Acute Kidney Injury In Cirrhotic Patients Research Articles

Value of Urinary NGAL for Predicting Acute Kidney Injury Secondary to Decompensated Cirrhosis

Abstract Background Physicians caring for patients with cirrhosis should recognize the acute or chronic character of renal disease; the causes of renal injury; the clinical conditions leading concomitantly to acute kidney injury (AKI) and liver dysfunction, and the prognostic factors associated with the progression of AKI. Hypovolemia (due to diuretics, hemorrhage, diarrhea), acute tubular necrosis, sepsis, nephrotoxic agents (such as non steroidal anti-inflammatory drugs, aminoglycosides radiological contrasts) and hepatorenal syndrome-type 1 are the most common causes of AKI in cirrhotic patients. Aim of the Work The aim of this study was to evaluate urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) as a diagnostic biomarker for different causes of acute kidney injury in liver cirrhosis. Patients and Methods This was a cross sectional study done in patients with liver cirrhosis hospitalized at the Gastroenterology Department of the Ain shams university hospital. Results We found that in the comparison between HRS and AKI regarding HB, WBCs, Platelets, ALT, AST, Albumin, INR, Bilirubin, Urea, Creatinine, Na, Urinary Cr, Urinary Na and FeNa%, there was highly statistically significant difference found between two groups regarding Urinary Na and Fe Na%, Platelets, AST, Bilirubin and Na, and there was no statistically significant difference found between two groups regarding HB, WBCs, ALT, Albumin, INR, Urea, Creatinine and Urinary Cr. While in the Correlation between NGAL With Age, HB, WBCs, Platelets, ALT, AST, Albumin, INR, Bilirubin, Urea, Creatinine, Na, Urinary Cr, Urinary Na and FeNa%, we found that there was Non statically significant correlation Between NGAL, Age, HB, WBCs, Platelets, ALT, Albumin, INR, Bilirubin, Urea, Creatinine, Na and Urinary Cr, and there was statically significant Negative correlation Between NGAL, Urinary Na and FeNa%, and there was statically significant positive correlation Between NGAL and AST. Conclusion It is well known that development of acute kidney injury (AKI) increases mortality in hospitalized cirrhotic patients; therefore many novel markers have been studied for early detection, differential diagnosis and prognosis in cirrhotic patients with AKI. NGAL is a newly identified member of the lipocalin family that is signifcantly expressed in injured epithelial cells. It can lead to rapid increases in NGAL secretion from glomeruli, thus increasing NGAL concentrations in the urine. In addition, its concentration often increases within 2 h of kidney injury. Urinary NGAL has the ability to differentiate between AKI types in patients with cirrhosis. This could improve risk stratification for patients admitted to the hospital with cirrhosis, perhaps leading to early ICU admission, transplant evaluation, and prompt initiation of HRS therapy and early management of AKI. These findings, if confirmed in larger cohorts, could lead to the development of biomarker algorithms to rapidly identify patients with HRS and ATN and accurately predict prognosis.

Point-of-care ultrasonography in cirrhosis-related acute kidney injury: How I do it

Discerning the etiology of acute kidney injury (AKI) in cirrhotic patients remains a formidable challenge due to diverse and overlapping causes. The conventional approach of empiric albumin administration for suspected volume depletion may inadvertently lead to fluid overload. In the recent past, point-of-care ultrasonography (POCUS) has emerged as a valuable adjunct to clinical assessment, offering advantages in terms of diagnostic accuracy, rapidity, cost-effectiveness, and patient satisfaction. This review provides insights into the strategic use of POCUS in evaluating cirrhotic patients with AKI. The review distinguishes basic and advanced POCUS, emphasizing a 5-point basic POCUS protocol for efficient assessment. This protocol includes evaluations of the kidneys and urinary bladder for obstructive nephropathy, lung ultrasound for detecting extravascular lung water, inferior vena cava (IVC) ultrasound for estimating right atrial pressure, internal jugular vein ultrasound as an alternative to IVC assessment, and focused cardiac ultrasound for assessing left ventricular (LV) systolic function and identifying potential causes of a plethoric IVC. Advanced POCUS delves into additional Doppler parameters, including stroke volume and cardiac output, LV filling pressures and venous congestion assessment to diagnose or prevent iatrogenic fluid overload. POCUS, when employed judiciously, enhances the diagnostic precision in evaluating AKI in cirrhotic patients, guiding appropriate therapeutic interventions, and minimizing the risk of fluid-related complications.

MicroRNA-599-Regulated Susceptibility to Acute Kidney Injury in Patients with Cirrhosis is Mediated by the Sirtuin 1 (SIRT1) rs4746720 Single Nucleotide Polymorphism.

The aim of this case-control study was to analyze the association between sirtuin 1 (SIRT1) single nucleotide polymorphism (SNP) and the risk of acute kidney injury (AKI) in Han Chinese patients with cirrhosis and to explore its potential mechanism. Twenty-nine AKI patients with cirrhosis (AKI group) and 87 non-AKI patients with cirrhosis (control group) were recruited from a Han Chinese population. SNaPshot sequencing technology was used for the detection of SNPs. Dual luciferase reporter vectors were constructed and co-transfected into HK-2 human proximal tubular epithelial cells. SIRT1-overexpressing recombinant plasmids were constructed and co-transfected into HK-2 cells. The expression of microRNA-599 (miR-599) and SIRT1/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α)/nuclear respiratory factor 1 (NRF1)/mitochondrial transcription factor A (TFAM) was detected by the quantitative polymerase chain reaction, and the expression of the corresponding proteins was detected by Western blotting. There were no statistically significant between-group differences in the genotype and allele frequencies of SIRT1 rs4746720. In the subgroup of patients with hepatic encephalopathy, the SIRT1 rs4746720 SNP was significantly associated with the development of AKI, and the risk of AKI in patients with the T allele was six times higher than in those with the C allele. The results of the in vitro experiments demonstrated that the T allele of SIRT1 rs4746720 increased the binding of miR-599 to the rs4746720 locus within the 3'-UTR of SIRT1 (p < 0.001). The results of the SIRT1-overexpressing recombinant plasmid experiments confirmed that the T allele of SIRT1 rs4746720 mediated the binding of miR-599, leading to decreased SIRT1 and PGC-1α, NRF1, and TFAM (p < 0.05). The SIRT1 rs4746720 SNP might be linked with AKI in cirrhotic patients, and the T allele increased the risk of AKI in those with hepatic encephalopathy. The rs4746720 SNP in the SIRT1 3'-UTR is linked to the development of AKI in cirrhotic patients with hepatic encephalopathy, potentially by mediating the binding of miR-599.

Prediction models combining zonulin, LPS, and LBP predict acute kidney injury and hepatorenal syndrome–acute kidney injury in cirrhotic patients

The development of acute kidney injury (AKI) and hepatorenal syndrome–acute kidney injury (HRS–AKI) in cirrhosis has been associated with intestinal barrier dysfunction and gut-kidney crosstalk. We use the related markers such as zonulin, lipopolysaccharides (LPS), and lipopolysaccharide-binding protein (LBP) to predict AKI and HRS–AKI in cirrhotic patients and evaluate their in vitro effects on intestinal (Caco-2) cells and renal tubular (HK-2) cells. From 2013 to 2020, we enrolled 70 cirrhotic patients and developed prediction models for AKI and HRS–AKI over a six-month period. There were 13 (18.6%) and 8 (11.4%) cirrhotic patients developed AKI and HRS–AKI. The prediction models incorporated zonulin, LPS, LBP, C-reactive protein, age, and history of hepatitis B for AKI, and zonulin, LPS, LBP, total bilirubin, and Child–Pugh score for HRS–AKI. The area under curve (AUC) for the prediction of AKI and HRS–AKI was 0.94 and 0.95, respectively. Furthermore, the conditioned medium of LPS+hrLBP pre-treated Caco-2 cells induced apoptosis, necrosis, and zonulin release in HK-2 cells, demonstrating the communication between them. This study found that zonulin, LPS, and LBP are potential practical markers for predicting AKI and HRS–AKI in cirrhotic patients, which may serve as potential targets for renal outcomes in cirrhotic patients.

Acute Kidney Injury in Liver Cirrhosis.

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.

Acute kidney injury in patients with acute-on-chronic liver failure: clinical significance and management.

Acute-on-chronic-liver failure (ACLF) refers to a phenomenon in which patients with chronic liver disease develop multiple organ failure due to acute exacerbation of underlying liver disease. More than 10 definitions of ACLF are extant around the world, and there is lack of consensus on whether extrahepatic organ failure is a main component or a consequence of ACLF. Asian and European consortiums have their own definitions of ACLF. The Asian Pacific Association for the Study of the Liver ACLF Research Consortium does not consider kidney failure as a diagnostic criterion for ACLF. Meanwhile, the European Association for the Study of the Liver Chronic Liver Failure and the North American Consortium for the Study of End-stage Liver Disease do consider kidney failure as an important factor in diagnosing and assessing the severity of ACLF. When kidney failure occurs in ACLF patients, treatment varies depending on the presence and stage of acute kidney injury (AKI). In general, the diagnosis of AKI in cirrhotic patients is based on the International Club of Ascites criteria: an increase of 0.3 mg/dL or more within 48 hours or a serum creatinine increase of 50% or more within one week. This study underscores the importance of kidney failure or AKI in patients with ACLF by reviewing its pathophysiology, prevention methods, and treatment approaches.

SERUM LIPOPOLYSACCHARIDE BINDING PROTEIN AS A PREDICTOR AND PROGNOSTIC BIOMARKER FOR CIRRHOSIS RELATED ACUTE KIDNEY INJURY

• Acute kidney injury (AKI), defined as an increase in serum creatinine ≥ 0.3 mg/dL (26.5 µmoL/L) ≤ 48 hours, or a 50% increase from baseline, is one of the most serious complications of liver cirrhosis. It occurs in about 19% of hospitalized cases with liver cirrhosis and it carries a bad prognosis. The acute kidney dysfunction is associated with mortality in cases with cirrhosis. Moreover, it usually occurs concomitantly with other cirrhosis related complications like spontaneous bacterial peritonitis (SBP) and bleeding varices.• Multiple factors could increase the risk for this complication including infections, hypovolemia, use of vasodilators, and non-steroidal anti-inflammatory drugs. Because of its unfavorable prognosis, potential triggers for AKI should be identified and removed in such cases. This includes correction of hypovolemia, discontinuation of nephrotoxic drugs, eradication of infections and management of other complications like variceal bleeding.• Lipopolysaccharide binding protein (LBP) is an acute phase protein that is synthesized by the liver. It is secreted into the blood stream in response to infection with Gram-negative bacteria. Recent studies have reported that LBP is an important mediator of AKI in critically ill patients. However, after intensive online research, the current literature had poor data regarding the role of that biomarker in AKI in cirrhotic patients.

Early echocardiographic signs of diastolic dysfunction predict acute kidney injury in cirrhotic patients.

Background:Cardiovascular dysfunction in cirrhotic patients affects survival and the development of cirrhotic complications. We aimed to evaluate potential echocardiographic parameters to predict mortality and acute kidney injury (AKI) in cirrhotic patients.Methods:A total of 103 cirrhotic patients who underwent echocardiography between February 2009 and August 2016 in Taipei Veterans General Hospital were retrospectively enrolled. Cardiac function was evaluated using transthoracic two-dimensional echocardiography with tissue Doppler imaging. Cox hazard regression analysis was used for assessing predictors for 1-year mortality and AKI within 1 year.Results:Baseline echocardiographic parameters were similar between survivors (n = 92) and nonsurvivors (n = 11). Lower serum levels of albumin, as well as higher albumin-bilirubin (ALBI) scores, Child-Pugh scores, and model for end-stage liver disease scores were observed in nonsurvivors. Cox proportional hazard regression analysis revealed Child-Pugh score as the only predictor of 1-year mortality. Baseline serum creatinine (Cr) > 1.5 mg/dL, total bilirubin > 2 mg/dL, and a higher E/e′ ratio predict occurrence of AKI within 1 year. Among patients with serum Cr < 1.5 mg/dL, an increased atrial filling velocity and higher ALBI scores predict AKI occurrence within 1 year.Conclusion:Severity of underlying liver disease but not echocardiographic parameters predicts 1-year mortality in cirrhosis. Early echocardiographic signs of diastolic dysfunction and higher ALBI scores may predict development of AKI in cirrhotic patients with serum Cr < 1.5 mg/dL.

Paracentesis-induced acute kidney injury in decompensated cirrhosis - prevalence and predictors.

Aim of the studyA subgroup of cirrhotic patients undergoing therapeutic paracentesis develop acute kidney injury (AKI) despite adequate colloidal replacement.The aim of the study was to determine the prevalence and predictors of paracentesis-induced AKI in cirrhotic patients with normal baseline renal parameters and adequate colloidal replacement.Material and methodsThis prospective, observational analytical study was undertaken between April 2015 and April 2017. All patients undergoing therapeutic paracentesis were enrolled as per inclusion and exclusion criteria. Based on Acute Kidney Injury Network (AKIN) criteria for AKI, comparative analysis was performed between those developing and not developing AKI for demography, renal parameters, frequency and quantity of paracentesis per session. Univariate and multivariate regression analyses were performed to determine the predictors of AKI.ResultsAltogether, 177 patients underwent 859 therapeutic paracenteses. Ninety-four paracentesis sessions resulted in an AKI (10.9%). The median number of paracenteses was 10 (range 1-25) and the median volume of fluid drained per paracentesis was 6 l (1-20 l). In univariate analysis, younger age (p < 0.02), higher MELD (Model For End-Stage Liver Disease) score (p < 0.0001), CTP (Child-Turcotte-Pugh) class C (p < 0.017) and prior history of renal dysfunction (p < 0.0001) were significantly associated with AKI. For each liter of fluid drained, the risk of AKI increased by 1.24 times. Frequency of paracentesis did not influence the AKI. In multivariate logistic regression, the significant predictors of AKI were past renal dysfunction, a higher MELD and volume of fluid tapped at paracentesis.ConclusionsPost-paracentesis AKI occurs in 10.9% of cases, despite adequate colloid replacement. For each 1 l of fluid drained during paracentesis, the risk of AKI increased by 1.24 times.

The clinical characteristics and risk factors for acute kidney injury in patients with cirrhosis

Objective: To investigate the clinical features and risk factors for acute kidney injury (AKI) in patients with cirrhosis. Methods: A total of 1 165 hospitalized patients with chronic liver diseases were enrolled. Among them, 94 patients had chronic hepatitis, while 1 071 patients were diagnosed as cirrhosis. The clinical data, renal and liver function were retrospectively analyzed. AKI was determined according to the criteria proposed by International Club of Ascites. Compared with chronic hepatitis group, the clinical features and risk factors for AKI in patients with cirrhosis were evaluated using logistic regression. Results: The prevalence of AKI in chronic hepatitis and cirrhosis were 4.26%(4/94) and 11.11% (119/1 071), respectively. The AKI rates in patients with liver function Child A, B and C were 3.77%(18/377), 10.88% (41/377) and 27.65%(60/217), respectively. The independent risk factors for AKI in cirrhotic patients included infections (OR=5.37, 95%CI 3.24-8.90, P=0.000), acute on chronic liver failure (ACLF, OR=4.55, 95%CI 2.60-7.98, P=0.000) and diabetes (OR=1.70, 95%CI 1.07-2.70, P=0.024). The mortality rate of cirrhotic patients with AKI was 36.97% within 2 months. Moreover, the mortality rates in stage Ⅰ, Ⅱ and Ⅲ AKI were 20.31%, 36.00% and 73.33%, respectively. Conclusions: The mortality rate of cirrhotic patients with stage Ⅲ AKI is extremely high. Infections, ACLF and diabetes are the independent risk factors for AKI in patients with cirrhosis.

Evaluation of Absolute Serum Creatinine Changes in Staging of Cirrhosis-Induced Acute Renal Injury and its Association with Long-term Outcomes

Background/Aims: To assess the prognostic accuracy of absolute serum creatinine (sCr) changes (‘Delta-sCr’) on the long-term outcomes in cirrhotic patients, and evaluate the performance of the ‘Delta-sCr’ approach to stage acute kidney injury (AKI), compared with the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Methods: We conducted a retrospective analysis of 333 hospitalized patients. We classified AKI stages using two methods: 1) KDIGO AKI criteria; 2) ‘Delta-sCr’ system, defined by the difference between the baseline and the peak sCr value during the hospitalization. The end point was the hazard of 1-year death. Results: The prevalence of AKI in cirrhotic patients was 18.01% by the KDIGO criteria, and 25.22% by the ‘Delta-sCr’ system. On multivariable Cox hazard analysis, both of the two methods were independent predictive factors of death (‘Delta-sCr’ system: OR=2.911, p<0.001), (KDIGO criteria: OR=2.065, p<0.001). However, the ‘Delta-sCr’ system provided a modest improvement in classification over the KDIGO criteria with a net reclassification improvement (NRI) of 28.7% (p<0.001) and integrated discrimination improvement (IDI) of 7.5% (p=0.03). And the predictive value of the ‘Delta-sCr’ system could be significantly improved (p=0.006), when combined with age and MELD score. Conclusion: The Delta-sCr is associated with the 1-year mortality. And the ‘Delta-sCr’ system may optimize the discrimination of risk prediction.

Acute kidney injury in patients with liver cirrhosis

Background Acute kidney injury (AKI) is a common complication of cirrhosis and confers a poor prognosis. There are many different causes for the development of AKI among patients with cirrhosis. Aim The aim was to study the incidence of AKI in cirrhotic patients and the different causes of AKI among them. Patients and methods Our study was conducted on 900 cirrhotic patients who were investigated in order to detect the incidence and causes of AKI. They were subjected to thorough history taking, complete clinical examination, investigations including: blood urea and serum creatinine, serum albumin, alanine aminotransferase, aspartate aminotransferase, bilirubin, prothrombin time and activity, international normalized ratio, complete blood count, total leukocytic count, C-reactive protein (CRP), hepatitis C virus antibodies, hepatitis B surface antigen, and pelvic-abdominal ultrasonography. Results AKI was found in 43.6% of the cirrhotic patients studied. The most predominant type was the prerenal AKI. Hepatorenal syndrome was found in 25.2% of patients. Septic causes included (spontaneous bacterial peritonitis in 24.2% of patients, chest infection in 22.6%, and urinary tract infection in 18.6%). Upper gastrointestinal bleeding was reported in 13% of cases. Postrenal causes were reported in 4.3% of cases, while intrinsic renal causes were found in 1% of cases. In 5.3% of cases, the cause of AKI was unidentified. We found that hemoglobin and serum albumin were significantly lower in patients with AKI compared with those without AKI. We found a significant positive correlation between serum creatinine and each of the following laboratory parameters: total leukocytic count, CRP, and international normalized ratio. On the other hand, we found a significant negative correlation between serum creatinine and hemoglobin and serum albumin. The CRP was the most independent risk factor in our patients. Conclusion AKI incidence in cirrhotic patients is significantly high. Prerenal AKI is the most predominant type. Sepsis was the most important prerenal causes of AKI in our cirrhotic patients. Anemia, hypoalbuminemia, hyperbilirubinemia, gastrointestinal bleeding, and sepsis increase the risk of AKI among cirrhotic patients.

Acute kidney injury in cirrhotic patients undergoing contrast-enhanced computed tomography.

Contrast medium administration is one of the leading causes of acute kidney injury (AKI) in different clinical settings. The aim of the study was to investigate occurrence and predisposing factors of AKI in cirrhotic patients undergoing contrast-enhanced computed tomography (CECT).Datasets of 1279 consecutively hospitalized cirrhotic patients were retrospectively analyzed. Two hundred forty-nine of 1279 patients (mean age 64 ± 11 years, 165 male) who had undergone CECT were selected on the basis of the availability of serum creatinine (sCr) values evaluated before and after CECT (CECT group). In analogy, 203/1279 cases (mean age 66 ± 10 years, 132 male) who had not undergone CECT and had been tested twice for sCr in 7 days were also included as controls (Control group). AKI network criteria were employed to assess contrast-induced AKI (CI-AKI) development. Apart from lack of narrowed double sCr measurements, additional exclusion criteria were active bacterial infections, nephrotoxic drugs intake, and estimated glomerular filtration rate <30 mL/min.AKI developed in 22/249 (8.8%) and in 6/203 (3%) of the CECT and the Control groups, respectively (P = 0.01). The multivariate logistic regression analysis showed that AKI was significantly associated with contrast medium administration (odds ratio [OR]: 3.242, 95% confidence interval [CI]: 1.255–8.375; P = 0.015), female sex (OR: 0.339, 95% CI: 0.139–0.827; P = 0.017), and sCr values (OR: 0.124, 95% CI: 0.016–0.975; P = 0.047). In the CECT group, presence of ascites (OR: 2.796, 95% CI: 1.109–7.052; P = 0.029), female sex (OR: 0.192, 95% CI: 0.073–0.510; P = 0.001), and hyperazotemia (OR: 1.018, 95% CI: 1.001–1.037; P = 0.043) correlated with CI-AKI development at multivariate analysis.CI-AKI is a quite frequent occurrence in cirrhotic patients with female sex, presence of ascites, and hyperazotemia being the predisposing factors.

Acute Kidney Injury in Cirrhotic Patients with Portal Hypertension

Acute kidney injury (AKI) is one of the most common manifestations encountered in clinical practice. It is associated with high morbidity and mortality in cirrhotic pre- and post-transplantation patients. Hepatorenal syndrome (HRS), a special form of AKI in cirrhotic patients, was recognized as a consequence of renal vasoconstriction from systemic/renal hemodynamic alterations developed in advanced cirrhosis with portal hypertension. Recently, multiple factors-such as infection/inflammation, underlying glomerulonephritis, bile cast, or increased abdominal pressure-have been considered to contribute to renal dysfunction in cirrhotic patients, which were presumed to induce HRS. Moreover, in addition to changing the definition of AKI in the nephrologic guidelines, the new AKI definition for early diagnosis and intervention based on characteristics of liver cirrhosis has been proposed in an international meeting. This article provides a comprehensive and recent review of AKI definition, laying out the topics in accordance with the pathophysiologic mechanisms and therapeutic interventions of AKI in cirrhotic patients with portal hypertension.

Renal dysfunction in cirrhosis.

Renal dysfunction causes significant morbidity in cirrhotic patients. Diagnosis is challenging because it is based on serum creatinine, which is used to calculate estimated glomerular filtration rate, which itself is not an ideal measure of renal function in patients with cirrhosis. Finding the exact cause of renal injury in patients with cirrhosis remains problematic due to the limitations of the current diagnostic tests. The purpose of this review is to highlight studies used to diagnose renal dysfunction in patients with renal dysfunction and review current treatments. New diagnostic criteria and classification of renal dysfunction, especially for acute kidney injury (AKI), have been proposed in hopes of optimizing treatment and improving outcomes. New biomarkers that help to differentiate structural from functional AKI in cirrhotic patients have been developed, but require further investigation. Vasoconstrictors are the most commonly recommended treatment of hepatorenal syndrome (HRS). Given the high mortality in patients with type 1 HRS, all patients with HRS should be evaluated for liver transplantation. When renal dysfunction is considered irreversible, combined liver-kidney transplantation is advised. Development of new biomarkers to differentiate the different types of AKI in cirrhosis holds promise. Early intervention in cirrhotic patients with renal dysfunction offers the best hope of improving outcomes.

Acute kidney injury in patients with chronic liver disease

Acute kidney injury (AKI) is a frequent clinical event in patients with liver disease, compounding their prognosis. Furthermore, it is likely that the occurrence of AKI has a detrimental impact on the subsequent renal function and the long-term survival of these patients. Recently, some authors advocated the use of new diagnostic criteria for detecting acute kidney injury in patients with cirrhosis. These criteria are based on the rapidity and extent of the creatinine increase comparing to the basal creatinine and also on the kinetics of diuresis decrease. Although their validity in this population requires further studies to be clearly established, these new criteria could have two advantages: (1) to allow earlier diagnosis of AKI and, thus, hepatorenal syndrome for which earlier intervention could improve patients' survival; and (2) to promote more intensive monitoring of renal function in these patients with high risk of AKI. Finally, recent practice guidelines about the prevention and treatment of general AKI have been published which should be useful in optimising the management of AKI in cirrhotic patients.

Hepatorenal Syndrome: A Critical Update

Acute kidney injury (AKI) is common in cirrhotic patients with ascites. Although not the primary etiology of AKI in cirrhotic patients, hepatorenal syndrome (HRS) is a unique form of AKI that develops only in cirrhotic patients. Intense renal vasoconstriction is the hallmark of HRS. Different mechanisms contribute to renal vasoconstriction, with splanchnic vasodilatation and reduced effective blood volume playing a central role. Diagnostic criteria for HRS have been developed and were recently modified, but diagnosing HRS and differentiating it from other causes of AKI in cirrhotic patients continues to be a difficult task in some patients. Given its overall dismal prognosis, strategies to prevent HRS have been developed and proved to be effective in reducing HRS prevalence among cirrhotic patients. Liver transplantation is the ultimate treatment, but more than one treatment modality can be utilized as a bridge to transplantation. This review provides an update on our current understanding of HRS with emphasis on the underlying pathophysiological mechanisms involved, difficulties in diagnosis, and different treatment modalities.

Acute kidney injury as a causal factor in mortality associated with hepatorenal syndrome

We examine how acute kidney injury (AKI) contributes to mortality in patients with liver failure. Hepatorenal syndrome (HRS) is a form of AKI in cirrhotic patients, which is defined as a purely physiologic derangement in renal function without any effect on renal parenchyma. Recent literature challenges this understanding. Little attention is paid to the presence of renal pathology and inflammatory alterations that occur as a result of HRS and their contribution to morbidity and mortality. In this paper, we propose that any type of AKI in the presence of liver disease is an inflammatory condition. The combination of AKI and liver failure produces a "toxic milieu" of cytokines, chemokines, and nitric oxide pathway metabolites that directly cause endothelial dysfunction affecting multiple organ systems. These global effects contribute to the increased short- and long-term mortality which has been established in the epidemiologic literature.