology with fluorescein isothiocyanate-labelled inulin as a surrogate marker.RESULTS:Serum levels of biochemical indicators including liver and kidney function indexes and cytokines all significantly changed,especially at 12 h after D-galactosamine/LPS administration [alanine aminotransferase,3389.5 ± 499.5 IU/L; blood urea nitrogen,13.9 ± 1.3 mmol/L; Cr,78.1 ± 2.9 μmol/L; K+,6.1 ± 0.5 mmol/L; Na+,130.9 ± 1.9 mmol/L; Cl-,90.2 ± 1.9 mmol/L; tumor necrosis factor-α,1699.6 ± 599.1 pg/m L; endothelin-1,95.9 ± 25.9 pg/m L; P < 0.05 compared with normal saline control group]. Hepatocyte necrosis was aggravated gradually,which was most significant at 12 h after treatment with D-galactosamine/LPS,and was characterized by massive hepatocyte necrosis,while the structures of glomeruli,proximal and distal tubules were normal. Glomerular filtration rate was significantly decreased to 30%-35% of the control group at 12 h after D-galactosamine/LPS administration [Glomerular filtration rate(GFR)1,0.79 ± 0.11 m L/min; GFR2,3.58 ± 0.49 m L/min·kg BW-1; GFR3,0.39 ± 0.99 m L/min·g KW-1]. The decreasing timing of GFR was consistent with that of the presence of hepatocyte necrosis and liver and kidney dysfunction.CONCLUSION:The joint use of D-galactosamine and LPS can induce liver and kidney dysfunction and decline of glomerular filtration rate in rats which is a successful rat model of hepatorenal syndrome.
基金Supported by The Sociedad Chilena de Gastroenterología(SCHGE)the Asociación Chilena de Hepatología(ACHHEP)
文摘AIM To propose several alternatives treatment of type 1 hepatorenal syndrome(HRS-1) what is the most severe expression of circulatory dysfunction on patients with portal hypertension.METHODS A group of eleven gastroenterologists and nephrologists performed a structured analysis of available literature.Each expert was designated to review and answer a question.They generated draft statements for evaluation by all the experts.Additional input was obtained from medical community.In order to reach consensus,a modified three-round Delphi technique method was used.According to United States Preventive Services Task Force criteria,the quality of the evidence and level of recommendation supporting each statement was graded.RESULTS Nine questions were formulated.The available evidence was evaluated considering its quality,number of patients included in the studies and the consistency of its results.The generated questions were answered by the expert panel with a high level of agreement.Thus,a therapeutic algorithm was generated.The role of terlipressin and norepinephrine was confirmed as the pharmacologic treatment of choice.On the other hand the use of the combination of octreotide,midodrine and albumin without vasoconstrictors was discouraged.The role of several other options was also evaluated and the available evidence was explored and discussed.Liver transplantation is considered the definitive treatment for HRS-1.The present consensus is an important effort that intends to organize the available strategies based on the available evidence in the literature,the quality of the evidence and the benefits,adverse effects and availability of the therapeutic tools described.CONCLUSION Based on the available evidence the expert panel was able to discriminate the most appropriate therapeutic alternatives for the treatment of HRS-1.
基金Supported by Natural Science Foundation of Liaoning Province,No.20170540826Science and Technology Program of Shenyang City,No.18-014-4-49Innovation Support Program of Shenyang City for Young and Middle-Aged Researchers,No.RC170051
文摘AIM To detect the expression of typeⅠ inositol 1,4,5-trisphosphate receptor(IP3 RI) in the kidney of rats with hepatorenal syndrome(HRS).METHODS One hundred and twenty-five Sprague-Dawley rats were randomly divided into four groups to receive an intravenous injection of D-galactosamine(D-Gal N) plus lipopolysaccharide(LPS; group G/L, n = 50), D-Gal N alone(group G, n = 25), LPS alone(group L, n = 25), and normal saline(group NS, n = 25), respectively.At 3, 6, 9, 12, and 24 h after injection, blood, liver, and kidney samples were collected. Hematoxylineosin staining of liver tissue was performed to assess hepatocyte necrosis. Electron microscopy was used to observe ultrastructural changes in the kidney. Western blot analysis and real-time PCR were performed to detect the expression of IP3 RI protein and m RNA in the kidney, respectively.RESULTS Hepatocyte necrosis was aggravated gradually, which was most significant at 12 h after treatment with D-galactosamine/lipopolysaccharide, and was characterized by massive hepatocyte necrosis. At the same time, serum levels of biochemical indicators including liver and kidney function indexes were all significantly changed. The structure of the renal glomerulus and tubules was normal at all time points. Western blot analysis indicated that IP3 RI protein expression began to rise at 3 h(P < 0.05) and peaked at 12 h(P < 0.01). Real-time PCR demonstrated that IP3 RI m RNA expression began to rise at 3 h(P < 0.05) and peaked at 9 h(P < 0.01).CONCLUSION IP3 RI protein expression is increased in the kidney of HRS rats, and may be regulated at the transcriptional level.
文摘BACKGROUND Hepatorenal syndrome(HRS)is a life-threatening condition among patients with advanced liver disease.Data trends specific to hospital mortality and hospital admission resource utilization for HRS remain limited.AIM To assess the temporal trend in mortality and identify the predictors for mortality among hospital admissions for HRS in the United States.METHODS We used the National Inpatient Sample database to identify an unweighted sample of 4938 hospital admissions for HRS from 2005 to 2014(weighted sample of 23973 admissions).The primary outcomes were temporal trends in mortality as well as predictors for hospital mortality.We estimated odds ratios from multilevel mixed effect logistic regression to identify patient characteristics and treatments associated with hospital mortality.RESULTS Overall hospital mortality was 32%.Hospital mortality decreased from 44%in 2005 to 24%in 2014(P<0.001),while there was an increase in the rate of liver transplantation(P=0.02),renal replacement therapy(P<0.001),length of hospital stay(P<0.001),and hospitalization cost(P<0.001).On multivariable analysis,older age,alcohol use,coagulopathy,neurological disorder,and need for mechanical ventilation predicted higher hospital mortality,whereas liver transplantation,transjugular intrahepatic portosystemic shunt,and abdominal paracentesis were associated with lower hospital mortality.CONCLUSION Although there was an increase in resource utilizations,hospital mortality among patients admitted for HRS significantly improved.Several predictors for hospital mortality were identified.
文摘There is a need to reassess the application of MELD and the impact of renal insufficiency with consideration for developing an algorithm with exception points that would lead to timely allocation of livers to patients with hepatorenal syndrome prior to occurrence of permanent renal damage without jeopardizing post-transplant survival.
文摘Coronavirus disease 2019(COVID-19)is a highly infectious disease which emerged into a global pandemic.Although it primarily causes respiratory symptoms for affected patients,COVID-19 was shown to have multi-organ manifestations.Elevated liver enzymes appear to be commonly observed during the course of COVID-19,and there have been numerous reports of liver injury secondary to COVID-19 infection.It has been established that patients with pre-existing chronic liver disease(CLD)are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD.Co-morbidities such as diabetes,hypertension,obesity,cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD,and a substantial population may also live with some degree of frailty.The mechanisms of how COVID-19 induces liver injury have been postulated.Hepatorenal syndrome(HRS)is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause,and is usually a marker of severe decompensated liver disease.Select reports of HRS following acute COVID-19 infection have been presented,although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data.Evidence discussing the management of HRS in highdependency care and intensive care contexts is only emerging.In this article,we provide an overview on the speculative pathophysiological me-chanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.
基金supported by the Deanship of Scientific Research at King Khalid University through Research Group Project under grant number(R.G.P.1–56–40)
文摘Objective:To explore the efficacy of earthworm’s coelomic fluid against gentamicin-induced hepatic and renal toxicity in rats.Methods:The animals were divided randomly into three groups(n=6 per group):control,gentamicin,and Allolobophora caliginosa coelomic fluid-treated groups.Toxicity was established after injection of gentamicin daily for 8 days at a dose of 100 mg/kg.Aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase,total proteins,albumin,creatinine,urea,uric acid,malondialdehyde,glutathione,catalase and histopathology of tissues were investigated in the study.Results:Allolobophora caliginosa coelomic fluid significantly decreased urea,creatinine,uric acid,alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,and malondialdehyde levels while significantly increasing levels of total proteins,albumin,glutathione and catalase.The histopathological investigation showed partial restoration of renal and hepatic architecture.Conclusions:This study shows the potency of Allolobophora caliginosa coelomic fluid in improving the biochemical and histopathological changes induced by gentamicin in the liver and kidney of the rats.
文摘AIM To determine the accuracy of fractional excretion of sodium(FeNa) in the diagnosis of hepatorenal syndrome(HRS). METHODS Eighty-eight liver transplantation candidates with renal dysfunction and/or proteinuria were included in the study sample. The baseline characteristics of the patients were obtained. All the 88 patients underwent iothalamate glomerular filtration rate testing, 24-h urine collection for urinary sodium and protein excretions, random urine for sodium and creatinine testing, and percutaneous kidney biopsy. FeNa was calculated using the equation [(urine sodium × serum creatinine)/(serum sodium × urine creatinine)] × 100%. Diuretic use was recorded among the participants. Patients on renal replacement therapy were not included in the original sample.RESULTS Seventy-seven(87%) of the 88 patients had FeNa < 1%. FeNa < 1% was present in 10/10, 10/12, 11/13, 12/15 and 34/38 in patients with HRS, acute tubular necrosis, membranoproliferative glomerulonephritis, minimal histological findings(≤ 30%) and advanced(≥ 30%-40%) interstitial fibrosis and/or glomerulosclerosis, respectively(P = 0.4). FeNa < 1% was 100% sensitive and 14% specific in diagnosing HRS. Receiver operating characteristic curve confirmed the poor accuracy of FeNa < 1% in diagnosing HRS(area under the curve = 0.58, P = 0.47). Calculated positive predictive value and negative predictive value for FeNa < 1% in HRS diagnosis were 46% and 100%, respectively. When used as a continuous variable, FeNa did not correlate with kidney biopsy findings(P = 0.41). CONCLUSION FeNa < 1% was common in cirrhotic patients with renal dysfunction and it did not differentiate between HRS and other causes of renal pathologies. HRS diagnosis should be avoided in patients with FeNa > 1%.
文摘The dying liver causes the suffocation of the kidneys,which is a simplified way of describing the pathophysiology of hepatorenal syndrome(HRS).HRS is characterized by reversible functional renal impairment due to reduced blood supply and glomerular filtration rate,secondary to increased vasodilators.Over the years,HRS has gained much attention and focus among hepatologists and nephrologists.HRS is a diagnosis of exclusion,and in some cases,it carries a poor prognosis.Different classifications have emerged to better understand,diagnose,and promptly treat this condition.This targeted review aims to provide substantial insight into the epidemiology,pathophysiology,diagnosis,and management of HRS,shed light on the various milestones of this condition,and add to our current understanding.
