In clinical medicine, hyponatremia is highly prevalent and frequently misdiagnosed, leading to substantial mismanagement and iatrogenic morbidity. Its differential diagnosis includes numerous diseases with diverse etiologies, making accurate assessment challenging. Despite extensive literature and guidelines on hyponatremia, most patients do not receive adequate evaluation due to the limitations of diagnostic algorithms, which rely on low-value clinical signs and are unable to identify concurrent conditions. In this review, we examine the range of laboratory tests available for hyponatremia assessment. Understanding renal mechanisms of solute and water exchange (e.g., fractional excretion) is essential for selecting appropriate tests and interpreting their diagnostic value. Additionally, detailed electrolyte and acid-base assessments remain critical for establishing a definitive diagnosis. We comprehensively discuss the selection of laboratory tests for specific differential diagnoses of hyponatremia. Importantly, in cases of acute hyponatremia, rapid correction should take precedence over a complete diagnostic workup. Ultimately, a thorough understanding of laboratory evaluation is crucial for accurately diagnosing hyponatremia. This paper critically reviews the available literature and explores relevant diseases in the context of associated laboratory parameters.

To investigate the association between early blood pressure drop and worsening renal function (WRF) in ICU patients with liver failure and to evaluate their clinical outcomes.

Retrospective observational study.

Intensive Care Medicine.

Patients admitted to the ICU for the first time during their first hospitalization; diagnosed with liver failure according to the International Classification of Diseases, Ninth and Tenth Revision codes; and aged ≥18 years were included. Patients with a peak systolic blood pressure (SBP) drop of <0 mmHg were excluded.

We analyzed data of ICU patients with liver failure from the Medical Information Mart for Intensive Care IV version 2.2 database. Descriptive statistics, analysis of variance, Kruskal-Wallis test, and chi-square test were employed for analysis. Multivariate linear regression models were used to assess the determinants of blood pressure decline. Cox proportional hazards and generalized additive models were used to evaluate MAIN VARIABLES OF INTEREST: The relationship between blood pressure decline, WRF, and 60-day in-hospital mortality were evaluated, along with subgroup analyses.

Peak SBP drop was independently associated with higher risks of WRF (P < 0.001) and 60-day in-hospital mortality (P < 0.001), even after adjusting for potential confounders, including baseline SBP. The independent risk relationship observed between peak diastolic blood pressure, mean arterial pressure drop, and the occurrence of WRF and 60-day in-hospital mortality was similar.

In ICU patients with liver failure, a significant early drop in blood pressure was associated with a higher incidence of WRF, increased risk of 60-day in-hospital mortality, and poorer prognoses.

Over the past several years, there has been a wealth of new data pertaining to the management of complications of cirrhosis, resulting in several important updates to best practices and consensus guidelines. Despite these advancements and numerous recent targeted quality initiatives, hospitalizations resulting from complications of cirrhosis remain frequent, costly and associated with poor patient outcomes. An emphasis on evidence-based management of hospitalized patients with decompensated cirrhosis has the potential to decrease readmission rates and length of stay while improving overall patient outcomes. Herein, we provide an updated, evidence-based overview of the optimal inpatient management of the most frequently encountered complications associated with cirrhosis.

The 2021 Chronic Kidney Disease Epidemiology Collaboration equation [CKD-EPI 2021] is a race-neutral equation recently developed and rapidly implemented as a reference standard to estimate glomerular filtration rate(GFR). However, its role in cirrhosis has not been examined especially in low GFR. We analyzed the performance of CKD-EPI 2021 compared to other equations with protocol-measured GFR (mGFR) in cirrhosis. We analyzed 2090 unique adult patients with cirrhosis undergoing protocol GFR measurements using iothalamate clearance from 1985 to 2015 when listed for liver transplantation at Baylor University in Dallas and Fort Worth, Texas. Using mGFR as a reference standard, the CKD-EPI 2021 was compared to CKD-EPI 2012, Modification of Diet in Renal Disease-4, Modification of Diet in Renal Disease-6, Royal Free Hospital, and GFR Assessment in Liver disease overall and in certain subgroups (ascites, mGFR ≤ 30 mL/min/1.73 m 2 , diagnosis, Model for End-Stage Liver Disease and gender). We examined bias (difference between eGFR and mGFR), accuracy (p30: eGFR within ± 30% of mGFR) and agreement between eGFR and mGFR categories. CKD-EPI 2021 had the second lowest bias across the entire range of GFR after GFR Assessment in Liver disease (6.6 vs. 4.6 mL/min/1.73 m 2 , respectively, p < 0.001). The accuracy of CKD-EPI 2021 was similar to CKD-EPI 2012 (p30 = 67.8% vs. 67.9%, respectively) which was higher than the other equations ( p < 0.001). It had a similar performance in patients with ascites, by diagnoses, Model for End-Stage Liver Disease subgroups, by gender, and in non-Black patients. However, it had a relatively higher overestimation in mGFR ≤ 30 mL/min/1.73 m 2 than most equations (18.5 mL/min/1.73m 2 , p < 0.001). Specifically, 64% of patients with mGFR ≤ 30 mL/min/1.73m 2 were incorrectly classified as a less severe CKD stage by CKD-EPI 2021. In Blacks, CKD-EPI 2021 underestimated eGFR by 17.9 mL/min/1.73 m 2 , which was higher than the alternate equations except for Royal Free Hospital ( p < 0.001). The novel race-neutral eGFR equation, CKD-EPI 2021, improves the GFR estimation overall but may not accurately capture true kidney function in cirrhosis, specifically at low GFR. There is an urgent need for a race-neutral equation in liver disease reflecting the complexity of kidney function physiology unique to cirrhosis, given implications for organ allocation and dual organ transplant.

Acute kidney injury (AKI) represents a commonly seen condition in the natural course of cirrhosis associated with unfavourable outcomes.

To evaluate and compare the pooled mortality rates of patients with cirrhosis, with versus without AKI, across different clinical settings and diagnostic criteria.

A systematic search of several databases was performed up to Oct 2023. Meta-analysis was performed using a generalised linear mixed model with a random effects model for all calculations.

A total of 59 studies comparing patients with cirrhosis, with and without AKI, were included in the meta-analysis, encompassing 1,153,193 individuals with AKI and 4,630,814 without AKI. AKI development predisposed to significantly higher short (in-hospital and 30-days)-, intermediate (90-days)- and long (1-year)-term mortality rates in both inpatients and outpatients. Remarkably, patients with AKI admitted to intensive care unit (ICU) or diagnosed with acute-on-chronic liver failure (ACLF) experienced the higher short-term mortality rates, reaching 76% [95% confidence interval (CI): 73%-79%] and 54% (95%CI: 33%-73%), respectively. AKI staging correlated with mortality risk, with higher stages indicating higher mortality rates, while the timing of AKI development, whether community-acquired or hospital-acquired, plays a crucial role in patient prognosis, with distinct mortality patterns observed in each group. The selection of diagnostic criteria for AKI may also impact its association with the short-term mortality risk.

AKI substantially affects the prognosis of patients with cirrhosis, especially those in ICU and/or with ACLF. Prognosis is also greatly influenced by the AKI stage, timing of onset and diagnostic criteria.

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.

Renal dysfunction is prevalent in advanced chronic liver disease (aCLD) and is associated to liver-related death (LRD). This makes a reliable evaluation of renal function (RF) a crucial aspect. RF can be estimated by formulas or measured by gold standard method. Estimated RF is not reliable in aCLD. However, there is a lack of information on the reliability of formulas in the prediction of LRD.

We analysed a cohort of patients with aCLD in whom RF was measured by the plasma clearance of iohexol (mGFR) and estimated (eGFR) by formulas: MDRD, CKD-EPI, Royal Free Hospital (RFHC), GRAIL and Mindikoglu-eGFR. LRD was defined as death from hepatic causes. Multivariable analysis was used to evaluate association of mGFR or eGFR with LRD.

161 patients were evaluated, with median follow-up of 28 months, 58 died from LRD. In overall group mGFR (OR 0.99; p = 0.022) and formulas: CKD-EPI (OR 0.98; p = 0.044), GRAIL (OR 0.98; p = 0.038) was associated with LRD. In patients with normal creatinine levels (≤ 1.1 mg/dL), mGFR (OR 0.99; p = 0.031) was whereas any formula was not associated with LRD.

eGFR appears as an unreliable method for predicting LRDs in aCLD, especially in those with lower creatinine levels. By contrast, mGFR seems to be a superior predictor.

Aging is a complex process manifesting at molecular, cellular, organ, and organismal levels. It leads to functional decline, disease, and ultimately death, but the relationship between these fundamental biomedical features remains elusive. By applying elastic net regularization to plasma proteome data of over 50,000 human subjects in the UK Biobank and other cohorts, we report interpretable organ-specific and conventional aging models trained on chronological age, mortality, and longitudinal proteome data. These models predict organ/system-specific disease and indicate that men age faster than women in most organs. Accelerated organ aging leads to diseases in these organs, and specific diets, lifestyles, professions, and medications influence organ aging rates. We then identify proteins driving these associations with organ-specific aging. Our analyses reveal that age-related chronic diseases epitomize accelerated organ- and system-specific aging, modifiable through environmental factors, advocating for both universal whole-organism and personalized organ/system-specific anti-aging interventions.

Hepatorenal syndrome-acute kidney injury (HRS-AKI) occurs in the setting of advanced chronic liver disease, portal hypertension, and ascites. HRS-AKI is found in ∼20% of patients presenting to the hospital with AKI, but it may coexist with other causes of AKI and/or with preexisting chronic kidney disease, thereby making the diagnosis challenging. Novel biomarkers such as urinary neutrophil gelatinase-associated lipocalin may be useful. While HRS-AKI is a functional form of AKI related to circulatory and neurohormonal dysfunction, there is increasing recognition of the importance of systemic inflammation and the renal microenvironment. Early diagnosis and initiation of HRS-AKI-specific treatment can improve outcomes. The mainstay of therapy is a vasoconstrictor (terlipressin or norepinephrine) combined with albumin, which achieves resolution of HRS in 40-50% of cases. Liver transplantation is the only option for patients failing to respond to medical therapies.

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.

Chronic alcohol exposure is common in all societies and is seen at high rates during coronial (medicolegal) postmortem examinations. In both setting of acute alcohol intoxication and chronic misuse, a wide range of pathologies and mechanisms of death may be encountered, particularly with regard to sudden, unexpected or violent deaths. These warrant special attention. In this review, we examine the approach to postmortem examination where alcohol is likely to have played a key role in death. Attention is given to the scene of death, patterns of traumatic injury, systemic pathology (particularly of chronic alcohol exposure), seizures related to alcohol, and appropriate biochemical investigations.

Cirrhosis is a known risk factor for morbidity and mortality following surgical procedures and has been associated with increased complications, hospital length of stay (LOS), and cost of admission following total joint arthroplasty. However, a paucity of literature exists evaluating the effect of cirrhosis on postoperative outcomes following total shoulder arthroplasty (TSA). The purpose of this study is to evaluate the short-term outcomes following elective primary TSA in patients with cirrhosis compared to matched controls.

The Nationwide Readmissions Database was queried from 2016 to 2020 to identify patients who underwent elective primary TSA. Patients with a diagnosis of cirrhosis (n = 627) were matched in a 1:1 proportion to patients who did not have cirrhosis. Bivariate statistical analyses were performed to compare preoperative demographic and comorbidity data, postoperative outcomes, and hospital utilization metrics between the two groups. Following Bonferroni correction, an alpha value of 0.003 defined significance.

Patients with cirrhosis exhibited higher rates of postoperative medical and implant-related complications following primary TSA, including acute renal failure (6.3% vs 1.1%: p < 0.001), urinary tract infection (3.5% vs 0.6%; p < 0.001), transfusions (3.0% vs 0.2%; p < 0.001), acute respiratory distress syndrome (2.9% vs 0.2%: p = 0.002), surgical site infection (2.0% vs 0.2%: p = 0.001), dislocation (2.1% vs 0.0%: p < 0.001), and prosthetic loosening (1.5% vs 0.0%; p = 0.002). These patients also exhibited higher rates of all-cause complications (32% vs 9.2%: p < 0.001) and mortality (1.5% vs 0.0%; p = 0.002) within 180 days of surgery and had an increased cost of admission ($24,633 vs $18,500; p < 0.001) and LOS (2.6 vs 1.5 days; p < 0.001).

Patients with cirrhosis were found to have increased risk of medical and surgical complications, higher costs, and longer LOS following TSA. These findings can assist orthopedic surgeons in developing strategies in the preoperative period to mitigate complications in this at-risk patient group.

Level III - Retrospective cohort study.

In various disease contexts, magnesium abnormalities are associated with acute kidney injury (AKI) incidence. However, this association remains unclear and has not been systematically investigated in patients with cirrhosis. Hence, we aimed to elucidate the association between admission serum magnesium levels and AKI incidence in intensive care unit (ICU)-admitted cirrhotic patients.

A retrospective cohort study was conducted using MIMIC-IV2.2 data, focusing on critically ill patients with cirrhosis. We employed univariable and multivariable logistic regression and restricted cubic spline analyses to robustly address our research objectives. To further substantiate the findings, subgroup and sensitivity analyses were also conducted.

Among the 3,228 enrolled ICU-admitted cirrhotic patients, 34.4% were female, and the overall AKI incidence was 68.6% (2,213/3,228). Multivariable logistic regression analysis revealed an independent relationship between elevated serum magnesium levels and increased AKI risk (OR = 1.55 [95% CI = 1.15-2.09], p = 0.004). Compared with individuals with serum magnesium levels < 1.6 mg/dL, individuals with serum magnesium levels in Q2 (1.6-2.6 mg/dL) and Q3 (≥2.6 mg/dL) had adjusted ORs for AKI of 1.89 (95% CI = 1.34-2.65, p < 0.001) and 2.19 (95% CI = 1.27-3.75, p = 0.005), respectively. The restricted cubic spline analysis revealed that AKI risk increased linearly with increasing serum magnesium levels. Subgroup analysis revealed that the association between serum magnesium levels and AKI incidence was remarkably stable in subgroup analysis (all Pinteraction >0.05).

High serum magnesium concentrations were significantly associated with an increased AKI risk in ICU-admitted patients with cirrhosis. Further randomized trials are needed to confirm this association.

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.

Intravenous albumin reduces mortality in spontaneous bacterial peritonitis (SBP). We sought to characterize albumin use for SBP over time and investigate patient-level and hospital-level factors associated with use.

A retrospective cohort study in the Veterans Health Administration between 2008 and 2021 evaluated trends and patient-level, practice-level, and facility-level factors associated with use among patients with cirrhosis hospitalized for SBP confirmed with ascitic fluid criteria.

Among 3,871 veterans with SBP, 803 (20.7%) did not receive albumin, 1,119 (28.9%) received albumin but not per guidelines, and 1,949 (50.3%) received albumin per guidelines; use increased from 66% in 2008 to 88% in 2022. Veterans who identified as Black compared with White were less likely to receive guideline-recommended albumin (Odds ratio [OR] 0.76, 95% confidence interval [CI] 0.59-0.98) in all analyses. Guideline-recommended albumin was more likely to be administered to veterans with Child-Turcotte-Pugh class B (OR 1.39, 95% CI 1.17-1.64) and C (OR 2.21, 95% CI 1.61-3.04) compared with Child-Turcotte-Pugh A; and acute kidney injury Stage 1 (OR 1.48, 95% CI 1.22-1.79), Stage 2 (OR 2.17, 95% CI 1.62-2.91), and Stage 3 (OR 1.68, 95% CI 1.18-2.40) compared with no acute kidney injury. gastroenterology/hepatology consultation (OR 1.60, 95% CI 1.29-1.99), nephrology consultation (OR 1.60, 95% CI 1.23-2.07), and having both gastroenterology/hepatology and nephrology consultations (OR 2.17, 95% CI 1.60-2.96) were associated with higher albumin administration. In exploratory analyses accounting for interactions between model for end-stage liver disease sodium and albumin, guideline-recommended albumin was associated with lower in-hospital mortality (HR 0.90, 95% CI 0.85-0.96).

Future studies should investigate optimizing albumin use for SBP to reduce the variability and mitigate healthcare disparities.

Patients with liver cirrhosis are prone to develop severe bacterial infections. Pharmacokinetics (PK) of antibiotics in cirrhosis are potentially affected by impaired biotransformation phases 0-3 and consequences of portal hypertension such as portovenous shunting, ascites formation and/or acute kidney injury (AKI). We aimed to elucidate to what extent PK of selected antibiotics and, therefore, dosage recommendations are affected in adults with cirrhosis.

We performed a systematic search in PubMed, Embase, Cochrane and CINAHL on effects of cirrhosis on PK profiles of ceftriaxone, fosfomycin, gentamicin, meropenem, nitrofurantoin, piperacillin/tazobactam and vancomycin in adults. Antibiotics were selected based on the lack of specific dosing recommendations for adults with cirrhosis. We included studies reporting on ≥1 of the following PK parameters: AUC, half-life (t½), CL, volume of distribution (Vd), peak (Cmax) or trough concentrations (Cmin).

We identified 15 studies (ceftriaxone, n = 5; gentamicin, n = 3; meropenem n = 5; vancomycin, n = 2), including 379 patients with cirrhosis, of which two were of high quality. No eligible studies were identified for fosfomycin, nitrofurantoin or piperacillin/tazobactam. Ceftriaxone unbound concentration increased in cirrhosis, but was mitigated by increased renal CL. Gentamicin levels in ascitic fluid were comparable to those in plasma. Meropenem PK parameters were not altered in cirrhosis without AKI, but in the presence of AKI a decrease in CL was observed. In contrast, vancomycin CL decreased in advanced cirrhosis.

Available data in studies of mostly moderate quality suggest that PK of ceftriaxone, meropenem and vancomycin are altered in cirrhosis. More advanced PK studies are needed to provide specific dosing recommendations.

Despite liver transplantation (LT) is considered the optimal treatment for hepatocellular carcinoma (HCC), particularly in patients with impaired liver function, the shortage of donors has forced the application of very restrictive criteria for selecting ideal candidates for whom LT can offer the best outcome. With the evolving LT landscape due to the advent of direct-acting antivirals (DAAs) and the steady increase in donors, major efforts have been made to expand the transplant eligibility criteria for HCC. In addition, the emergence of immune checkpoint inhibitors (ICIs) for the treatment of HCC, with demonstrated efficacy in earlier stages, has revolutionized the therapeutic approach for these patients, and their integration in the setting of LT is challenging. Management of immunological compromise from ICIs, including the wash-out period before LT and post-LT immunosuppression adjustments, is crucial to balance the risk of graft rejection against HCC recurrence. Additionally, the effects of increased immunosuppression on non-hepatic complications must be understood to prevent them from becoming obstacles to long-term OS.

In this review, we will evaluate the emerging evidence and its implications for the future of LT in HCC. Addressing these novel challenges and opportunities, while integrating the current clinical evidence with predictive algorithms, would ensure a fair balance between individual patient needs and the overall population benefit in the LT system.

How to cite this article: Kothekar AT, Shah KB. Echoes and Shadows: Predicting Hepatorenal Syndrome Outcomes with Lung Ultrasound and X-rays. Indian J Crit Care Med 2024;28(11):993-994.

Renal dysfunction is a common complication of cirrhosis, occurring either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. To date, no study has comprehensively assessed multiple renal function parameters in hospitalized patients with cirrhosis through a multiparametric analysis of renal biochemistry markers.

We conducted a retrospective, observational study including all consecutive patients hospitalized with cirrhosis who underwent a 43-multiparametric renal function assessment between January 1, 2021, and June 30, 2023.

All patients showed at least one of the following renal abnormalities: Kidney Disease: Improving Global Outcomes stage G2 or higher, sodium and/or chloride excretion fraction <1%, electrolyte-free water clearance <0.4 mL/min, or tubular maximum phosphate reabsorption capacity <0.8 mmol/L. The estimated glomerular filtration rate equations significantly overestimated the measured creatinine clearance with median differences of +14 mL/min/1.73 m2 (95% CI 6-29) and +9 mL/min/1.73 m2 (95% CI 2-15) for European Kidney Function Consortium equations, respectively. Notably, 54% and 39% of patients demonstrated estimated glomerular filtration rates exceeding 30% of the measured creatinine clearance when the Chronic Kidney Disease - Epidemiology Collaboration and European Kidney Function Consortium formulas were employed, respectively. Substantial discrepancies in Kidney Disease: Improving Global Outcomes stage assignments were observed between the estimated glomerular filtration rate- and measured creatinine clearance-based assessments.

This study underscores the value of a multiparametric renal function assessment as a routine tool for evaluating renal function in patients with cirrhosis. A high prevalence of medically actionable renal abnormalities spanning multiple renal function modules, including alterations in glomerular function, salt and solute-free water excretion, and proximal tubule phosphate reabsorption, has been demonstrated in hospitalized patients with cirrhosis.

Serum creatinine (Scr) may be not suited to timely and accurately reflect kidney injury related to chronic liver disease. Currently, the ability of arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) sequences to evaluate renal blood flow (RBF) and blood oxygen in chronic liver disease remains to be verified.

To investigate the value of ASL and BOLD imaging in evaluating hemodynamics and oxygenation changes during kidney injury in an animal model of chronic liver disease.

Prospective.

Chronic liver disease model was established by subcutaneous injection of carbon tetrachloride. Forty-three male Sprague-Dawley rats (8 weeks) were divided into a pathological group (0, 2, 4, 6, 8, 12 weeks, each group: N = 6) and a continuous-scanning group (N = 7).

3-T, ASL, BOLD, and T2W.

Regions of interest in the cortex (CO), outer stripe of the outer medulla (OSOM), and inner stripe of the outer medulla (ISOM) are manually delineated. The RBF and T2* values at each time point (0, 2, 4, 6, 8, 12 weeks) are measured and compared. Hematoxylin-eosin score (HE Score, damage area scoring method), alpha-smooth muscle actin (α-SMA), hypoxia-inducible factor-1alpha (HIF-1α), peritubular capillar (PTC) density, Scr, and neutrophil gelatinase-associated lipocalin were harvested.

Analysis of variance, Spearman correlation analysis, Kruskal-Wallis tests, and receiver operating characteristic analysis with the area under the curve (AUC). A P-value <0.05 was considered statistically significant.

Renal RBF and T2* values of CO, OSOM, and ISOM were significantly different from baseline. Both RBF and T2* were significantly correlated with HE Score, α-SMA, HIF-1α, and PTC density (|r| = 0.406-0.853). RBF demonstrated superior diagnostic capability in identifying severe kidney injury in this model of chronic liver disease (AUC = 0.964).

Imaging by ASL and BOLD may detect renal hemodynamics and oxygenation changes related to chronic liver disease early.

5 TECHNICAL EFFICACY: Stage 2.

The objective of this study is to develop and validate an effective prognostic nomogram for predicting the short-term survival rate of patients with acute heart failure (AHF) complicated by acute kidney injury (AKI) who are admitted to the intensive care unit (ICU).

We conducted an analysis of data from patients of AHF with AKI spanning the period from 2008 to 2019, utilizing the MIMIC-IV database. Patients were randomly divided into training and validation sets. The training set employed the least absolute shrinkage and selection operator regression model to identify predictors of AKI. Subsequently, a dynamic nomogram was constructed using multivariate Cox regression analysis within the training set and was subsequently validated using the validation set. The nomogram's predictive accuracy, calibration, and clinical utility were evaluated through the concordance index (C-index), calibration plots, and decision curve analysis (DCA).

A total of 978 AHF patients with AKI were analyzed. Multivariate analysis identified serum creatinine, race, age, use of human albumin, use of vasoactive drug, and hemoglobin as independent predictors significantly influencing the short-term prognosis of AHF patients with AKI upon ICU admission. The C-index for the training and validation sets were 0.81 (95%CI: 0.74-0.87) and 0.80 (95 % CI: 0.67-0.92), respectively. The calibration plot of the nomogram demonstrated a close alignment between predicted and observed probabilities. Furthermore, the DCA confirmed the clinical utility of the nomogram.

This study presents a dynamic nomogram that incorporates clinical risk factors and can be conveniently utilized to predict short-term prognosis for AHF patients with AKI upon ICU admission.

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.

Kidney injury is a significant complication in end-stage liver disease (ESLD), leading to increased morbidity and mortality. While liver transplant alone (LTA) can promote kidney recovery (KR), non-recovery associates with adverse outcomes, but the underlying pathophysiology is still unclear. We studied 10 LTA recipients with or without kidney failure (KF) and measured serum levels of OPN and TIMP-1 (previously identified predictors of KR), 92 proinflammatory proteins (Olink), and urinary cell populations. Our findings revealed elevated OPN and TIMP-1 levels in KF patients, strongly correlated with tubular epithelial cells in urine. Proteomic analysis showed distinct profiles in KF, non-KF, and healthy donors, indicating an ongoing proinflammatory signature in KF. Cytokines correlated with OPN and TIMP-1 levels. We propose that high pre-LTA OPN and TIMP-1 levels are crucial for tubular regeneration and normalize with kidney recovery. Insufficient pre-LTA OPN levels may lead to persistent kidney failure. Our present data also newly indicate that kidney failure post-LTA is an active condition, in which tubular cells are persistently shed in the urine. The strict association between systemic inflammation and tubular cell loss suggests a pathogenic link that could offer therapeutic opportunities to promote kidney recovery.

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.

Background/Objectives: Liver transplantation (LT) is typically performed as a surgery to treat end-stage liver disease (ESLD). Factors influencing acute kidney injury (AKI) post-living-donor LT (LDLT) have been identified; however, the potential role of the D-dimer-to-fibrinogen ratio (DFR) in predicting AKI remains unexplored. Therefore, we analyzed the relationship between DFR levels and the occurrence of AKI following LT. Methods: We retrospectively analyzed 648 recipients after 76 were excluded based on the exclusion criteria. Multivariate logistic regression and propensity score (PS) matching analyses were performed to evaluate the association between a high DFR (>1.05) and AKI. Results: After LDLT, AKI was observed in 148 patients (22.8%). A high DFR (>1.05) was independently associated with AKI. Multivariate logistic regression analysis showed that patients with a DFR above this threshold were four times more susceptible to AKI than those with a low DFR. A high DFR was also significantly associated with AKI in the propensity score-matched patients. Conclusions: Our findings suggest that incorporating preoperative DFR assessment into the management of patients undergoing LDLT could enhance the risk stratification for postoperative AKI.

The management of acute kidney injury (AKI) in cirrhosis is challenging. The EASL guidelines proposed an algorithm for the management of AKI, but this has never been validated. We aimed to prospectively evaluate this algorithm in clinical practice.

We performed a prospective cohort study in consecutive hospitalized patients with cirrhosis and AKI. The EASL management algorithm includes identification/treatment of precipitating factors, 2-day albumin infusion in patients with AKI ≥stage 1B, and treatment with terlipressin in patients with hepatorenal syndrome (HRS-AKI). The primary outcome was treatment response, which included both full and partial response. Secondary outcomes were survival and adverse events associated with terlipressin therapy.

A total of 202 AKI episodes in 139 patients were included. Overall treatment response was 80%, while renal replacement therapy was required in only 8%. Response to albumin infusion was achieved in one-third of episodes. Of patients not responding to albumin, most (74%) did not meet the diagnostic criteria of HRS-AKI, with acute tubular necrosis (ATN) being the most common phenotype. The response rate in patients not meeting the criteria for HRS-AKI was 70%. Only 30 patients met the diagnostic criteria for HRS-AKI, and their response rate to terlipressin was 61%. Median time from AKI diagnosis to terlipressin initiation was only 2.5 days. While uNGAL (urinary neutrophil gelatinase-associated lipocalin) could differentiate ATN from other phenotypes (AUROC 0.78), it did not predict response to therapy in HRS-AKI. Ninety-day transplant-free survival was negatively associated with MELD-Na, ATN and HRS-AKI as well as uNGAL. Three patients treated with terlipressin developed pulmonary edema.

The application of the EASL AKI algorithm is associated with very good response rates and does not significantly delay initiation of terlipressin therapy.

The occurrence of acute kidney injury (AKI) in patients with cirrhosis is associated with poor short-term mortality. Improving its rapid identification and prompt management was the focus of the recently proposed EASL AKI algorithm. This is the first prospective study demonstrating that high AKI response rates are achieved with the use of this algorithm, which includes identification of AKI, treatment of precipitating factors, a 2-day albumin challenge in patients with AKI ≥1B, and supportive therapy in patients with persistent AKI not meeting HRS-AKI criteria or terlipressin with albumin in those with HRS-AKI. These findings support the use of this algorithm in clinical practice.

Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions.

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.

To evaluate the predictive value of blood coagulation and routine blood indices for rebleeding after endoscopic treatment of ruptured esophagogastric fundal varices (EGVB) in cirrhotic patients with hepatitis B infection.

This retrospective analysis included 248 patients with hepatitis B-related cirrhosis and EGVB who received initial endoscopic treatment from October 2019 to March 2022 and were followed up for 12 months. Patients were divided into rebleeding and non-rebleeding groups. Laboratory indices were analyzed, and univariate and multivariate analyses identified predictors of rebleeding. The efficacy of a logistic regression model was evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA), and a risk factor nomogram was constructed for assessing the predictive efficiency of those risk factors.

Univariate analysis showed significant differences in portal vein diameters and lower Child-Pugh scores in the rebleeding group in contrast to those in the non-rebleeding group. Key laboratory markers such as platelet count (PLT), albumin (ALB), alanine aminotransferase (ALT), lymphocytes (LYM), and prognostic nutritional index (PNI) were lower, while prothrombin time (PT) and lactate levels (LN) were higher in the rebleeding group than those in the non-rebleeding group. Multivariate analysis identified portal vein diameter, PLT, ALT, PT, LYM, and PNI as significant predictors of rebleeding. The logistic model demonstrated high accuracy (AUC=0.986) and clinical value, validated by ROC curves, calibration curves (C-index =0.986), and DCA results. A risk factor predictive nomogram was successfully constructed.

This study developed a logistic regression model with a nomogram for predicting EGVB-related rebleeding in patients with hepatitis B-related cirrhosis, achieving an AUC of 0.986, indicating high accuracy and significant clinical relevance.

Ferroptosis is a form of non-apoptotic regulated cell death (RCD) that depends on iron and is characterized by the accumulation of lipid peroxides to lethal levels. Ferroptosis involves multiple pathways including redox balance, iron regulation, mitochondrial function, and amino acid, lipid, and glycometabolism. Furthermore, various disease-related signaling pathways also play a role in regulating the process of iron oxidation. In recent years, with the emergence of the concept of ferroptosis and the in-depth study of its mechanisms, ferroptosis is closely associated with various biological conditions related to kidney diseases, including kidney organ development, aging, immunity, and cancer. This article reviews the development of the concept of ferroptosis, the mechanisms of ferroptosis (including GSH-GPX4, FSP1-CoQ1, DHODH-CoQ10, GCH1-BH4, and MBOAT1/2 pathways), and the latest research progress on its involvement in kidney diseases. It summarizes research on ferroptosis in kidney diseases within the frameworks of metabolism, reactive oxygen biology, and iron biology. The article introduces key regulatory factors and mechanisms of ferroptosis in kidney diseases, as well as important concepts and major open questions in ferroptosis and related natural compounds. It is hoped that in future research, further breakthroughs can be made in understanding the regulation mechanism of ferroptosis and utilizing ferroptosis to promote treatments for kidney diseases, such as acute kidney injury(AKI), chronic kidney disease (CKD), diabetic nephropathy(DN), and renal cell carcinoma. This paves the way for a new approach to research, prevent, and treat clinical kidney diseases.

Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.

Acute kidney injury (AKI) is a commonly seen condition in the natural course of cirrhosis. The aim of this study was to evaluate the pooled incidence and risk factors of AKI in different clinical stages and situations in patients with cirrhosis.

Search was conducted on 13 December 2023 across MEDLINE (PubMed), Embase, and Cochrane databases. Meta-analysis was performed using a generalized linear mixed model.

In total, 73 studies with 5,202,232 patients were finally enrolled in the meta-analysis. AKI commonly occurs among hospitalized cirrhotics experiencing any decompensation event (29%) as well as among stable outpatients (28%) throughout a 1-year follow-up period. On admission, patients with infection or sepsis/septic shock had the highest AKI rate (47%), followed by those with hepatic encephalopathy (41%). Furthermore, the severity of liver disease proved to be a substantial driver for AKI development, while patients at intensive care unit had the greatest AKI incidence (61%).

Both hospitalized patients and stable outpatients with cirrhosis exhibited an elevated susceptibility to AKI. Patients at intensive care unit and those with severe liver disease, infection, sepsis/septic shock, hepatic encephalopathy, or acute on chronic liver failure upon admission are at higher risk for AKI.