• End-stage renal disease
• Hypothermic machine perfusion
• Liver transplantation
• Simultaneous liver-kidney transplantation

• Humans
• Liver Transplantation
• Kidney Transplantation/methods
• Organ Preservation/methods
• Forecasting
• Graft Survival

• Université Toulouse III - Paul Sabatier

• Hepatorenal syndrome
• cirrhosis
• end-stage liver disease
• renal failure
• review

• Hepatorenal Syndrome/therapy
• Hepatorenal Syndrome/etiology
• Hepatorenal Syndrome/epidemiology
• Hepatorenal Syndrome/diagnosis
• Humans
• Liver Cirrhosis/complications
• Liver Cirrhosis/epidemiology
• Liver Cirrhosis/therapy
• Vasoconstrictor Agents/therapeutic use
• Vasoconstrictor Agents/adverse effects

• Acute Kidney Injury
• Cirrhosis
• Liver Transplant
• Metabolomics
• Mortality
• Proteomics

• K24 AG080021 NIA NIH HHS
• P30 DK026743 NIDDK NIH HHS
• L30 DK133959 NIDDK NIH HHS
• K23 DK128567 NIDDK NIH HHS
• R01 AG059183 NIA NIH HHS
• K23 DK131278 NIDDK NIH HHS

• Acute kidney injury
• Cholemic
• Cirrhosis
• Congestive
• Decompensated
• HRS-1
• HRS-AKI
• Hemodynamic
• Renal vasoconstriction

• Humans
• Hepatorenal Syndrome/physiopathology
• Hepatorenal Syndrome/therapy
• Hepatorenal Syndrome/etiology
• Liver Cirrhosis/physiopathology
• Liver Cirrhosis/complications
• Renal Circulation/physiology
• Hemodynamics/physiology
• Renin-Angiotensin System/physiology
• Kidney/physiopathology
• Hypertension, Portal/physiopathology
• Ascites/physiopathology

• Acute kidney injury
• Biomarkers
• Hepatorenal syndrome
• NGAL
• Terlipressin

• Humans
• Hepatorenal Syndrome/diagnosis
• Hepatorenal Syndrome/therapy
• Hepatorenal Syndrome/etiology
• Biomarkers/urine
• Terlipressin/therapeutic use
• Lypressin/analogs & derivatives
• Lypressin/therapeutic use
• Vasoconstrictor Agents/therapeutic use
• Diagnosis, Differential
• Lipocalin-2/urine
• Acute Kidney Injury/diagnosis
• Acute Kidney Injury/therapy

• cirrhosis
• liver failure
• renal failure
• portal hypertension
• dialysis
• renal replacement therapy
• vasoconstrictor
• liver transplantation

• K23 DK128567 NIDDK NIH HHS
• K23 DK131278 NIDDK NIH HHS
• L30 DK133959 NIDDK NIH HHS

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.

• Hepatorenal syndrome
• Pathophysiology
• Diagnosis
• Management
• Review

The hepatorenal syndrome (HRS) is one major extrahepatic complication of end-stage 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 kidney-related 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.

• Hepatorenal syndrome
• Liver disease
• Cirrhosis
• Inflammation
• Chronic kidney disease
• Acute kidney injury

In cirrhosis with ascites, hepatorenal syndrome (HRS) is a specific prerenal dysfunction unresponsive to fluid volume expansion. Acute-on-chronic liver failure (ACLF) comprises a group of clinical syndromes with multiple organ failure and early high mortality. There are differences in the characterization of ACLF between the Eastern and Western medical communities. Patients with ACLF and acute kidney injury (AKI) have more structural injuries, contributing to confusion in diagnosing HRS-AKI. In this review, we discuss progress in the pathogenesis, diagnosis, and management of HRS-AKI, especially in patients with ACLF. Controversy regarding HRS-AKI in ACLF and acute liver failure, hepatic carcinoma, shock, sepsis, and chronic kidney disease is also discussed. Research on the treatment of HRS-AKI with ACLF needs to be more actively pursued to improve disease prognosis.

• acute kidney injury
• acute-on-chronic liver failure
• hepatorenal syndrome
• review

• acute kidney injury
• ascites
• bile nephrosis
• hepatorenal syndrome
• liver failure

• Biomarkers
• Hepatorenal Syndrome/diagnosis
• Hepatorenal Syndrome/physiopathology
• Hepatorenal Syndrome/therapy
• Humans
• Risk Factors

To analyze the impact of acute-on-chronic liver failure (ACLF) immediately before liver transplantation (LT) on short-term kidney function.

As end-stage liver disease progresses, renal blood flow linearly correlates with mean arterial blood pressure (MBP) due to impaired autoregulation. We investigated whether the lower degree of postoperative MBP would predict the occurrence of postoperative acute kidney injury (AKI) after liver transplantation.

This retrospective study enrolled 1,136 recipients with normal preoperative kidney function. Patients were categorized into two groups according to the averaged postoperative MBP: <90 mmHg (MBP_below90) and ≥90 mmHg (MBP_over90). The primary endpoint was occurrence of postoperative AKI, defined by the creatinine criteria of the Kidney Disease Improving Global Outcomes. The logistic regression model with inverse probability treatment weighting (IPTW) of propensity score was used to compare the risk of postoperative AKI between two groups.

MBP_below90 group (83.0±5.1 mmHg) showed higher prevalence and risk of postoperative AKI (74.2% versus 62.6%, p<0.001; IPTW-OR 1.34 [1.12–1.61], p=0.001) compared with MBP_over90 group (97.3±5.2 mmHg). When stratified by quartiles of baseline cystatin C glomerular filtration ratio (GFR), the association between MBP_below90 and postoperative AKI remained significant only with the lowest quartile (cystatin C GFR ≤85 mL/min/1.73 m²; IPTW-OR 2.24 [1.53–3.28], p<0.001), but not with 2^nd–4^th quartiles.

Our results suggest that maintaining supranormal MBP over 90 mmHg may be beneficial to reduce the risk of post-LT AKI, especially for liver transplant recipients with cystatin C GFR ≤85 mL/min/1.73 m².

• ACLF
• acute kidney injury
• cirrhosis
• hepatorenal syndrome

• Acute Kidney Injury/diagnosis
• Acute Kidney Injury/epidemiology
• Acute Kidney Injury/etiology
• Acute Kidney Injury/therapy
• Acute-On-Chronic Liver Failure/complications
• Acute-On-Chronic Liver Failure/therapy
• Animals
• Biomarkers/analysis
• Disease Models, Animal
• Hemoperfusion
• Hepatorenal Syndrome/diagnosis
• Hepatorenal Syndrome/epidemiology
• Hepatorenal Syndrome/etiology
• Hepatorenal Syndrome/therapy
• Humans
• Incidence
• Kidney/pathology
• Kidney/physiopathology
• Liver/physiopathology
• Liver Cirrhosis/complications
• Liver Cirrhosis/therapy
• Liver Transplantation
• Prognosis
• Severity of Illness Index
• Vasoconstrictor Agents/therapeutic use

Simultaneous liver-kidney (SLK) transplantation plays an important role in treating kidney failure in patients with end-stage liver disease. It used 5% of deceased donor kidney transplanted in 2015. We evaluated the utility, defined as posttransplant kidney allograft lifespan, of this practice.

Using data from the Scientific Registry of Transplant Recipients, we compared outcomes for all SLK transplants between January 1, 1995, and December 3, 2014, to their donor-matched kidney used in kidney-alone (Ki) or simultaneous pancreas kidney (SPK) transplants. Primary outcome was kidney allograft lifespan, defined as the time free from death or allograft failure. Secondary outcomes included death and death-censored allograft failure. We adjusted all analyses for donor, transplant, and recipient factors.

The adjusted 10-year mean kidney allograft lifespan was higher in Ki/SPK compared with SLK transplants by 0.99 years in the Model for End-stage Liver Disease era and 1.71 years in the pre-Model for End-stage Liver Disease era. Death was higher in SLK recipients relative to Ki/SPK recipients: 10-year cumulative incidences 0.36 (95% confident interval 0.33-0.38) versus 0.19 (95% confident interval 0.17-0.21).

SLK transplantation exemplifies the trade-off between the principles of utility and medical urgency. With each SLK transplantation, about 1 year of allograft lifespan is traded so that sicker patients, that is, SLK transplant recipients, are afforded access to the organ. These data provide a basis against which benefits derived from urgency-based allocation can be measured.

This analysis of the UNOS data demonstrated that SLK patients had decreased long term renal graft function that SPK patients. This analysis demonstrates the difficult policy choices epitomized by prioritizing the SLK population and its impact of utility considerations. Supplemental digital content is available in the text.

To determine the accuracy of fractional excretion of sodium (FeNa) in the diagnosis of hepatorenal syndrome (HRS).

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.

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).

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%.

• Fractional excretion of sodium
• Hepatorenal syndrome
• Renal dysfunction
• Liver transplantation
• Urinary sodium excretion
• Accuracy

• acute kidney injury
• inflammation
• ischemia reperfusion
• sepsis

Acute renal impairment is common in patients with chronic liver disease, occurring in approximately 19% of hospitalised patients with cirrhosis. A variety of types of renal impairment are recognised. The most important of these is the hepatorenal syndrome, a functional renal impairment due to circulatory and neurohormonal abnormalities that underpin cirrhosis. It is one of the most severe complications of cirrhosis with survival often measured in weeks to months. A variety of treatment options exist with early diagnosis and appropriate treatment providing the best hope for cure. This paper provides a comprehensive and up-to-date review of hepatorenal syndrome and lays out the topic according to the following sections: pathophysiology, historical developments, diagnostic criteria and limitations, epidemiology, precipitating factors, predictors, clinical and laboratory findings, prognosis, treatment options, prophylaxis, and conclusion.

Cirrhosis results from progressive fibrosis and is the final outcome of all chronic liver disease. It is among the ten leading causes of death in United States. Cirrhosis can result in portal hypertension and/or hepatic dysfunction. Both of these either alone or in combination can lead to many complications, including ascites, varices, hepatic encephalopathy, hepatocellular carcinoma, hepatopulmonary syndrome, and coagulation disorders. Cirrhosis and its complications not only impair quality of life but also decrease survival. Managing patients with cirrhosis can be a challenge and requires an organized and systematic approach. Increasing physicians’ knowledge about prevention and treatment of these potential complications is important to improve patient outcomes. A literature search of the published data was performed to provide a comprehensive review regarding the management of cirrhosis and its complications.

• Ascites
• Hepatic encephalopathy
• Portal hypertension
• Varices
• Portopulmonary hypertension
• Hepatopulmonary syndrome

• Ascites/etiology
• Ascites/therapy
• Bacterial Infections/microbiology
• Bacterial Infections/therapy
• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/therapy
• Esophageal and Gastric Varices/etiology
• Esophageal and Gastric Varices/therapy
• Evidence-Based Medicine
• Hepatic Encephalopathy/etiology
• Hepatic Encephalopathy/therapy
• Hepatopulmonary Syndrome/etiology
• Hepatopulmonary Syndrome/therapy
• Hepatorenal Syndrome/etiology
• Hepatorenal Syndrome/therapy
• Humans
• Hypertension, Portal/etiology
• Hypertension, Portal/therapy
• Hyponatremia/etiology
• Hyponatremia/therapy
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/etiology
• Liver Cirrhosis/mortality
• Liver Cirrhosis/therapy
• Liver Neoplasms/etiology
• Liver Neoplasms/therapy
• Peritonitis/microbiology
• Peritonitis/therapy
• Risk Factors
• Treatment Outcome

• cirrhosis
• acute kidney injury
• ngal
• il-18
• hepatorenal syndrome

• Acute Kidney Injury/urine
• Acute-Phase Proteins/urine
• Biomarkers/urine
• Cross-Sectional Studies
• Female
• Humans
• Interleukin-18/urine
• Kidney Function Tests
• Lipocalin-2
• Lipocalins/urine
• Liver Cirrhosis/urine
• Liver Function Tests
• Male
• Middle Aged
• Proto-Oncogene Proteins/urine

• Acute renal failure
• Hepatic failure
• Immunosuppression
• Liver transplant

• acute kidney injury
• biomarker
• cirrhosis
• hepatorenal syndrome
• ngal
• mortality

• Adolescent
• Adult
• Aged
• Databases, Factual
• Female
• Graft Survival
• Humans
• Kidney Transplantation/methods
• Liver Failure/mortality
• Liver Failure/therapy
• Liver Transplantation/methods
• Male
• Middle Aged
• Postoperative Complications
• Renal Insufficiency/mortality
• Renal Insufficiency/therapy
• Risk
• Risk Factors
• Tissue and Organ Procurement
• Treatment Outcome

• 1UL1RR031973 NCRR NIH HHS
• R01 CA054706-07 NCI NIH HHS
• UL1 RR031973-01 NCRR NIH HHS
• R01 CA054706 NCI NIH HHS
• UL1 RR031973 NCRR NIH HHS

Hepatorenal syndrome (HRS) is a reversible form of functional renal failure that occurs with advanced hepatic cirrhosis and liver failure. Despite mounting research in HRS, its etiology and medical therapy has not been resolved. HRS encompasses 2 distinct types. Type 1 is characterized by the rapid development of renal failure that occurs within 2 wk and involves a doubling of initial serum creatinine. Type 2 has a more insidious onset and is often associated with ascites. Animal studies have shown that both forms, in particular type 1 HRS, are often precipitated by bacterial infections and circulatory changes. The prognosis for HRS remains very poor. Type 1 and 2 both have an expected survival time of 2 wk and 6 mo, respectively. Progression of liver cirrhosis and the resultant portal hypertension leads to the pooling of blood in the splanchnic vascular bed. The ensuing hyperdynamic circulation causes an ineffective circulatory volume which subsequently activates neurohormonal systems. Primarily the sympathetic nervous system and the renin angiotensin system are activated, which, in the early stages of HRS, maintain adequate circulation. Both advanced cirrhosis and prolonged activation of neurohormonal mechanisms result in fatal complications. Locally produced nitric oxide may have the potential to induce a deleterious vasodilatory effect on the splanchnic circulation. Currently medical therapy is aimed at reducing splanchnic vasodilation to resolve the ineffective circulation and maintain good renal perfusion pressure. Terlipressin, a vasopressin analogue, has shown potential benefit in the treatment of HRS. It prolongs both survival time and has the ability to reverse HRS in the majority of patients. In this review we aim to focus on the pathogenesis of HRS and its treatment with terlipressin vs other drugs.

• Heptorenal syndrome
• Terlipressin
• Kidney
• Liver

• Adult
• Alcoholism/complications
• Creatinine/blood
• Female
• Hepatitis B/complications
• Hepatitis C/complications
• Hepatorenal Syndrome/etiology
• Hepatorenal Syndrome/surgery
• Humans
• Kidney/injuries
• Liver Transplantation/methods
• Liver Transplantation/physiology
• Male
• Middle Aged
• Renal Dialysis
• Retrospective Studies
• Treatment Outcome