Acute kidney injury (AKI) is commonly encountered in patients hospitalized for decompensated cirrhosis and is associated with prolonged hospital stays, increased treatment burden, and even mortality. The present study aimed to determine the prevalence of and develop a predictive nomogram for AKI in patients with decompensated cirrhosis.

This cross-sectional, double-center study involved 544 patients hospitalized with decompensated cirrhosis. Acute kidney injury was diagnosed using American Gastroenterological Association's guidelines with one more criterion: an increase in serum creatinine ≥ 0.3 mg/dL within 48 h or an increase in serum creatinine ≥ 50% compared to baseline serum creatinine or when the urine output is reduced below 0.5 mL/kg/h for > 6 h. We used the Bayesian model averaging method find the optimal model for predicting AKI. A predictive nomogram was also developed to enable risk prediction.

The overall AKI prevalence was 26.7% (95% Confidence interval [CI] 25.7-27.7). The optimal model for predicting AKI included diuretic therapy (odds ratio [OR]: 5.55; 95%CI 3.31-9.33), infection (OR: 2.06; 95%CI 1.31-3.22), ascites (OR: 3.20; 95%CT: 1.67-6.13), Child-Pugh group C (OR: 2.91; 95%CI 1.84-4.62), serum potassium (OR per 1 mmol/L increase: 1.62; 95%CI 1.25-2.1) and serum chloride (OR per 1 mmol/L decrease: 1.03; 95%CI 1.01-1.06). The area under the receiver operating characteristic curve was 0.8, with a 95%CI ranging from 0.75 to 0.84.

Acute kidney injury was relatively common among patients hospitalized for decompensated cirrhosis. A novel nomogram-including diuretic therapy, infection, ascites, Child-Pugh group C, serum potassium and, serum chloride, was helpful for the selective screening of AKI in patients with decompensated cirrhosis.

Alcohol consumption contributes to systemic organ dysfunction, but its direct effect on kidney health is unclear. Epidemiological studies show inconsistent findings due to reliance on conventional markers like serum creatinine (sCr) and blood urea nitrogen (BUN), which are insensitive to early chronic kidney disease (CKD) and influenced by factors such as muscle mass, diet, and hydration status. Experimental studies indicate that alcohol may directly exacerbate renal damage through mitochondrial dysfunction, oxidative stress, and inflammation. Furthermore, indirect effects from alcohol-induced altered intestinal permeability and microbiome, liver injury, microcirculatory/cardiac dysfunction and muscle damage may also facilitate kidney damage. Notably, alcohol-related liver disease can lead to hepatorenal syndrome, a severe form of kidney dysfunction driven by circulatory disturbances and systemic inflammation. This overview explores the adverse effects of alcohol misuse on kidney health and disease, emphasizing the need for comprehensive epidemiological studies with more sensitive kidney injury biomarkers. It also highlights the importance of using clinically relevant preclinical models to clarify the underlying mechanisms of alcohol-related kidney injury and to enhance our understanding of its long-term clinical consequences.

Renal dysfunction is common in patients undergoing liver transplant (LT) evaluation, thereby making it imperative for hepatologists to know how to diagnose, manage, and optimize treatment of acute kidney injury (AKI) and chronic kidney disease. This article reviews pre-transplant, peri-transplant, and post-transplant AKI diagnosis and management, and the role of renal replacement therapy in LT candidates.

In Ethiopia, cirrhosis is the 6th leading cause of death and is responsible for high hospitalization and mortality rates. However, until now, factors affecting in-hospital mortality of patients with liver cirrhosis are poorly understood. This study assessed the predictors of in-hospital mortality among cirrhotic patients in Ethiopia.

A retrospective cross-sectional study using data collected from the electronic medical records of patients who were admitted for complications of liver cirrhosis between January 1, 2023, and March 31, 2024, in the medical wards of Adera Medical Center, St. Paul's Hospital Millennium Medical College, and Tikur Anbessa Specialized Hospital. Frequency and cross-tabulation were used for descriptive statistics. Predictor variables with a p-value <0.25 in bivariate analyses were included in the logistic regression.

Of the 299 patients included in the final analysis, the majority (79.6%) were males, and the median age of the study participants was 45 (IQR, 36-56) years. Hepatitis B virus (32.1%) was the most common etiology, followed by alcohol (30.1%) and hepatitis C virus (13.4%). Ascites (69.2%), upper gastrointestinal bleeding (50.5%), and hepatic encephalopathy (44.8%) were the most common forms of presentation. The in-hospital mortality rate was 25.4%. West Haven grade III or IV hepatic encephalopathy (AOR: 12.0; 95% CI 2.33-61.63; P < 0.01), hepatocellular carcinoma (AOR: 9.05; 95% CI 2.18-37.14; P: 0.01), history of previous admission within one year period (AOR: 6.80; 95% CI 2.18-21.18; P < 0.01), acute kidney injury (AOR: 6.47; 95% CI 1.77-23.64; P < 0.01), and model for end-stage liver disease - sodium score (AOR: 1.17; 95% CI 1.05-1.30; P: 0.02), were found to be predictors of in-hospital mortality.

In-hospital mortality of cirrhotic patients is high in Ethiopia. West Haven grade III or IV hepatic encephalopathy is the leading cause of mortality. Hence, prompt identification and management of hepatic encephalopathy and its precipitant at an earlier stage is crucial for better treatment outcomes and survival.

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.

Patients with end-stage cirrhosis may experience renal dysfunction, necessitating a simultaneous kidney-liver transplant (SKLT). Guidelines have been put forth by the United Network for Organ Sharing (UNOS) to streamline the SKLT allocation process and ensure equitable access to transplantation. However, there is a scarcity of literature on racial and ethnic disparities in post-SKLT outcomes.

The UNOS Standard Transplant Analysis and Research Database was queried from 2005 to 2019 to study SKLT patients. Patients were stratified by race: White (reference group) recipients (n = 3513), Black recipients (n = 859), Hispanic recipients (n = 964), Asian recipients (n = 206), and other recipients (n = 85). Primary endpoints included all-cause mortality and graft failure while secondary endpoints were specific causes of death.

Hispanic recipients had a lower risk of all-cause mortality (aHR: 0.79, 95% CI: 0.68-0.93, P = 0.003), while Black recipients had a significantly increased risk of graft failure compared to Whites (aHR: 1.63, 95% CI: 1.16-2.30, P = 0.005). Evaluation of specific causes of recipient death revealed a higher risk of death due to gastrointestinal hemorrhage among Blacks (aHR: 4.16, 95% CI: 1.04-16.68, P = 0.04).

Our study findings show Black patients experience higher rates of graft failure compared to White counterparts. The reasons for these disparities are not fully understood but likely a combination of biological and social factors. Further investigation is warranted to ascertain the specific factors influencing these outcomes.

This article explores the benefits and challenges of dual organ transplants.

Simultaneous liver-kidney transplant has become a valuable option for patients with both liver and kidney failure, especially since the introduction of clearer eligibility guidelines in 2017. When done for the appropriate candidate, it can significantly improve survival and quality of life. Similarly, simultaneous pancreas-kidney transplantation provides significant advantages for patients with diabetes-related kidney failure by addressing both glycemic control and kidney function, with significant improvement in diabetes associated complications and survival.

While these procedures are complex, they offer promising solutions for managing difficult multiorgan conditions. Ongoing research and personalized patient care will be key to maximizing their benefits.

Background Invasive procedures pose a greater risk for patients with liver cirrhosis. This study investigates the impact of cirrhosis on the outcomes of implantable cardiac defibrillator (ICD) implantation. Methods We conducted a retrospective analysis using the National Readmissions Database (NRD) from 2016 to 2020. Adult patients who received an ICD, identified by the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) codes, were included. Outcomes were compared between patients with and without underlying liver cirrhosis. The primary outcome was all-cause inpatient mortality. Secondary outcomes included ischemic cerebrovascular accidents (CVA), major bleeding (gastrointestinal, intracranial, pulmonary, and other bleeding), packed red blood cell (pRBC) transfusion, pericardial complications (pericardial effusion, hemopericardium, or pericardial tamponade), acute kidney injury (AKI), acute myocardial infarction (AMI), length of stay, and total hospital charges. Results Among 264,518 patients who underwent defibrillator implantation, 3,507 patients (1.3%) had liver cirrhosis. Patients with cirrhosis experienced significantly higher inpatient mortality (adjusted odds ratio (aOR): 2.29, 95% confidence interval (CI): 1.70-3.08, P<0.001), major bleeding (aOR: 2.40, 95% CI: 1.97-2.91, P<0.001), pRBC transfusion (aOR: 2.19, 95% CI: 1.81-2.64, P<0.001), pericardial complications (aOR: 1.37, 95% CI: 1.05-1.79, P=0.02), and AKI (aOR: 1.44, 95% CI: 1.29-1.59, P<0.001). No significant difference was observed in the incidence of ischemic CVA (aOR: 0.89, 95% CI: 0.33-2.43, p=0.83), but there was a reduced incidence of AMI (aOR: 0.69, 95% CI: 0.59-0.84, P<0.001) in patients with cirrhosis. Additionally, liver cirrhosis was associated with increased hospital stays (adjusted mean difference (aMD): 2.79 days, 95% CI: 2.20-3.37, P<0.001) and higher total charges (aMD: $35,624, 95% CI: 23,698-47,549, P<0.001). Conclusion Cirrhosis is associated with increased mortality, bleeding complications, and greater resource utilization after ICD implantation. These results emphasize the need for careful evaluation when considering this procedure in patients with liver cirrhosis.

The presence of acute kidney injury (AKI) significantly increases in-hospital mortality risk for cirrhotic patients. Early prognosis prediction for these patients is crucial. We aimed to develop and validate a machine learning model for in-hospital mortality prediction for cirrhotic patients with AKI.

Data from cirrhotic patients with AKI hospitalized at the First Affiliated Hospital of Zhejiang University between January 1, 2013, and December 31, 2020 were used to train and validate an extreme Gradient Boosting model to predict in-hospital mortality risk. The Boruta algorithm was used for variable selection. The optimal model was selected and named as PHM-CPA (Prediction of in-Hospital Mortality for Cirrhotic Patients with AKI). The PHM-CPA model was then externally validated in patients from eICU Collaborative Research Database (eICU-CRD) and Medical Information Mart for Intensive Care III dataset (MIMIC). The predictive performance of PHM-CPA model was compared with that of logistic regression (LR) model and 25 previously reported models.

A total of 519 cirrhotic patients with AKI were enrolled in model training cohort, of whom 118 (23%) died during hospitalization. Fifteen variables from common laboratory tests were selected to develop the PHM-CPA model. The PHM-CPA model achieved an AUROC of 0.816 (95% CI, 0.763-0.861) in the internal validation cohort and 0.787 (95% CI, 0.745-0.830) in the external validation cohort. The PHM-CPA model consistently outperformed the LR model and 25 previously reported models.

We developed and validated the PHM-CPA model, comprising readily available clinical variables, which demonstrated superior performance and calibration in predicting in-hospital mortality for cirrhotic patients with AKI.

Background: Portal hypertension is a major complication of chronic liver diseases, leading to serious issues such as esophageal variceal bleeding. The increase in portal vein pressure is driven by both an organic component and a functional component, including tonic contraction of hepatic stellate cells. These processes result in a pathological rise in intrahepatic vascular resistance, stemming from partial impairment of hepatic microcirculation, which is further exacerbated by abnormalities in extrahepatic vessels, including increased portal blood flow. Objectives: This review aims to provide a comprehensive overview of the evolving pharmacological therapies for portal hypertension, with consideration and discussion of pathophysiological mechanisms, clinical complications, and pharmacogenetic considerations, highlighting potential directions for future research. Methods: A review of recent literature was performed to evaluate current knowledge and potential therapeutic strategies in portal hypertension. Results: For over 35 years, non-selective beta-blockers have been the cornerstone therapy for portal hypertension by reducing portal vein inflow as an extrahepatic target, effectively preventing decompensation and variceal hemorrhages. However, since not all patients exhibit an adequate response to non-selective beta-blockers (NSBBs), and some may not tolerate NSBBs, alternative or adjunctive therapies that enhance the effects of NSBBs on portal pressure are being investigated in preclinical and early clinical studies. Conclusions: A better understanding of pharmacogenetic factors and pathophysiological mechanisms could lead to more individualized and effective treatments for portal hypertension. These insights highlight potential directions for future research.

Acute kidney injury (AKI) is a frequent complication of chronic liver disease (CLD) contributing to high morbidity and mortality worldwide. While liver transplantation (LT) has shown favorable outcomes, early identification and management of AKI is imperative for survival. This review aims to highlight the epidemiology, pathophysiology, management, and prognosis of AKI in CLD.

An extensive literature search was performed using PubMed, Medline, and Google Scholar to identify literature related to epidemiology, burden, clinical presentations, prognosis, and management of AKI in CLD.

The identified studies highlighted a wide range of prevalence of AKI in hospitalized patients with CLD. The etiology and pathophysiology are multifactorial and include prerenal AKI, acute tubular injury, sepsis, gastrointestinal bleeding, bacterial translocation from the gut, and hepatorenal syndrome (HRS). AKI is associated with a higher risk of morbidity and mortality and progression to chronic kidney disease following LT. Management of AKI in CLD varies based on the underlying etiology. While vasoconstrictors like terlipressin have shown great potential in the treatment of HRS-AKI and is widely used in Europe and United States, LT remains the definitive therapy of choice. In most cases, kidney replacement therapy serves as a bridge to liver transplant.

AKI is a serious complication of CLD and early identification is essential. Diagnosis and management, particularly HRS is challenging and requires a high index of suspicion. More research is required to identify novel therapies to improve outcomes of AKI in patients with CLD.

Albumin is the most abundant protein in the human body and is synthetized exclusively by the liver. Therefore, serum albumin levels are reduced in acute and/or chronic liver disease. In cirrhosis, low levels of albumin predict the outcome. In advanced cirrhosis, the quality of albumin is decreased due to high oxidative stress and a proinflammatory state. Therefore, the administration of i.v. albumin would seem to be of pathophysiological relevance and benefit. Yet, the questions that remain are who, when, how much, and how often. While albumin infusion is recommended after large-volume paracentesis, at diagnosis of spontaneous bacterial peritonitis, in acute kidney injury, and in hepatorenal syndrome, the amount and schedule of albumin to be administered require refinement, particularly given complications related to volume overload that have become increasingly apparent. Other indications for albumin such as infections other than spontaneous bacterial peritonitis, hyponatremia, HE, prevention of poor outcomes in hospitalized, and in outpatients with cirrhosis are still debated. The results of studies in these settings are either negative, controversial, or inconclusive. This sheds some doubts regarding the use of albumin as a "one size fits all" strategy. The indication and patient selection are crucial and not always intuitive. The amount and frequency also seem to play a role in the success or failure of albumin. This review will critically discuss the evidence and underline areas where there are indications for albumin use and others where evidence is still insufficient and will have to await the development/results of randomized controlled trials.

Non-selective β blockers (NSBBs) may negatively influence renal function through decreasing heart rate and cardiac output. This study aimed to systematically investigate their association.

PubMed, EMBASE, and Cochrane library databases were searched to identify all relevant studies evaluating the association of NSBBs with renal dysfunction in cirrhotic patients. Unadjusted and adjusted data were separately extracted. Odds ratios (ORs) and hazard ratios (HRs) were pooled. Subgroup meta-analyses were performed according to the proportions of ascites and Child-Pugh class B/C and the mean model for end-stage liver disease (MELD) score. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework.

Fourteen studies were finally included. Based on unadjusted data, NSBBs significantly increased the risk of developing renal dysfunction (OR = 1.49; p = 0.03), and this association remained significant in subgroup analyses of studies where the proportions of ascites was >70% and Child-Pugh class B/C was 100%. Based on adjusted data with propensity score matching (adjusted OR = 0.61; p = 0.08) and multivariable regression modelling (adjusted HR = 0.86; p = 0.713), NSBBs did not increase the risk of developing renal dysfunction, and this association remained not significant in subgroup analyses of studies where the proportions of ascites was >70% and <70%, the proportion of Child-Pugh class B/C was <100%, and the mean MELD score was <15. The quality of evidence was very low for all meta-analyses.

NSBBs may not be associated with the development of renal dysfunction in liver cirrhosis. However, more evidence is required to clarify their association in specific populations.

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.

Acute kidney injury (AKI) frequently complicates the course of hospitalized patients with cirrhosis and negatively affects their prognosis. How AKI response influences the timing of liver transplantation (LT) remains unclear. We sought to assess the impact of AKI response to treatment on survival and LT rates in patients with cirrhosis awaiting LT. This was a retrospective multicenter study of cirrhosis patients waitlisted for LT and hospitalized with AKI in 2019. The exposure was AKI response versus no response during hospitalization. Outcomes were 90-day overall and transplant-free survival, and rates of LT with time to transplant. We adjusted for age, sex, race, cirrhosis etiology, site, and Model for End-Stage Liver Disease-Sodium (MELD-Na) score. Among the 317 patients in this study, 170 had an AKI response (53.6%), and 147 had no response (46.4%). Compared to nonresponders, responders had better 90-day overall survival (89.4% vs. 76.2%, adjusted subhazard ratio for mortality 0.34, p =0.001), and transplant-free survival (63.5% vs. 25.2%, aHR for probability of death or transplant 0.35, p <0.001). The LT rate was lower in responders (45.9% vs. 61.2%, adjusted subhazard ratio 0.55, p =0.005); 79% of transplants in responders occurred after discharge, at a median of 103 days, while 62% of transplants in nonresponders occurred during hospitalization, with the remainder occurring postdischarge at a median of 58 days. In patients with cirrhosis waitlisted for LT who are hospitalized with AKI, AKI response to therapy is associated with improved 90-day survival, despite a reduced LT rate and longer time to LT.

Background: Acute kidney injury (AKI) is one of the common complications of liver cirrhosis. It occurs in nearly 20% of patients with cirrhosis who are hospitalized. Prior literature demonstrated that the AKI occurrence in patients with cirrhosis is independently associated with higher mortality. However, there are data assessing predictors and outcomes of AKI resolution in hospitalized patients with cirrhosis. Therefore, the aim of the current study was to identify clinical predictors of AKI resolution among inpatients with cirrhosis that are easily obtained and to evaluate the clinical outcomes of those patients. Methods: The current study is a retrospective cohort of patients with cirrhosis who were hospitalized and had AKI between 2012 and 2020 at a tertiary referral center. Patients included in this study were identified using the International Classification of Diseases 9 codes and then they were manually verified by two independent chart reviewers. AKI was classified according to the AKI Network (AKIN) serum creatinine (Cr) criteria, with AKIN resolution defined as AKIN stage 1 or lower at the time of discharge, while unresolved AKIN was defined as AKIN stage 2 or 3 at the time of discharge. For univariate analysis, Fisher's exact and the two-sample T-test were utilized. For multivariable analysis, stepwise logistic regression was performed to evaluate variables associated with AKIN resolution. Survival curves were estimated and compared using the Kaplan-Meier method and Log-Rank Test. A p-value cutoff of 0.05 was used for statistical significance. Results: Between 2012 and 2020, there were 140 patients who were included (59% males). The majority of patients had viral hepatitis (54%) as the cirrhosis etiology with 80% of them having hepatitis C virus. Most patients had fluid-responsive AKI (49%), and stage 1 AKIN (69%). In terms of outcomes, the majority of patients (117 patients; 84%) had AKIN resolution at the time of discharge. In the multivariable analysis, after adjusting for clinical meaningful variables, our study shows that higher albumin value at the time of admission (adjusted Odds Ratio "aOR" = 3.28; p = 0.01) and non-metabolic dysfunction-associated steatotic liver disease (non-MASLD) cirrhosis (aOR = 9.43; p < 0.01) were variables associated with higher odds of AKIN resolution at the time of discharge. Conversely, we show that a higher Cr value at the time of admission was associated with lower odds of AKIN resolution at the time of discharge (aOR = 0.31; p < 0.01). When evaluating mortality, patients with unresolved AKIN at the time of discharge had higher rates of in-hospital mortality (p < 0.01) compared to those with resolved AKIN. Survival curve analyses using the Kaplan-Meier method indicated that patients with resolved AKIN experienced higher 90-day survival rates (p < 0.01). Additionally, those with resolved AKIN demonstrated greater transplant-free survival compared to patients with unresolved AKIN at both the 1-year (p = 0.04) and 3-year (p < 0.01) follow-ups. Conclusions: When evaluating clinical predictors of AKIN resolution in admitted patients with cirrhosis, our study showed that a higher admission albumin value and non-MASLD etiology of cirrhosis were associated with higher odds of AKIN resolution at the time of discharge. Conversely, a higher admission Cr value was associated with lower odds of AKIN resolution at the time of discharge. We also demonstrate that AKIN resolution during index admission was associated with improved short- and long-term transplant-free survival (up to 3 years). Our findings warrant external validation in larger cohorts to further evaluate the impact of inpatient AKI resolution on cirrhosis outcomes. Our findings can help clinicians predict AKIN outcomes and encourage more aggressive management of AKI, especially in high-risk patients, which can improve mortality.

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.

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.

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.

Autoimmune liver diseases (AiLD) encompass a variety of disorders that target either the liver cells (autoimmune hepatitis, AIH) or the bile ducts [(primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC)]. These conditions can progress to chronic liver disease (CLD), which is characterized by fibrosis, cirrhosis, and hepatocellular carcinoma. Recent studies have indicated a rise in hospitalizations and associated costs for CLD in the US, but information regarding inpatient admissions specifically for AiLD remains limited.

To examine the trends and mortality of inpatient hospitalization of AiLD from 2011 to 2017.

This study is a retrospective analysis utilizing the National Inpatient Sample (NIS) databases. All subjects admitted between 2011 and 2017 with a diagnosis of AiLD (AIH, PBC, PSC) were identified using the International Classification of Diseases (ICD-9) and ICD-10 codes. primary AiLD admission was defined if the first admission code was one of the AiLD codes. secondary AiLD admission was defined as having the AiLD diagnosis anywhere in the admission diagnosis (25 diagnoses). Subjects aged 21 years and older were included. The national estimates of hospitalization were derived using sample weights provided by NIS. χ 2 tests for categorical data were used. The primary trend characteristics were in-hospital mortality, hospital charges, and length of stay.

From 2011 to 2017, hospitalization rates witnessed a significant decline, dropping from 83263 admissions to 74850 admissions (P < 0.05). The patients hospitalized were predominantly elderly (median 53% for age > 65), mostly female (median 59%) (P < 0.05), and primarily Caucasians (median 68%) (P < 0.05). Medicare was the major insurance (median 56%), followed by private payer (median 27%) (P < 0.05). The South was the top geographical distribution for these admissions (median 33%) (P < 0.05), with most admissions taking place in big teaching institutions (median 63%) (P < 0.05). Total charges for admissions rose from 66031 in 2011 to 78987 in 2017 (P < 0.05), while the inpatient mortality rate had a median of 4.9% (P < 0.05), rising from 4.67% in 2011 to 5.43% in 2017. The median length of stay remained relatively stable, changing from 6.94 days (SD = 0.07) in 2011 to 6.51 days (SD = 0.06) in 2017 (P < 0.05). Acute renal failure emerged as the most common risk factor associated with an increased death rate, affecting nearly 68% of patients (P < 0.05).

AiLD-inpatient hospitalization showed a decrease in overall trends over the studied years, however there is a significant increase in financial burden on healthcare with increasing in-hospital costs along with increase in mortality of hospitalized patient with AiLD.

Optimal fluid management during major surgery is of considerable concern to anesthesiologists. Although crystalloids are the first choice for fluid management, the administration of large volumes of crystalloids is associated with poor postoperative outcomes. Albumin can be used for fluid management and may protect renal function. However, data regarding the effects of albumin administration on kidney function are conflicting. As such, the present study aimed to investigate the effect of albumin administration on renal function in patients undergoing major surgery and compare its effects with those of crystalloid fluid. The Embase, Medline, Web of Science, Cochrane Library, and KoreaMed databases were searched for relevant studies. The primary endpoint of the meta-analysis was the incidence of postoperative kidney injury, including acute kidney injury and renal replacement therapy. Twelve studies comprising 2311 patients were included; the primary endpoint was analyzed in four studies comprising 1749 patients. Perioperative albumin levels in patients undergoing major surgery did not significantly influence kidney dysfunction (p = 0.98). Postoperative fluid balance was less positive in patients who underwent major surgery and received albumin than in those who received crystalloids. Owing to the limitations of this meta-analysis, it remains unclear whether albumin administration during major surgery is better than crystalloid fluid for improving postoperative renal function.

Patients with cirrhosis are susceptible to development of acute kidney injury (AKI), which leads to poor outcome. We conducted a study to evaluate the spectrum of AKI in patients with cirrhosis.

This study was conducted in consecutive cirrhotic patients with AKI admitted in a tertiary care center of India from April 2020 to December 2022. Details including history, examination findings, and results of laboratory investigations were recorded.

A total of 243 patients were enrolled in this study. The majority (91.3%) of the patients were males. The most common etiology of cirrhosis was alcohol in 58.4% (n = 142) followed by hepatitis B in 10.3% (n = 25) of patients. Pre-renal form of AKI was present in 54.4% (n = 132) of patients and hepatorenal syndrome (HRS) in 21.8% (n = 53) of patients. IgA nephropathy was the commonest (n = 6) glomerular pathology in nonresponders with intrinsic renal disease. Majority of the patients belonged to stage II (46.9%) and stage I AKI (37%), while only 16.1% had stage III AKI. Various stages of AKI showed a significant correlation (P < 0.05) with Child-Turcotte-Pugh (CTP) score and Model for End-stage Liver Disease (MELD)-Na score. The overall in-hospital mortality rate was found to be 18.5% (n = 45).

Renal dysfunction is a frequent complication among cirrhotic patients. Pre-renal factors were the most common cause of AKI in cirrhotics. Stages of AKI showed significant correlation with liver prognostic scores. Renal biopsy should be considered in patients not responding to treatment, to guide further management.

Renal impairment (RI) is a frequent complication of liver cirrhosis and is associated with increased mortality and morbidity. Liver transplantation (LT) serves as an effective treatment method for patients with cirrhosis who have impaired renal function. However, renal function often declines after LT, influenced by various factors. This study aimed to investigate the factors contributing to RI following LT in our cases.

We analyzed the demographic data, preoperative and perioperative parameters, and postoperative outcomes of patients who underwent LT at the First Central Hospital of Mongolia from September 2011 to December 2022. Renal function was assessed by measuring the glomerular filtration rate using the Cockcroft-Gault creatinine clearance formula pretransplantation and at 24 hours, 72 hours, 7 days, 14 days, and 28 days post-LT.

Several factors increased the risk of RI among recipients. These included female sex (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.58-5.91), Child-Turcotte-Pugh (CTP) scores of B and C (OR, 4.23; 95% CI, 0.92-19.41 and OR, 7.68; 95% CI, 1.67-35.30, respectively), preoperative continuous renal replacement therapy (CRRT; OR, 5.86; 95% CI, 1.1-31.21), and a high graft-to-recipient weight ratio (GRWR; OR, 3.45; 95% CI, 1.23-9.63). Additionally, the survival rates for recipients with RI post-LT were 93.4% at 1 year and 78.1% at 3 years.

Female sex, a high CTP score, preoperative CRRT, and high GRWR were identified as risk factors for RI after LT in Mongolia.

Patients with cirrhosis and acute kidney injury (AKI) are critically ill and have high health care resource utilization (HCRU). The impact and timing of goals of care discussions on HCRU are not well described.

221 patients enrolled in a prospective cohort study of patients admitted with AKI and cirrhosis were reviewed. Documentation and timing of a goals of care discussions were analyzed as predictors of HCRU, defined as a composite outcome of intubation, initiation of renal replacement therapy, and/or admission to the intensive care unit.

Median MELD score was 26 [IQR 19, 33]. 29% patients were listed for liver transplant. 90-day mortality was 61%. 51% patients had at least one HCRU episode. Code status changed from admission to discharge from 91%/7%/0% to 68%/14%18% (full code/do not resuscitate/comfort measures, p < 0.001). 28% patients underwent goals of care discussions, with change in code status at a median of 16 [9, 22] days into admission. Only 18% of discussions were within 7 days of admission and all were after an HCRU event. Being listed for liver transplant was not associated with whether goals of care discussions occurred (23% listed vs. 31% non-listed, p = 0.24) but was associated with higher HCRU (69% vs. 43%; p < 0.001).

Goals of care discussions occurred late into the hospital course, after episodes of HCRU. Efforts should be made to engage in these discussions earlier in the hospital stay, which may decrease HCRU rates in this critically ill population and align with patients' goals of care.

The purpose of this study was to develop a nomogram for predicting in-hospital mortality in cirrhotic patients with acute kidney injury (AKI) in order to identify patients with a high risk of in-hospital death early.

This study collected data on cirrhotic patients with AKI from 2008 to 2019 using the Medical Information Mart for Intensive Care IV. Multivariate logistic regression was used to identify confounding factors related to in-hospital mortality, which were then integrated into the nomogram. The concordance index (C-Index) was used to evaluate the accuracy of the model predictions. The area under the curve (AUC) and decision curve analysis (DCA) was used to assess the predictive performance and clinical utility of the nomogram.

The final study population included 886 cirrhotic patients with AKI, and 264 (29.8%) died in the hospital. After multivariate logistic regression, age, gender, cerebrovascular disease, heart rate, respiration rate, temperature, oxygen saturation, hemoglobin, blood urea nitrogen, serum creatinine, international normalized ratio, bilirubin, urine volume, and sequential organ failure assessment score were predictive factors of in-hospital mortality. In addition, the nomogram showed good accuracy in estimating the in-hospital mortality of patients. The calibration plots showed the best agreement with the actual presence of in-hospital mortality in patients. In addition, the AUC and DCA curves showed that the nomogram has good prediction accuracy and clinical value.

We have created a prognostic nomogram for predicting in-hospital death in cirrhotic patients with AKI, which may facilitate timely intervention to improve prognosis in these patients.

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.

The purpose of this review is to describe an approach that emphasizes shared decision-making for patients with decompensated cirrhosis and acute kidney injury when liver transplantation is either not an option, or unlikely to be an option.

When acute kidney injury occurs on a background of decompensated cirrhosis, outcomes are generally poor. Providers can also be faced with prognostic uncertainty. A lack of guidance from nephrology and hepatology professional societies means that providers rely on expert opinion or institutional practice patterns.

For patients who are unlikely to receive liver transplantation, the occurrence of acute kidney injury represents an opportunity for a goals of care conversation. In this article, we share strategies through which providers can incorporate more shared decision-making when caring for these patients. The approach involves creating prognostic consensus amongst multidisciplinary teams and then relying on skilled communicators to share the prognosis. Palliative care consultation can be useful when teams need assistance in the conversations.

The concept of structural kidney damage and renal dysfunction as a result of jaundice attracted attention in the medical community in the early and mid-20th century. The postulated doctrine of the time was that the excretion of elevated concentrations of bile results in bile-stained casts occupying collecting and distal convoluted tubules, degeneration of tubular epithelium, and decreased renal function. Compared to the hepatorenal syndrome, the poster child of hepatology and nephrology collaboration, the notion of structural kidney damage and renal dysfunction as a result of cholemia lost its traction and has almost disappeared from modern textbooks. Today, cholemic nephropathy is experiencing a renaissance, with multiple case reports and case series of jaundiced patients with kidney dysfunction and evidence of bile acid casts upon histologic examination. Published cases include acute hepatitis, chronic liver injury, cirrhosis, and obstructive etiologies. Diagnosis of cholemic nephropathy is based on histological examination, typically showing intraluminal bile casts predominantly located in the distal tubules. In common bile duct-ligated mice, the histomorphological and functional alterations of cholemic nephropathy mimic those seen in humans. Some argue against the concept of cholemic nephropathy and postulate that bile casts are a secondary phenomenon. What we need are carefully designed trials to establish diagnostic criteria and subsequently translate this knowledge into evidence-based therapies.

We investigated the von Willebrand factor to ADAMTS13 ratio (von Willebrand factor [VWF]:Ag/ADAMTS13:AC) as a potential biomarker for the outcomes of acute kidney injury (AKI) in liver cirrhosis (LC).

This retrospective cross-sectional study included patients with LC who developed AKI (AKI group: n = 91) and patients with LC who did not develop AKI [non-AKI (NAKI) group, n = 91] as a control group. Plasma levels of the von Willebrand factor antigen (Ag) and ADAMTS13 activity (AC) were measured in patients with AKI or NAKI. Moreover, risk factors for onset of AKI, AKI-associated 90-day mortality, and poor AKI treatment response were identified.

The AKI group had a significantly higher VWF:Ag/ADAMTS13:AC than the NAKI group. Values of VWF:Ag/ADAMTS13:AC ≥ 5.7 were identified as risk factors for AKI onset in patients with LC (odds ratio [OR] 2.56; 95% CI 1.26-4.99; p < 0.001). Among patients with AKI, values of VWF:Ag/ADAMTS13:AC ≥ 9.0 were identified as risk factors for 90-day mortality (OR 6.83; 95% CI 2.32-20.10; p < 0.001). Cumulative survival was significantly lower in those with high (≥ 9.0) than in those with low (< 9.0) VWF:Ag/ADAMTS13:AC. Furthermore, values of VWF:Ag/ADAMTS13:AC ≥ 7.4 were identified as risk factors for poor treatment response (OR 4.2; 95% CI 1.39-12.70; p < 0.001). The treatment response rates were significantly higher in those with low (< 7.4) VWF:Ag/ADAMTS13:AC than in those with high (≥ 7.4) VWF:Ag/ADAMTS13:AC.

VWF:Ag/ADAMTS13:AC potentially predicts the onset, prognosis, and treatment response of AKI in patients with LC.

SARS-CoV-2 causes varied gastrointestinal symptoms. Cirrhosis patients face higher mortality rates from it, especially those with decompensated cirrhosis. This study examines SARS-CoV-2's impact on decompensation in previously compensated cirrhotic patients.

We analyzed the Global Collaborative Network, comprising 98 healthcare organizations across sixteen countries, using TriNetX's deidentified research database. Compensated cirrhosis patients were split into two groups: one with SARS-CoV-2-positive patients and another testing negative. Using a 1:1 propensity score matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then assessed decompensation, mortality, and GI bleed at 1 and 3 months.

Out of 252,631 identified compensated cirrhosis patients, 27.3% (69,057) tested SARS-CoV-2-positive, while 72.6% (183,574) remained negative. Post PSM, 61,963 patients were in each group. SARS-CoV-2-positive patients showed significantly higher decompensation rates (4.4% vs. 1.9% at 1 month; 6% vs. 2.6% overall). Rates of complications, like ascites, SBP, HE, and HRS, increased notably. Mortality (2.5% vs. 1.7% at 1 month; 3.6% vs. 2.7% at 3 months) and GI bleed (1.3% vs. 0.9% at 1 month; 1.9% vs. 1.2% at 3 months) were also elevated in SARS-CoV-2 patients.

SARS-CoV-2 increases decompensation over 2-fold in compensated cirrhosis patients and raises mortality and increases rates of complications at 1 and 3 months.

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) 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.

Hepatorenal syndrome (HRS) is a diagnosis of exclusion defined as acute kidney injury (AKI) with cirrhosis and ascites, with serum creatinine unresponsive to standardized volume administration and diuretic withdrawal. Persistent intravascular hypovolemia or hypervolemia may contribute to AKI and be revealed by inferior vena cava ultrasound (IVC US), which may guide additional volume management. Twenty hospitalized adult patients meeting HRS-AKI criteria had IVC US to assess intravascular volume after receiving standardized albumin administration and diuretic withdrawal. Six had IVC collapsibility index (IVC-CI) ≥50% and IVCmax ≤0.7 cm suggesting intravascular hypovolemia, 9 had IVC-CI <20% and IVCmax >0.7 cm suggesting intravascular hypervolemia, and 5 had IVC-CI ≥20% to <50% and IVCmax >0.7 cm. Additional volume management was prescribed in the 15 patients with either hypovolemia or hypervolemia. After 4-5 days, serum creatinine levels decreased ≥20% without hemodialysis in 6 of 20 patients - 3 with hypovolemia received additional volume, and 2 with hypervolemia plus one with 'euvolemia' and dyspnea were volume restricted and received diuretics. In the other 14 patients, serum creatinine failed to persistently decrease ≥20% or hemodialysis was required indicating that AKI did not improve. In summary, fifteen of 20 patients (75%) were presumed to have intravascular hypovolemia or hypervolemia by IVC ultrasound. Six of the 20 patients (40%) improved AKI by 4-5 days of follow-up with additional IVC US-guided volume management, and thus had been misdiagnosed as HRS-AKI. IVC US may more accurately define HRS-AKI as being neither hypovolemic nor hypervolemic, and guide volume management, decreasing the frequency of HRS-AKI misdiagnosis.

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.

Hepatorenal syndrome (HRS) is a critical and potentially life-threatening complication of advanced liver disease, including cirrhosis. It is characterized by the development of renal dysfunction in the absence of underlying structural kidney pathology. The pathophysiology of HRS involves complex interactions between systemic and renal hemodynamics, neurohormonal imbalances, and the intricate role of vasoconstrictor substances. Understanding these mechanisms is crucial for the timely identification and management of HRS. The diagnosis of HRS is primarily clinical and relies on specific criteria that consider the exclusion of other causes of renal dysfunction. The management of HRS comprises two main approaches: vasoconstrictor therapy and albumin infusion, which aim to improve renal perfusion and mitigate the hyperdynamic circulation often seen in advanced liver disease. Additionally, strategies such as liver transplantation and renal replacement therapy are essential considerations based on individual patient characteristics and disease severity. This review article provides a comprehensive overview of hepatorenal syndrome, focusing on its pathophysiology, diagnostic criteria, and current management strategies.

In traditional Chinese medicine (TCM), the liver is the "general organ" that is responsible for governing/maintaining the free flow of qi over the entire body and storing blood. According to the classic five elements theory, zang-xiang theory, yin-yang theory, meridians and collaterals theory, and the five-viscera correlation theory, the liver has essential relationships with many extrahepatic organs or tissues, such as the mother-child relationships between the liver and the heart, and the yin-yang and exterior-interior relationships between the liver and the gallbladder. The influences of the liver to the extrahepatic organs or tissues have been well-established when treating the extrahepatic diseases from the perspective of modulating the liver by using the ancient classic prescriptions of TCM and the acupuncture and moxibustion. In modern medicine, as the largest solid organ in the human body, the liver has the typical functions of filtration and storage of blood; metabolism of carbohydrates, fats, proteins, hormones, and foreign chemicals; formation of bile; storage of vitamins and iron; and formation of coagulation factors. The liver also has essential endocrine function, and acts as an immunological organ due to containing the resident immune cells. In the perspective of modern human anatomy, physiology, and pathophysiology, the liver has the organ interactions with the extrahepatic organs or tissues, for example, the gut, pancreas, adipose, skeletal muscle, heart, lung, kidney, brain, spleen, eyes, skin, bone, and sexual organs, through the circulation (including hemodynamics, redox signals, hepatokines, metabolites, and the translocation of microbiota or its products, such as endotoxins), the neural signals, or other forms of pathogenic factors, under normal or diseases status. The organ interactions centered on the liver not only influence the homeostasis of these indicated organs or tissues, but also contribute to the pathogenesis of cardiometabolic diseases (including obesity, type 2 diabetes mellitus, metabolic [dysfunction]-associated fatty liver diseases, and cardio-cerebrovascular diseases), pulmonary diseases, hyperuricemia and gout, chronic kidney disease, and male and female sexual dysfunction. Therefore, based on TCM and modern medicine, the liver has the bidirectional interaction with the extrahepatic organ or tissue, and this established bidirectional interaction system may further interact with another one or more extrahepatic organs/tissues, thus depicting a complex "pan-hepatic network" model. The pan-hepatic network acts as one of the essential mechanisms of homeostasis and the pathogenesis of diseases.