Acute kidney injury (AKI) is a critical and often fatal complication in decompensated cirrhosis, significantly affecting inpatient survival rates. Hepatorenal syndrome (HRS), a distinct subtype of AKI, develops in individuals with advanced cirrhosis and portal hypertension. It is marked by progressive kidney dysfunction, poor prognosis, and frequently causes death before liver transplantation. The pathogenesis of HRS involves vasodilation of the splanchnic vessels, leading to overactivation of the endogenous vasoactive systems, circulatory dysfunction, and reduced renal perfusion, which ultimately impairs glomerular filtration. Recent studies have highlighted the role of systemic inflammation in exacerbating renal damage. Despite these changes, renal histology in HRS usually shows no significant abnormalities, and there is typically no hematuria, proteinuria, or abnormal findings on ultrasound. Common risk factors for HRS include spontaneous bacterial peritonitis, infections, and large-volume paracentesis without albumin infusion. Diagnosing HRS is challenging, particularly in distinguishing it from acute tubular necrosis, due to the absence of specific biomarkers. Treatment primarily involves vasoconstrictors such as terlipressin and albumin, with liver transplantation being the definitive therapeutic option. This review provides an updated understanding of HRS, addressing its pathophysiology, diagnosis, management, and future challenges, based on recent expert consensus.

Hepatorenal Syndrome is a potentially reversible syndrome of endstage cirrhosis. It is a severe complication of cirrhosis that involves a high mortality rate and a significant economic impact on the healthcare system. This study shows the costs of the resources used for disease management and complications to be Int$14,189. Quantifying this figure contributes to an understanding of the economic impact of Hepatorenal Syndrome on patient survival.

The purpose of this study was to describe the direct medical costs incurred in Brazil for the treatment of Hepatorenal Syndrome in intensive care and intermediate therapy care units, and to investigate the impact of this syndrome on patient survival.

This longitudinal observational retrospective study included patients with Hepatorenal Syndrome admitted to the intensive and intermediate therapy care units of a public tertiary hospital. The cost generated by each patient was the sum of the direct costs and overheads.

Forty-four patients with 49 episodes of suspected Hepatorenal Syndrome were analyzed, 73% male, with a mean age of 55 years (SD= 11). Diagnosis was presumed in 21 episodes (43%), because not all of the Ascites International Club's criteria were met. Alcoholic cirrhosis was the main etiology (43%); 59% of the patients were Child-Pugh Class C at admission, with a mean (SD) model for end-stage liver disease score of 24.6 (8). Seventy-seven percent of the patients died, 32% from multiple organ failure, 29% of septic shock and 27% of hypovolemic shock. The median (IQR) of the total treatment cost for each patient was Int$14,819 (8,732-23,854). The median (IQR) length of intensive care unit stay in intensive care was 11 days (7-19). Patients with a presumed diagnosis did not have a higher hospitalization cost (p=0.249) than those with true Hepatorenal Syndrome.

The treatment of Hepatorenal Syndrome represents a significant cost, and new resource allocation in strategic areas, such as the treatment and monitoring of patients with cirrhosis, is necessary to improve their outcomes.

■ The treatment of Hepatorenal Syndrome places a huge economic burden on healthcare systems.

■ Cost analysis studies of Hepatorenal Syndrome management can help to rationally allocate resources in healthcare.

■ Timely diagnosis and management of Hepatorenal Syndrome may reduce mortality, resource utilization and costs.

Urinary biomarkers may predict acute kidney injury (AKI) in cirrhosis with ascites in a moderate volume paracentesis setting.

The study aimed to assess the risk and consequence of AKI and its progression in patients with decompensated cirrhosis undergoing paracentesis using a urine test measuring tissue inhibitor of metalloproteinases-2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7).

A randomized, controlled trial was performed. All outpatients with decompensated cirrhosis with ascites and diuretic complications were enrolled and randomized into 3 and 5 L paracentesis groups. Serial urine samples were analyzed for TIMP2. IGFBP7 concentration before and after paracentesis.

A total of 90 patients with decompensated cirrhosis were consecutively enrolled during the study period. After screening, 29 patients were enrolled in the 3-L paracentesis group, and 25 patients were enrolled in the 5-L paracentesis group. The mean of the MELD score was 8 ± 1.2. Urine TIMP2.IGFBP7 > 2, rising urine TIMP2, and rising urine TIMP2/urine Cr were shown in patients within the 5-L group for 48% (p = 0.015), 32% (p = 0.049), and 76% (p = 0.010) respectively, indicating a higher incidence of renal tubular injury markers in this group. Urine TIMP2.IGFBP7/1000 > 2 was statistically significant to predict a hemodynamic event (p = 0.002).

In cirrhotic patients with ascites undergoing paracentesis, a 5-L paracentesis volume was associated with a higher incidence of renal tubular injury markers. Trail Registration: The national clinical registration number was TCTR20191116003.

In liver cirrhosis patients, acute kidney injury (AKI) is a common and severe complication associated with significant morbidity and mortality, often leading to chronic kidney disease (CKD). This progression reflects a complex interplay of renal and hepatic pathophysiology, with AKI acting as an initiator through maladaptive repair mechanisms. These mechanisms-such as tubular cell cycle arrest, inflammatory cascades, and fibrotic processes-are exacerbated by the hemodynamic and neurohormonal disturbances characteristic of cirrhosis. Following AKI episodes, persistent kidney dysfunction or acute kidney disease (AKD) often serves as a bridge to CKD. AKD represents a critical phase in renal deterioration, characterized by prolonged kidney injury that does not fully meet CKD criteria but exceeds the temporal scope of AKI. The progression from AKD to CKD is further influenced by recurrent AKI episodes, impaired renal autoregulation, and systemic comorbidities such as diabetes and metabolic dysfunction-associated steatotic liver disease, which compound kidney damage. The clinical management of AKI and CKD in cirrhotic patients requires a multidimensional approach that includes early identification of kidney injury, the application of novel biomarkers, and precision interventions. Recent evidence underscores the inadequacy of traditional biomarkers in predicting the AKI-to-CKD progression, necessitating novel biomarkers for early detection and intervention.

Acute on chronic liver failure (ACLF) reflects the development of organ failure(s) in a patient with cirrhosis and is associated with high short-term mortality. Given that ACLF has many different 'phenotypes', medical management needs to take into account the relationship between precipitating insult, organ systems involved and underlying physiology of chronic liver disease/cirrhosis. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (e.g. infection, severe alcoholic hepatitis and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo liver transplantation or recovery. Management of these patients is complex since they are prone to develop new organ failures and infectious or bleeding complications. ICU therapy parallels that applied in the general ICU population in some complications but differs in others. Given that liver transplantation in ACLF is an emerging and evolving field, multidisciplinary teams with expertise in critical care and transplant medicine best accomplish management of the critically ill ACLF patient. The focus of this review is to identify the common complications of ACLF and to describe the proper management in critically ill patients awaiting liver transplantation in our centres, including organ support, prognostic assessment and how to assess when recovery is unlikely.

Acute kidney injury is a severe complication of cirrhosis. However, the impact of mild decreases in renal function is controversial. This study aims to evaluate the prognosis of the different stages of acute kidney injury in cirrhosis.

This is a multicenter prospective cohort study of patients hospitalized for acute decompensation of cirrhosis, with serum creatinine values measured at least twice. Primary outcome was mortality (in-hospital, 30 days, 90 days and 12 months).

Nine hundred twenty-eight patients were included in the study. Acute kidney injury was diagnosed in 505 patients (stages 1a-21.6%, 1b-27.5%, 2-28.1%, 3-22.8%). Mortality rates of patients with acute kidney injury stage 1a were significantly higher than those of individuals without acute kidney injury (in-hospital-19.3% vs 4.7%; 30-day-21.8% vs 6.7%; 90-day-35.2% vs 17.5%; 12-month-54.1% vs 37.1%; p < 0.05 for all comparisons). Mortality rates were even higher for acute kidney injury stages 1b, 2 and 3. Survival analysis demonstrated that patients without acute kidney injury performed significantly better than those with any stage of acute kidney injury (p < 0.01). Acute kidney injury stages 1a, 1b, 2 and 3 were independently associated with survival in the multivariate analysis (p < 0.01).

Patients hospitalized for acute decompensation of cirrhosis who develop acute kidney injury have significantly higher mortality rates than those who do not develop this complication. This is true even for the mildest stages of acute kidney injury (stage 1a) and remains so at different time-points, supporting recommendations for earlier treatments.

Pectin/polyacrylic acid (PPAA) hydrogel is a unique and versatile biomaterial with applications in drug delivery, wound healing, tissue engineering, and agriculture, owing to its tailored properties and multifunctional attributes. This study aims to harness the therapeutic potential of Strobilanthes urticifolia extract within a PPAA hydrogel matrix to attenuate liver and kidney fibrosis through targeted and sustained delivery of biologically active substances. PPAA hydrogel was prepared by free radical polymerization, followed by its porosity and swelling determination. The results depicted the porous nature of PPAA hydrogel and improved swelling properties at pH 7.4, confirming its drug delivery promise. The polyphenolic-enriched S. urticifolia extracts of leaf and flower were loaded onto PPAA hydrogel, and the loading efficiency was 87% (leaf) and 62.5% (flower). Moreover, slow-release studies showed controlled and prolonged release of polyphenols for 7 days. The polyphenolic-enriched hydrogel's microstructure was characterized using SEM, FTIR, and thermogravimetric analysis (TGA). SEM results revealed a highly porous structure of polyphenol enriched PPAA hydrogel, while FTIR analysis confirmed the presence of functional groups such as OH group of carboxylic acid, aliphatic CH2 stretching due to acrylic acid grafting with pectin, CO stretching due to acid linkage with pectin, CH of aromatic ring, and CH of carboxylate salt in PPAA hydrogel. TGA of PPAA hydrogel showed its stability up to 488°C. Additionally, the S. urticifolia extract loaded PPAA hydrogel displayed significant antibacterial properties and minimum inhibitory concentrations against both Gram-positive and Gram-negative bacteria. In vivo studies carried out on rats demonstrated that polyphenolic enriched PPAA hydrogel significantly attenuates liver and kidney fibrosis. Therefore, it is concluded from the present study that loading of polyphenolic enriched extract from leaves and flower of S. urticifolia enhanced the biomedical applications of PPAA hydrogel. RESEARCH HIGHLIGHTS: The PPAA hydrogel developed in this study exhibits a highly porous structure and improved swelling properties at physiological pH (7.4), making it an excellent candidate for drug delivery systems. S. urticifolia extracts, rich in polyphenols, were successfully incorporated into the PPAA hydrogel with high loading efficiencies of 87% for leaf and 62.5% for flower extracts. Loading of polyphenolic enriched extracts of S. urticifolia onto PPAA enhanced its biological activities such as antibacterial, hepatoprotective, and reno-protective activities as depicted by in vitro and in vivo studies.

Data to guide dialysis decision-making for transplant-ineligible patients with cirrhosis are lacking.

We aimed to describe the processes, predictors, and outcomes of renal replacement therapy (RRT) initiation for transplant-ineligible patients with cirrhosis at a single liver transplantation center.

We conducted a mixed-methods study of a retrospective cohort of 372 transplant-ineligible inpatients with cirrhosis with acute kidney injury (AKI) due to hepatorenal syndrome (HRS-AKI) or acute tubular necrosis (ATN) between 2008 and 2015. We performed survival analyses to evaluate 6-month survival and renal recovery and examined end-of-life care outcomes. We used a consensus-driven medical record review to characterize processes leading to RRT initiation.

We identified 266 (71.5%) patients who received RRT and 106 (28.5%) who did not receive RRT (non-RRT). Median survival was 12.5 days (RRT) vs. 2.0 days (non-RRT) (HR 0.36, 95%CI 0.28-0.46); 6-month survival was 15% (RRT) vs. 0% (non-RRT). RRT patients were more likely to die in the intensive care unit (88% vs. 32%, p < 0.001). HRS-AKI patients were more likely to be RRT dependent at 6 months than ATN patients (86% vs. 27%, p = 0.007). The most common reasons for RRT initiation were unclear etiology of AKI on presentation (32%) and belief of likely reversibility of ATN (82%).

Most transplant-ineligible patients who were initiated on RRT experienced very short-term mortality and received intensive end-of-life care. However, approximately 1 in 6 were alive at 6 months. Our findings underscore the critical need for structured clinical processes to support high-quality serious illness communication and RRT decision-making for this population.

Hepatorenal syndrome (HRS) bears a very poor prognosis with unmet need for safe and effective therapies. This systematic review and meta-analysis aimed to re-assess safety and efficacy of terlipressin versus placebo or noradrenaline for HRS, based on previous randomized controlled trials (RCTs).

PubMed, EMBASE, MEDLINE (OvidSP) and Cochrane registers were searched for trials reporting HRS treatment by terlipressin or noradrenaline. Search terms included: "hepatorenal syndrome", "terlipressin", "noradrenaline", and corresponding synonyms. Comparisons between terlipressin, noradreanaline, placebo and albumin were included. Meta-analysis was conducted for treatment response (both HRS reversal and complete response), mortality and adverse events.

15 RCTs were included, enrolling 1236 HRS patients (type 1: 1166, type 2: 70). Treatment with terlipressin+albumin resulted in significantly higher treatment response than placebo+albumin or albumin alone (risk ratio [RR]:2.75, 95% confidence interval [CI]:1.96 to 3.84; I2 = 28%, p = 0.23; n = 6). Noradrenaline was equally effective in treatment response compared to terlipressin (RR:1.19, 95% CI:0.96 to 1.46; I2 = 16%, p = 0.31; n = 7), but trials were limited by its non-blind design and small size. Sensitivity analysis showed no survival benefit with terlipressin compared to either placebo (RR:1.03, 95% CI:0.83 to 1.28; I2 = 0%, p = 0.72; n = 3) or noradreanline (RR:0.83, 95% CI:0.69 to 1.00; I2 = 4%, p = 0.39; n = 7) at 30 days of follow-up. Terlipressin carried higher risk of treatment-related adverse events compared to either placebo (RR:2.92, 95% CI:1.48 to 5.77; I2 = 0%, p = 0.75; n = 3) or noradrenaline (RR:2.45, 95% CI:1.37 to 4.37; I2 = 0%, p = 0.92; n = 5).

Terlipressin is superior to placebo, and comparable to noradreanline in treatment response, but survival benefit is lacking. Noradrenaline, with low certainty, may be a better alternative for HRS.

Acute kidney injury (AKI) occurs frequently in patients with end-stage liver disease and cirrhosis and is associated with increased short-term mortality. This study aims to study the prevalence and risk factors associated with AKI development and mortality in cirrhosis of liver patients.

In the current prospective study, hospitalized patients with liver cirrhosis from October 2021 to March 2023 were recruited. Demographic, clinical, and laboratory data were collected, which included, the etiology of cirrhosis, comorbidities, severity of liver disease, and relevant biochemical parameters. The patient was followed up for 90 days to record the clinical outcome. The statistical software SPSS was utilized to conduct the analysis.

Of 364 liver cirrhosis patients, 25.2% (n, 92) had AKI and belonged to an average age of 51.54 ± 11.82 years. The majority of individuals in the study were males (90.4%), and alcohol (63.4%) was the most common etiology of liver cirrhosis. The present study showed that higher level of direct bilirubin (p = 0.011) and MELD score (p = 0.0001) were identified as significant risk factors for AKI development in patients with liver cirrhosis. Regarding mortality, the significant risk factors were the presence of AKI (p = 0.045) and MELD score (p = 0.025). Among AKI patients, 90-day mortality rates were higher in patients with acute tubular necrosis (p value = 0.010) and stage 3 AKI (p value = 0.001).

AKI is common in cirrhosis of liver patients. Elevated levels of direct bilirubin and MELD score emerged as significant factors associated with AKI development. Furthermore, AKI and MELD scores were identified as independent risk factors for mortality at both 30 and 90 days. Survival rates were influenced by both the type and stage of AKI; AKI stage 3 and ATN patients had significantly higher mortality rate. Early AKI detection and management are crucial for reducing mortality risk in liver cirrhosis patients.

Patients with cirrhosis and clinically significant portal hypertension are at high risk of developing bacterial infections (BIs) that are the most common trigger of acute decompensation and acute-on-chronic liver failure. Furthermore, after decompensation, the risk of developing BIs further increases in an ominous vicious circle. BIs may be subtle, and they should be ruled out in all patients at admission and in case of deterioration. Timely administration of adequate empirical antibiotics is the cornerstone of treatment. Herein, we reviewed current evidences about pathogenesis, clinical implications and management of BIs in patients with cirrhosis and portal hypertension.

Acute kidney injury (AKI) is a common complication among patients with decompensated cirrhosis and its development is associated with worse prognosis in terms of survival. Patients with decompensated cirrhosis may develop a unique type of AKI, known as hepatorenal syndrome (HRS-AKI), characterized by marked impairment of kidney function due to haemodynamic changes that occur in late stages of liver cirrhosis. Besides, patients with cirrhosis also may develop chronic alterations of kidney function (chronic kidney disease, CKD), the incidence of which is increasing markedly and may be associated with clinical complications. The aim of this review is to provide the reader with an update of the most relevant aspects of alterations of kidney function in patients with cirrhossi that may be useful for theri clinical practice.

Liver transplantation (LT) has emerged as an effective therapy for severe forms of acute-on-chronic liver failure (ACLF), an entity characterized by the development of multiorgan failure and high short-term mortality. The aim of critical care management of ACLF patients is to rapidly treat precipitating events and aggressively support failing organs to ensure that patients may successfully undergo LT or, less frequently, recover. Malnutrition and sarcopenia are frequently present, adversely impacting the prognosis of these patients. Management of critical care patients with ACLF is complex and requires the participation of different specialties. Once the patient is stabilized, a rapid evaluation for salvage LT should be performed because the time window for LT is often narrow. The development of sepsis and prolonged organ support may preclude LT or diminish its chances of success. The current review describes strategies to bridge severe ACLF patients to LT, highlights the minimal evaluation required for listing and the currently suggested contraindications to proceed with LT, and addresses different aspects of management during the perioperative and early posttransplant period.

Patients with decompensated end-stage liver disease (ESLD) are at increased risk for mortality, and only liver transplantation (LT) offers meaningful hope for survival. These patients are at risk for kidney dysfunction through the continuum of care for ESLD including LT. We discuss the role of accurate estimation and measurement of baseline glomerular filtration rate in assessment of kidney dysfunction among those with ESLD. Optimizing kidney function is a vital goal in the management of these patients before LT. In this review, we summarize salient aspects of assessing and optimizing kidney function in this patient population. Precipitating factors and different causes of acute kidney injury are discussed, including hepatorenal syndrome. We further review treatment options for acute kidney injury including volume management. The role of vasopressor therapy, renal replacement therapy, and transjugular intrahepatic portosystemic shunting are discussed.

Hepatorenal syndrome (HRS) is a form of kidney dysfunction that characteristically occurs in liver cirrhosis. It is characterized by a marked impairment of kidney function in response to circulatory and hemodynamic alterations that occur in advanced stages of liver cirrhosis, aggravated by systemic inflammation and bacterial translocation. The classical definitions of the types of HRS have been recently revisited and 2 forms of HRS have been redefined: the acute form, referred to as acute kidney injury (HRS-AKI), and the chronic form, referred to as chronic kidney disease. HRS-AKI is one of the most severe forms of AKI in patients with cirrhosis and it consists of an abrupt impairment of kidney function, frequently triggered by an infection, appearing in the setting of advanced decompensated cirrhosis. Differential diagnosis with other causes of AKI is crucial because HRS-AKI requires a specific treatment. Differential diagnosis with AKI-acute tubular necrosis may be challenging and kidney biomarkers may be useful in this setting. Treatment of HRS-AKI is based on the administration of vasoconstrictor drugs in combination with volume expansion with albumin. Prognosis of HRS-AKI is poor, and the ideal definitive treatment consists of liver transplantation or simultaneous liver-kidney transplantation. HRS-AKI has a big impact on patients' quality of life. Management of HRS-AKI remains challenging in specific situations such as alcohol-associated hepatitis or metabolic-associated steatotic liver disease cirrhosis. Developing preventive measures for HRS-AKI, improving its early identification, discovering new biomarkers for differential diagnosis, and improving the response to therapy are some of the unmet needs in the field of HRS-AKI.

Hepatorenal syndrome (HRS) is a rare and highly morbid form of kidney injury unique to patients with decompensated cirrhosis. HRS is a physiologic consequence of portal hypertension, leading to a functional kidney injury that can be reversed by restoring effective circulating volume and renal perfusion. While liver transplantation is the only definitive "cure" for HRS, medical management with vasoconstrictors and i.v. albumin is a cornerstone of supportive care. Terlipressin, a V1a receptor agonist that acts on the splanchnic circulation, has been used for many years outside the United States for the treatment of HRS. However, its recent Food and Drug Administration approval has generated new interest in this population, as a new base of prescribers now work to incorporate the drug into clinical practice. In this article, we review HRS pathophysiology and diagnostic criteria, the clinical use of terlipressin and alternative therapies, and identify areas of future research in the space of HRS and kidney injury in cirrhosis.

Acute kidney injury (AKI) increases mortality in cirrhosis. Early identification of the cause of AKI helps in planning appropriate management. We aimed to find whether neutrophil gelatinase-associated lipocalin (NGAL) can be used to differentiate between different types of AKI in cirrhosis and predict short-term outcomes in patients with decompensated cirrhosis and AKI.

This was a time-bound study in which consecutive hospitalized patients with cirrhosis and AKI were prospectively recruited and managed as per standard care. Acute on chronic liver failure (ACLF) was diagnosed as per the EASL-CLIF Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) criteria. Urine NGAL was measured by enzyme-linked immunosorbent assay (ELISA) by Epitope Diagnostics Inc. kit (San Diego, USA.) in all patients on admission, and patients were followed up until hospital discharge or death.

A total of 110 consecutive patients (median [range] age: 44 [28-81] years;87.3%were male; ACLF: 71.8%; acute decompensation 28.2%; Model for end-stage liver disease (MELD) 27 [13-46]; Child-Turcotte-Pugh (CTP) 11 [7-15]) with cirrhosis and AKI were recruited. Alcohol was the most common etiology of cirrhosis(64.5%)). Pre-renal azotemia (PRA) was the most common cause of AKI (n = 56). Urine NGAL was significantly elevated in acute tubular necrosis (ATN) (1747 [6-6141] ng/ml than in hepatorenal syndrome (HRS) (379 [33.5-2320] ng/ml; P < 0.0001) and PRA (167 ng/ml [3.34-660]; P < 0.0001). Sixty-four percent patients with ATN, 27.6% patients with HRS, and none with PRA required dialysis. A total of 79.31% patients with HRS and 76% with ATN died. Urine NGAL was significantly higher in patients who required hemodialysis than in those who did not (1733 [243-6141] ng/ml vs 235 [3.34-2320] ng/ml; P < 0.0001). Both urine NGAL (n = 110) and plasma NGAL (n = 90) were significantly higher in patients who died (urine NGAL: -475 [6-6141] ng/ml vs 247 [3.34-2320] ng/ml; P = 0.002;plasma NGAL-950 [94-4859] ng/ml vs 608 [18-3300)]g/ml; P < 0.001). On multivariate analysis, urine NGAL and INR could predict mortality.

NGAL can differentiate between different types of AKI in cirrhosis and predict the need for hemodialysis and mortality in decompensated cirrhosis with AKI.

It is well known that renal dysfunction has a devastating effect on the prognosis of liver cirrhosis. In this study, the aim was to assess whether the incorporation of the kidney dysfunction type into the MELD-Na score enhances its predictive capacity for outcomes in patients awaiting liver transplantation (LT), compared to utilizing the MELD 3.0 score with albumin. In total, 2080 patients awaiting the LT were enrolled at two tertiary care institutions in Korea. Discrimination abilities were analyzed by using Harrell's c-index and iAUC values between MELD-Na-kidney dysfunction type (MELD-Na-KT) and MELD 3.0 with albumin. Clinical endpoints encompassed 3-month survival, 3-month transplant-free survival (TFS), overall survival (OS), and total TFS. Out of the total of 2080 individuals, 669 (32.16%) were male. Regarding the types of renal function impairment, 1614 (77.6%) were in the normal group, 112 (5.38%) in the AKD group, 320 (15.35%) in the CKD group, and 34 (1.63%) were in the AKD on CKD group. MELD 3.0 with albumin showed better discrimination (c-index = 0.714) compared to MELD-Na-KT (c-index = 0.708) in predicting 3-month survival. Similar results were observed for OS, 3-month TFS, and total TFS as well. When divided by sex, MELD 3.0 with albumin showed the comparable prediction of 3-month survival to MELD-Na-KT (c-index 0.675 vs. 0.671, p-value 0.221) in males. However, in the female group, MELD 3.0 with albumin demonstrated better results compared to MELD-Na-KT (c-index 0.733 vs. 0.723, p-value 0.001). The integration of kidney dysfunction types into the MELD-Na did not yield superior prognostic results compared to the MELD 3.0 score with albumin. Rather, in the female group, the MELD 3.0 score with albumin was better able to predict survival. These findings suggest that laboratory values pertaining to liver dysfunction or creatinine levels may be more significant than the type of kidney dysfunction when predicting the short-term prognosis of LT candidates.

Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.

Hepatorenal syndrome (HRS)-acute kidney injury (HRS-AKI) is a specific type of kidney injury seen in patients with cirrhosis and ascites and is associated with high mortality and morbidity. It is characterized by rapid deterioration of renal function due to reduced renal blood flow secondary to portal hypertensive splanchnic and systemic vasodilation. Early diagnosis and treatment of HRS-AKI are associated with greater likelihood of improvement in renal function, lower need for dialysis, and better post-transplant outcomes.

This review discusses the diagnostic criteria for HRS-AKI, which has undergone several key changes over the last decade, with an aim to secure an early diagnosis and aid swift treatment initiation. Additionally, this review outlines the current treatment paradigms for HRS-AKI.

In the last 20 years, there have been several advances in understanding the pathophysiology and natural course of HRS-AKI. These have led to critical changes in its definition and diagnostic algorithm. However, prognosis of HRS-AKI remains dismal with no significant improvement in HRS-AKI reversal or HRS-related mortality over this time. We discuss several gaps in the current understanding and management of HRS-AKI that will benefit from further research.

Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis.

We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other).

A total of 2,063 patients were included (median age 62 [IQR 54-69] years, 38.3% female, median MELD-Na score 26 [19-31]). The most common etiology was prerenal AKI (44.3%), followed by ATN (30.4%) and HRS-AKI (12.1%); 6.0% had other AKI, and 7.2% could not be classified. In our cohort, 8.1% of patients received a liver transplant and 36.5% died by 90 days. The lowest rate of death was observed in patients with prerenal AKI (22.2%; p <0.001), while death rates were higher but not significantly different from each other in those with HRS-AKI and ATN (49.0% vs. 52.7%; p = 0.42). Using prerenal AKI as a reference, the adjusted subdistribution hazard ratio (sHR) for 90-day mortality was higher for HRS-AKI (sHR 2.78; 95% CI 2.18-3.54; p <0.001) and ATN (sHR 2.83; 95% CI 2.36-3.41; p <0.001). In adjusted analysis, higher AKI stage and lack of complete response to treatment were associated with an increased risk of 90-day mortality (p <0.001 for all).

AKI is a severe complication of cirrhosis. HRS-AKI is uncommon and is associated with similar outcomes to ATN. The etiology of AKI, AKI stage/severity, and non-response to treatment were associated with mortality. Further optimization of vasoconstrictors for HRS-AKI and supportive therapies for ATN are needed.

Acute kidney injury (AKI) in cirrhosis carries high morbidity, and management is determined by the etiology of injury. However, a large and well-adjudicated multicenter database from US centers that uses updated AKI definitions is lacking. Our findings demonstrate that acute tubular necrosis and hepatorenal syndrome have similar outcomes (∼50% mortality at 90 days), though hepatorenal syndrome is uncommon (12% of all AKI cases). These findings represent practice patterns at US transplant/tertiary centers and can be used as a baseline, presenting the situation prior to the adoption of terlipressin in the US.

In hepatic dysfunction, renal pharmacokinetic adaptation can be observed, although information on the changes in drug exposure and the interorgan regulation of membrane transporters in kidney in liver diseases is limited. This study aimed to clarify the effects of renal exposure to nephrotoxic drugs during cholestasis induced by bile duct ligation (BDL). Among the 11 nephrotoxic drugs examined, the tissue accumulation of imatinib and cisplatin in kidney slices obtained from mice 2 weeks after BDL operation was higher than that in sham-operated mice. The uptake of imatinib in the kidney slices of BDL mice was slightly higher, whereas its efflux from the slices was largely decreased compared to that in sham-operated mice. Proteomic analysis revealed a reduction in renal expression of the efflux transporter multidrug resistance-associated protein 6 (Mrp6/Abcc6) in BDL mice, and both imatinib and cisplatin were identified as Mrp6 substrates. Survival probability after cisplatin administration was reduced in BDL mice. In conclusion, the present study demonstrated that BDL-induced cholestasis leads to the downregulation of the renal basolateral efflux transporter Mrp6, resulting in drug accumulation in renal cells and promoting drug-induced renal injury.

Acute kidney injury is considered an independent prognostic factor for mortality in patients with liver cirrhosis. Non-treated acute kidney injury can progress to hepatorenal syndrome with a poor prognosis. As suppression of tumorigenicity 2 (ST2) is a member of the interleukin-1 receptor family that aggravates inflammation and fibrotic changes in multiple organs, we measured soluble ST2 (sST2) level in the serum and urine of liver-transplant recipients at the time of transplantation. The serum sST2 level significantly increased in liver-transplant recipients with suppressed kidney function compared with that in recipients with normal function. In recipients with severely decreased liver function (model for end-stage liver disease score ≥ 30), the serum sST2 level was higher than that in recipients with preserved liver function (model for end-stage liver disease score ≤ 20, P = 0.028). The serum sST2 level in recipients with hepatorenal syndrome was higher than that in liver-transplant recipients without hepatorenal syndrome (P = 0.003). The serum sST2 level in patients with hepatorenal syndrome was higher than that in recipients without a history of acute kidney injury (P = 0.004). Recipients with hepatorenal syndrome and recovered kidney function showed higher sST2 levels than those who did not recover (P = 0.034). Collectively, an increase in the serum sST2 level reflects a decrease in both kidney and liver functions. Thus, measuring sST2 level at the time of liver transplantation can help predict renal outcomes.

Acute kidney injury (AKI) is known to be associated with increased short-term mortality among cirrhotic patients. On this background, we designed this study to evaluate various causes of AKI among admitted patients with cirrhosis of liver and predictors of 90-day mortality.

One hundred and two consecutive adult patients with cirrhosis of liver with AKI hospitalized between November 2016 and March 2018 were enrolled in this prospective study. Their detailed clinical profile, including biochemical parameters, the etiology of AKI, and their clinical outcome of survival or mortality at 90-days, were recorded.

The most common causes of AKI were infections, followed by hypovolemia, seen in 55.88% and 31.37% of the patients, respectively. Hepatorenal syndrome (HRS) was seen in 10.78%, while parenchymal renal disease was the least common (1.9%). The in-hospital mortality rate was 28.4%, while 90-day mortality was 39.21%. The HRS group had a high 90-day mortality rate of 54.54%. ROC analysis of various biochemical parameters revealed that serum creatinine (sCr), Model for End-Stage Liver Disease (MELD), International Normalized Ratio (INR), and Neutrophil-Lymphocyte ratio (NLR), followed by Child Turcotte Pugh (CTP), had high area under the curves of 0.785, 0.773, 0.747, 0.740, and 0.718, respectively, for the prediction of 90-day mortality.

Infection is the commonest cause of AKI in cirrhosis; however, mortality in patients with HRS-AKI is higher than that in those with infection-related AKI. Serum creatinine at admission, INR, NLR, and CTP scores predict short-term mortality among patients with AKI in cirrhosis. Further, large prospective studies are needed to confirm these findings.

Liver failure (LF) is characterised by a loss of the synthetic and metabolic liver function and is associated with a high mortality. Large-scale data on recent developments and hospital mortality of LF in Germany are missing. A systematic analysis and careful interpretation of these datasets could help to optimise outcomes of LF.

We used standardised hospital discharge data of the Federal Statistical Office to evaluate current trends, hospital mortality and factors associated with an unfavourable course of LF in Germany between 2010 and 2019.

A total of 62,717 hospitalised LF cases were identified. Annual LF frequency decreased from 6716 (2010) to 5855 (2019) cases and was higher among males (60.51%). Hospital mortality was 38.08% and significantly declined over the observation period. Mortality significantly correlated with patients' age and was highest among individuals with (sub)acute LF (47.5%). Multivariate regression analyses revealed pulmonary (ORARDS: 2.76, ORmechanical ventilation: 6.46) and renal complications (ORacute kidney failure: 2.04, ORhepatorenal syndrome: 2.92) and sepsis (OR: 1.92) as factors for increased mortality. Liver transplantation reduced mortality in patients with (sub)acute LF. Hospital mortality significantly decreased with the annual LF case volume and ranged from 47.46% to 29.87% in low- or high-case-volume hospitals, respectively.

Although incidence rates and hospital mortality of LF in Germany have constantly decreased, hospital mortality has remained at a very high level. We identified a number of variables associated with increased mortality that could help to improve framework conditions for the treatment of LF in the future.

Hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function, remains a major complication in patients with advanced cirrhosis, often leading to death before liver transplantation (LT). Recent updates in the pathophysiology, definition, and classification of HRS have led to a complete revision of the nomenclature and diagnostic criteria for HRS type 1, which was renamed HRS-acute kidney injury (AKI). HRS is characterized by severe impairment of kidney function due to increased splanchnic blood flow, activation of several vasoconstriction factors, severe vasoconstriction of the renal arteries in the absence of kidney histologic abnormalities, nitric oxide dysfunction, and systemic inflammation. Diagnosis of HRS remains a challenge because of the lack of specific diagnostic biomarkers that accurately distinguishes structural from functional AKI, and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The optimal treatment of HRS is LT. While awaiting LT, treatment options include vasoconstrictor drugs to counteract splanchnic arterial vasodilation and plasma volume expansion by intravenous albumin infusion. In patients with HRS unresponsive to pharmacological treatment and with conventional indications for kidney replacement therapy (KRT), such as volume overload, uremia, or electrolyte imbalances, KRT may be applied as a bridging therapy to transplantation. Other interventions, such as transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Although recently developed novel therapies have potential to improve outcomes of patients with HRS, further studies are warranted to validate the efficacy of these novel agents.

Chronic liver disease and cirrhosis contribute significantly to global mortality, with limited improvements despite medical advancements. This study aims to evaluate acute decompensation of liver cirrhosis characteristics, etiology, and survival outcomes in Oman. In addition, we examined the accuracy of prognostic scores in predicting mortality at 28 and 90 days.

We conducted a retrospective analysis of 173 adult patients with acute decompensation of liver cirrhosis at Sultan Qaboos University Hospital in Oman. We collected demographic, clinical, and biochemical data, including etiology, prognostic scores (CTP, MELD-Na, CLIF-C), and health outcomes.

Alcohol (29.5%), hepatitis C (27.75%), and hepatitis B (26.74%) were the predominant causes of liver cirrhosis in our cohort. Hepatic encephalopathy, mechanical ventilation, and admission to the intensive care unit were strongly associated with an increased mortality rate. The 1-year readmission rate stood at 42.2%. Liver transplantation was performed in 4.1% of cases. The overall mortality rate was approximately 40% during the follow-up period, and the cumulative 28-days and 90-days mortality rates were 20.8% and 25.4%, respectively. Prognostic scores (CTP, MELD-Na, CLIF-C) effectively predicted 28- and 90-day mortality, with CLIF-C demonstrating superior performance (AUROC 0.8694 ± 0.0302 for 28-day mortality and AUROC 0.8382 ± 0.0359 for 90-day mortality).

Alcohol and viral hepatitis are the leading causes of liver cirrhosis in our study. Hepatic encephalopathy is a significant predictor of poor outcomes. Prognostic scores (CTP, MELD-Na, CLIF-C) have valuable predictive abilities for short-term mortality. These findings highlight the importance of public strategies to reduce alcohol consumption and the need for the comprehensive management of liver cirrhosis in Oman. Early diagnosis and intervention can improve clinical outcomes and support the establishment of a national organ transplantation program to address the healthcare challenge effectively.

Acute kidney injury (AKI) is common in cirrhotic patients affecting almost 20% of these patients. While multiple etiologies can lead to AKI, pre-renal azotemia seems to be the most common cause of AKI. Irrespective of the cause, AKI is associated with worse survival with the poorest outcomes observed in those with hepatorenal syndrome (HRS) and acute tubular necrosis (ATN). In recent years, new definitions, and classifications of AKI in cirrhosis have emerged. More knowledge has also become available regarding the benefits and drawbacks of albumin and terlipressin use in these patients. Diagnostic tools such as urinary biomarkers and point-of-care ultrasound (POCUS) became available and they will be used in the near future to differentiate between different causes of AKI and direct management of AKI in these patients. In this update, we will review these new classifications, treatment recommendations, and diagnostic tools for AKI in cirrhotic patients.

Bacterial infections (BIs) are well-recognized precipitants of hepatic encephalopathy (HE). Nevertheless, there is a paucity of data in patients with HE associated with BI. Our aim was to describe clinical characteristics, recurrence, and prognosis of HE in patients with BI.

A prospective study with inclusion of hospitalized cirrhotic patients with BI, followed until discharge, death, or liver transplantation.

172 patients (age 57 ± 13, model of end-stage liver disease [MELD]-sodium 22 ± 8) were included. Infections were more commonly due to spontaneous bacterial peritonitis and cellulitis (22% and 23%), non-nosocomial (70%), and associated with systemic inflammatory response syndrome and septic shock in 40% and 9%, respectively. HE was diagnosed in 66 patients (grade ≥2 in 58%). In multivariate analysis, MELD-sodium, albumin, and prior HE were associated with HE at diagnosis of BI. Recurrence of HE was diagnosed in 30 patients (median 13 [interquartile range 5-22] days), more commonly manifested as overt HE (90% vs. 60% at first episode, P = 0.012) and more frequently in patients with hyponatremia (54% vs. 27% for patients without, P < 0.001). In-hospital mortality was 34% and was more common for patients with HE (51% vs. 22%, P < 0.001), irrespective of grade, and for those with recurrence (63% vs. 42%, P < 0.001). In multivariate analysis, HE at diagnosis of infection and MELD-sodium were predictors of mortality.

HE is frequent in cirrhotic patients with BI and is associated with severity of liver disease, but not with infection. These patients are at increased risk of short-term HE recurrence, especially those with hyponatremia. The presence and recurrence of HE, independent of severity, are associated with in-hospital mortality.

Kidney dysfunction is common among liver transplant candidates with decompensated cirrhosis and has a major impact on pre- and post-liver transplant survival. Updated definitions of acute kidney injury and criteria for the diagnosis of hepatorenal syndrome allow for early recognition and intervention, including early initiation of vasoconstrictor therapy for hepatorenal syndrome. The rise of the metabolic syndrome and nonalcoholic fatty liver disease as a cause of cirrhosis has coincided with an increase in intrinsic chronic kidney disease recognized in transplant candidates and recipients. Ultimately, the ability to accurately assess kidney function and associated risk is essential to decision-making in the context of transplantation, including selection of candidates for simultaneous liver and kidney transplantation.

Background: Acute kidney injury (AKI) occurs in 20-50% of patients with cirrhosis and is associated with a poor prognosis. The aim of the study is to identify the baseline factors affecting mortality in these patients at 30 and 90 days. Methods: We enrolled 117 patients with cirrhosis and AKI and followed them up prospectively. Results: Distribution of International club of ascites AKI stages was: 26 (22.03%) stage 1, 59 (50%) stage 2, and 33 (28%) stage 3. Mortalities at 30 and 90 days were 27 (22.8%) and 33 (27.9%) respectively. On multivariate analysis, variables affecting mortality at 30 days were serum creatinine level>2 mg% at 48 hours after AKI development (adjusted OR 7.93, P=0.02) and leukocytosis (total leucocyte count>11000/mm3 ) at admission (adjusted OR 6.54, P=0.002). Only leukocytosis at admission was a predictor of 90 days mortality (adjusted OR 4.76, P=0.01). Though not statistically significant, patients not responding to standard medical treatment had 3 times higher mortality at 30 days, while the maximum AKI stages (2 and 3) had eight times higher mortality at 90 days. Conclusion: In cirrhosis, AKI increases short-term mortality. High serum creatinine at 48 hours affects mortality at 30 days, while leukocytosis at baseline predicts mortality at 30 and 90 days. Progression to a higher AKI stage impacts prognosis.

Spontaneous bacterial peritonitis (SBP) is a common infection in patients with cirrhosis and ascites. Currently, the accuracy of the model for end-stage liver disease (MELD) and MELD-sodium (MELD-Na) as prognostic scores in this cohort is unclear. This study aimed to evaluate and compare the accuracy of MELD and MELD-Na for predicting 90-day mortality and determine whether the mortality risk estimates they provide accurately reflect the poor prognosis of patients with SBP Methods: Patients with cirrhosis and SBP were retrospectively identified from ascitic fluid samples sent for microscopy, culture and sensitivity analysis (1/1/18-31/12/20) and a previous audit. MELD and MELD-Na scores at diagnosis were calculated and associations with 90-day mortality were assessed using univariate analysis. Receiver operator characteristic curves were compared, and standardised mortality ratios (SMRs) were calculated by comparing the number of deaths observed to the number predicted by MELD and MELD-Na.

Of the 567 patients identified, 15 patients with cirrhosis and SBP were included. The 90-day mortality rate was 66.7% (10/15). Only concurrent hyponatremia (<135mmol/L) was associated with mortality (6/10 non-survivors vs 0/5 survivors, p=0.04). The difference in MELD and MELD-Na's C-statistic was not significant: 0.66 (95% Cl:0.35-0.98) vs 0.74 (95% Cl:0.47-1.0) respectively (p=0.72). Patients with a MELD-Na >18.5 had significantly higher 90-day mortality than patients with MELD-Na ≤18.5 (88.9% (8/9) vs. 33.3% (2/6), p=0.05). The SMR (95% Cl) for each MELD decile evaluated was 33.3 (0-79.5), 11.1 (0.2-22.0) and 3.4 (0-7.0) for scores ≤9,10-19 and 20-29 respectively. For each MELD-Na tertile, these were: 25 (0-59.6), 5.2 (0.1-10.3) and 2.7 (0.1-8.1) for scores <17,17-26, ≥27 respectively.

In a small cohort of patients with cirrhosis and SBP, the MELD's accuracy in predicting 90-day mortality was limited. MELD-Na's accuracy was higher but not significantly. Both scores consistently underestimated participants' mortality, therefore future studies could evaluate the accuracy of alternative prognostic scores in this patient group.

Hepatocirrhotic nephropathy progresses rapidly and has a poor prognosis, and early detection of renal changes in patients with cirrhosis is particularly important for its prevention and treatment. The objective of this study was to evaluate the value of shear wave elastography (SWE) in the early diagnosis of hepatocirrhotic nephropathy.

206 hepatic cirrhosis patients with normal conventional renal function were enrolled and divided into Child-Pugh grade A (Group A), Child-Pugh grade B (Group B), and Child-Pugh grade C (Group C) according to the Child-Pugh grading method. Meanwhile, 60 healthy volunteers matched in age and sex were selected as the control group. The maximum Young's modulus (Emax), average Young's modulus (Emean), and minimum Young's modulus (Emin) of the left renal parenchyma were measured by SWE in all subjects. The Emax, Emean, and Emin values of the left renal parenchyma were compared between the cirrhosis and control groups.

The Emax, Emean, and Emin values of left renal parenchyma in cirrhosis group were higher than those in control group (p = 0.00, 0.00, 0.00). The Emax, Emean, and Emin values of left renal parenchyma in cirrhosis group B and group C were higher than those in control group (p = 0.00, 0.00, 0.00; p = 0.00, 0.00, 0.00), but these values in cirrhosis group A were not significantly different from control group(p = 0.48, 0.52, 0.92). Comparison of the Emax, Emean, and Emin values in left renal parenchyma of three cirrhosis groups, the values of Group B and Group C were higher than those of Group A (p = 0.00, 0.00, 0.00; p = 0.00, 0.00, 0.00), and there was no significant difference between Group B and Group C (p = 0.71, 0.18, 0.39).

SWE can detect renal tissue damage in patients with liver cirrhosis earlier than changes identified during routine laboratory examination by quantitatively measuring the elastic parameters of renal parenchyma and may become a new method for early diagnosis of hepatorenal syndrome.

Renal failure is one of the most prevalent complications in patients with cirrhosis and is of the utmost prognostic relevance. Acute kidney injury (AKI) in cirrhosis results from a spectrum of etiologies, of which hepatorenal syndrome (HRS) carries the worst prognosis. Correct differentiation of the etiology of AKI in cirrhosis is imperative, as treatment defers substantially. This review summarizes the current diagnostic criteria, pathophysiology, diagnosis, and therapeutic concepts for AKI and HRS-AKI in cirrhosis.

Acute kidney injury (AKI) is a frequently encountered complication in decompensated chronic liver disease (CLD) with an estimated prevalence of 20%-50% among hospitalized patients. AKI often heralds the onset of a downhill course in the natural history of CLD. Serum creatinine has several limitations as a stand-alone marker of AKI in patients with decompensated CLD. The concept of hepatorenal syndrome, the prototype of AKI in decompensated CLD, has evolved tremendously over recent years. There is emerging evidence of an additional "structural" component in the pathophysiology of hepatorenal syndrome-AKI, which was previously identified as a purely "functional" form of renal impairment. Lacunae in the existent biochemical arsenal for diagnosis and prognosis of AKI have fueled enthusiastic research in the field of novel biomarkers of kidney injury in patients with cirrhosis. The advent of these biomarkers provides a crucial window of opportunity to improve the diagnosis and clinical outcomes of this vulnerable cohort of patients. This review summarizes the dynamic concept of renal dysfunction in CLD and the available literature on the role of novel biomarkers of AKI in assessing renal function, identifying AKI subtypes, and predicting prognosis. There is special emphasis on the renal tubular injury marker, neutrophil gelatinase-associated lipocalin, the most exhaustively studied biomarker of AKI in the CLD population.

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available published evidence and expert advice regarding the clinical management of patients with suspected acute kidney injury in patients with cirrhosis.

This article provides practical advice for the management of patients with cirrhosis and acute kidney injury based on the best available published evidence. This best practice document is not based on a formal systematic review. This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through the standard procedures of Clinical Gastroenterology & Hepatology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Since systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. BEST PRACTICE ADVICE 1: Acute kidney injury (AKI) should be diagnosed when the serum creatinine increases by ≥0.3 mg/dL within 48 hours or is ≥50% from baseline or when the urine output is reduced below 0.5 mL/kg/h for >6 hours. BEST PRACTICE ADVICE 2: Preventive measures against the development of AKI in cirrhosis include (1) avoidance of potentially nephrotoxic medications like nonsteroidal anti-inflammatory drugs (NSAIDs), (2) avoidance of excessive or unmonitored diuretics or nonselective beta-blockade, (3) avoidance of large-volume paracentesis without albumin replacement, and (4) counseling patients to avoid alcohol use. BEST PRACTICE ADVICE 3: (A) Investigation is directed to determining the cause of AKI, which can be due to hypovolemic causes (volume responsive, and the most common cause of AKI in patients with cirrhosis); acute tubular necrosis; hepatorenal syndrome with AKI (HRS-AKI) (a functional renal failure that persists despite volume repletion); HRS with acute kidney disease, a type of functional renal failure of <3 months- duration in which criteria for HRS-AKI are not met; or postrenal, which occurs only rarely. (B) The specific type of AKI should be identified through a careful history, physical examination, blood biochemistry, urine microscopic examination, urine chemistry (Na+ and urea) and selected urinary biomarkers, and renal ultrasound. BEST PRACTICE ADVICE 4: A rigorous search for infection is required in all patients with AKI. A diagnostic paracentesis should be carried out to evaluate for spontaneous bacterial peritonitis; blood and urine cultures and chest radiograph are also required. There is no role for routine prophylactic antibiotics in patients with AKI, but broad-spectrum antibiotics should be started whenever infection is strongly suspected. BEST PRACTICE ADVICE 5: When AKI is diagnosed, diuretics and nonselective beta-blockers should be held, NSAIDs discontinued, the precipitating cause of AKI treated, and fluid losses replaced, administering albumin 1 g/kg/d for 2 days if the serum creatinine shows doubling from baseline. Urine output, vital signs, and when indicated, echocardiography or CVP (if there is a pre-existing central line) should be used to monitor fluid status. BEST PRACTICE ADVICE 6: When the serum creatinine remains higher than twice the baseline value despite these measures, treatment of HRS-AKI should be initiated with albumin at a dose of 1 g/kg intravenously on day 1 followed by 20-40 g daily along with vasoactive agents (terlipressin; if terlipressin is not available, either a combination of octreotide and midodrine; or norepinephrine, depending on institutional preferences) and continued either until 24 hours following the return of the serum creatinine level to within ≤0.3 mg/dL of baseline for 2 consecutive days or for a total of 14 days of therapy. BEST PRACTICE ADVICE 7: Terlipressin should be initiated as a bolus dose of 1 mg every 4-6 hours (total 4-6 mg/d). The dose should be increased to a maximum of 2 mg every 4-6 hours (total 8-12 mg/d) if there is no reduction in serum creatinine at day 3 of therapy by at least 25% compared to the baseline value. Alternatively, clinicians can administer terlipressin by continuous intravenous infusion at a lower starting dose of 2 mg/d, which may reduce ischemic side effects and increase the dose gradually every 24-48 hours up to a maximum dose of 12 mg/d, or reversal of HRS. As per Food and Drug Administration restrictions, terlipressin should not be used in patients with a serum creatinine ≥5 mg/dL, or oxygen saturation of <90%. BEST PRACTICE ADVICE 8: Oral midodrine when used should be initiated at doses of 7.5 mg and titrated upward to 12.5 mg 3 times daily with octreotide (starting with 100 μg and titrating upward to 200 μg subcutaneously 3 times daily). BEST PRACTICE ADVICE 9: Norepinephrine should be used as a continuous intravenous infusion at a starting dose of 0.5 mg/h and the dose increased every 4 hours by 0.5 mg/h to a maximum of 3 mg/h with the goal of increasing the mean arterial pressure by ≥10 mm Hg and/or the urine output to >50 mL/h for at least 4 hours. BEST PRACTICE ADVICE 10: The risks of ischemic side effects of terlipressin and norepinephrine include angina and ischemia of fingers, skin, and intestine. These side effects may be lowered by starting at the lowest dose and gradually titrating upward. BEST PRACTICE ADVICE 11: Fluid status should be closely monitored because of the risk of pulmonary edema with excessive use of albumin. BEST PRACTICE ADVICE 12: Renal replacement therapy (RRT) may be used in the management of (A) AKI secondary to acute tubular necrosis; (B) HRS-AKI in potential candidates for liver transplantation (that is, RRT should not be used in patients with HRS-AKI who are not candidates for liver transplantation); and (C) AKI of uncertain etiology in which the need for RRT may be considered on an individual basis. BEST PRACTICE ADVICE 13: Transjugular intrahepatic portosystemic shunts should not be used as a specific treatment of HRS-AKI. BEST PRACTICE ADVICE 14: Liver transplantation is the most effective treatment for HRS-AKI. Pharmacotherapy for HRS-AKI before proceeding with liver transplantation may be associated with better post-liver transplantation outcomes. Selected patients with HRS-AKI may require simultaneous liver kidney transplantation based on updated Organ Procurement and Transplantation Network listing criteria.

AKI is commonly encountered in patients with decompensated cirrhosis, and it is associated with unfavorable outcomes. Among factors specific to cirrhosis, hepatorenal syndrome type 1, also referred to as hepatorenal syndrome-AKI, is the most salient and unique etiology. Patients with cirrhosis are vulnerable to traditional causes of AKI, such as prerenal azotemia, acute tubular injury, and acute interstitial nephritis. In addition, other less common etiologies of AKI specifically related to chronic liver disease should be considered, including abdominal compartment syndrome, cardiorenal processes linked to cirrhotic cardiomyopathy and portopulmonary hypertension, and cholemic nephropathy. Furthermore, certain types of GN can cause AKI in cirrhosis, such as IgA nephropathy or viral hepatitis related. Therefore, a comprehensive diagnostic approach is needed to evaluate patients with cirrhosis presenting with AKI. Management should be tailored to the specific underlying etiology. Albumin-based volume resuscitation is recommended in prerenal AKI. Acute tubular injury and acute interstitial nephritis are managed with supportive care, withdrawal of the offending agent, and, potentially, corticosteroids in acute interstitial nephritis. Short of liver transplantation, vasoconstrictor therapy is the primary treatment for hepatorenal syndrome type 1. Timing of initiation of vasoconstrictors, the rise in mean arterial pressure, and the degree of cholestasis are among the factors that determine vasoconstrictor responsiveness. Large-volume paracentesis and diuretics are indicated to relieve intra-abdominal hypertension and renal vein congestion. Direct-acting antivirals with or without immunosuppression are used to treat hepatitis B/C-associated GN. In summary, AKI in cirrhosis requires careful consideration of multiple potentially pathogenic factors and the implementation of targeted therapeutic interventions.

Acute kidney injury (AKI) is a frequent complication in patients with cirrhosis that is associated with poor outcomes and decreased survival. The definition of AKI in cirrhosis is currently based on changes of serum creatinine levels with respect to baseline values. Differential diagnosis of the causes of AKI is of major relevance, considering that some causes of AKI, such as hepatorenal syndrome, have specific treatment options and different prognosis. Prediction of kidney function recovery and patients' survival is also crucial in this patient population to guide clinical decisions. AKI biomarkers in cirrhosis have emerged as a promising tool for differential diagnosis and prognosis in this situation. There are consistent data showing that some urine biomarkers, particularly neutrophil gelatinase-associated lipocalin, may be useful in daily clinical practice for the differential diagnosis of the cause of AKI in cirrhosis. AKI biomarkers may constitute a useful tool for use in differential diagnosis, prognosis of renal function, and survival in patients with cirrhosis. This review focuses on the current state of knowledge and future perspective of novel biomarkers of AKI in cirrhosis.

Renal dysfunction often complicates the course of liver disease, resulting in higher morbidity and mortality. The accurate assessment of kidney function in these patients is essential to early identify, stage and treat renal impairment as well as to better predict the prognosis, prioritize the patients for liver transplantation and decide whether to opt for simultaneous liver-kidney transplants. This review analyses the available tools for direct or indirect assessment of glomerular filtration rate, focusing on the flaws and strengths of each method in the specific setting of cirrhosis. The aim is to deliver a clear-cut view on this complex issue, trying to point out which strategies to prefer in this context, especially in the peculiar setting of liver transplantation. Moreover, a glance is given at future promising tools for glomerular filtration rate assessment, including new biomarkers and new equations specifically modelled for the cirrhotic population.