Search Results (46)

Acute kidney injury (AKI) is a serious clinical condition that is linked to markedly higher rates of morbidity and mortality in cirrhosis patients. Its diagnosis is challenging due to overlapping clinical and laboratory features among causes such as hepatorenal syndrome (HRS), acute tubular injury (ATI), and prerenal hypovolemia. In order to address the distinct pathophysiology and clinical context of cirrhosis, the definitions and classification of AKI have changed over time, moving from RIFLE and AKIN to KDIGO and ICA-AKI. Because cirrhosis patients have altered muscle mass and fluid retention, traditional markers like serum creatinine (sCr) and urine output have significant limitations. Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and cystatin C (CysC) are some of the new biomarkers that have shown promise in early AKI detection and in differentiating structural from functional kidney injury. NGAL and KIM-1 are sensitive indicators of tubular damage with potential prognostic implications. IL-18 reflects inflammatory injury, and CysC offers a more reliable measure of glomerular filtration. Incorporating these markers may improve early diagnosis, risk stratification, and treatment decisions, representing a key direction for future research in managing AKI in cirrhosis. Full article

Hepato-renal crosstalk is a complex biological communication between liver and kidneys mediated by various factors, including cellular, endocrine, and paracrine molecules. This interaction highlights the functional consequences that damage in one organ can have on the other. In particular, the liver and kidney play a pivotal role in maintaining body homeostasis, as they are both involved in the excretion of toxic bioproducts and drugs. The overlap of liver and kidney disease has both therapeutic and prognostic implications. Therefore, a better understanding of the mechanisms involved in the pathogenesis of this bidirectional crosstalk is essential for improving the management of these clinical conditions and patient outcomes. Specifically, a multidisciplinary approach involving hepatologists and nephrologists is crucial to reduce the long-term burden of these clinical settings. This review focuses on the hepato-renal crosstalk in the context of liver and kidney disease, with particular attention to acute kidney injury associated with liver injury, hepatorenal syndrome and, chronic kidney disease in the context of liver fibrosis. Full article

Ralstonia eutropha H16, a metabolically versatile bacterium, has gained prominence as a microbial platform for sustainable bioproduction. While its capabilities in synthesizing single-cell proteins and biodegradable materials are well documented, comprehensive strain-level safety evaluations remain insufficient for food-grade applications. This study systematically assessed the safety of R. eutropha H16 through genomic, phenotypic, and toxicological analyzes. Genomic analyzes revealed the absence or minimal presence of virulence factors and antibiotic resistance genes, aligning with microbiological safety standards. Phenotypic investigations demonstrated a limited gastric fluid tolerance (pH 2.5, survival rate 25.70% after 3 h) and intestinal fluid persistence (pH 8, 44.67% viability after 3 h), coupled with an exceptional bile salt tolerance (0.2% w/v). Antioxidant assays confirmed the fermentation broth specifically scavenges DPPH free radicals (14.60 ± 1.24 μg Trolox/mL), whereas bacterial suspensions and cell-free supernatants exhibited a strong hydroxyl radical scavenging (>90 U/mL) and superoxide anion inhibition (>100 U/L). Acute toxicity testing indicated no mortality or histopathological abnormalities, with an LD₅₀ value exceeding 1 × 10¹¹ CFU/kg. Subacute toxicity studies (28-day, 1 × 10⁸–1 × 10¹⁰ CFU/kg) revealed no significant effects on growth, hematology, or organ function. Minor alterations in serum biochemistry might be attributed to physiological adaptation. Subacute exposure induced transient serum ALT fluctuations without hepatorenal dysfunction, while maintaining hematological parameters within physiological ranges. Collectively, these results substantiate the safety of R. eutropha H16 for food-related applications while underscoring the necessity of strain-specific risk assessments for industrial microbial platforms. Full article

The liver and kidneys are two of the most vital organs, each with distinct but overlapping functions essential for maintaining homeostasis. The complex interplay between these organs, commonly referred to as liver-kidney crosstalk, plays a crucial role in the pathophysiology of several acute and chronic conditions in childhood. Despite its importance, the precise biological mechanisms driving this interaction remain incompletely understood. This crosstalk is particularly significant in various pediatric diseases (e.g., Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), Hepatorenal Syndrome (HRS), genetic and metabolic disorders, etc.) where shared pathophysiological factors—including systemic inflammation, metabolic disturbances, oxidative stress, and vascular dysfunction—simultaneously affect both organs. Clinically, this interaction presents unique challenges in diagnosing, managing, and treating liver-kidney diseases in affected children. Understanding the pathogenic mechanisms underlying liver-kidney crosstalk is essential for improving patient care and outcomes through an integrated, multidisciplinary approach and personalized treatment strategies. This review aims to explore liver-kidney crosstalk in key pediatric diseases, offering a comprehensive overview of current knowledge, clinical challenges, and potential therapeutic interventions in this complex field. Full article

Sepsis, defined as a dysregulated host response to infection, is one of the leading causes of mortality worldwide. It unleashes in the organism a cascade of molecules, cytokines, and proteins which leads to an inflammatory storm. If this response to infection is uncontrolled, any organ is susceptible to damage. Acute kidney injury (AKI) is one of the most frequent organ dysfunctions in septic patients, and while it can be reversible, its presence leads to a higher burden of morbidity and mortality. While serum creatinine is essential in evaluating kidney function, the pathophysiology of AKI is not completely elucidated, and a plethora of novel biomarkers have been studied in the hope of an early diagnosis and fast treatment. While the liver is not as affected by sepsis, it plays an important role as a guardian by providing acute-phase proteins, activating neutrophils, and controlling iron balance. Acute liver failure (ALF) could impair the organism’s capacity to contain and eliminate pathogens. Some molecules have been associated with either AKI or ALF, although biomarkers specific for organ dysfunction are difficult to validate. The aim of this review is to understand the role of several molecules in the pathophysiology of sepsis and their clinical ability for diagnosing or predicting sepsis-induced hepato-renal dysfunction. Full article

Coking activities produce high concentrations of aromatic compounds (ACs) and related substances, which may have impacts on human health. However, the health effects of these substances on humans exposed to coking sites have not been fully elucidated. A total of 637 people were recruited to participate in this cross-sectional study. Using multiple linear regression and Bayesian kernel machine regression, we investigated the relationships between the urinary parent or metabolite forms of ACs (including metabolites of PAHs and their derivatives, nitrophenols, and chlorophenols) and hepatorenal biomarkers (HRBs), including total bilirubin, aspartate aminotransferase/alanine aminotransferase, serum uric acid, creatinine, albumin/globulin, and urea. The HRBs adopted in this study can effectively represent the status of human liver and kidney function. Mediation analysis was performed to investigate the possible mediating relationship between ACs and HRBs using oxidative stress markers as mediators. Our study indicated that ACs were significantly associated with increases in TBIL, AST/ALT, A/G, and UA, as well as a significant decrease in Cr. UREA showed no association with ACs among coking workers. The oxidative stress markers 8-hydroxy-2’-deoxyguanosine, 8-iso-prostaglandin-F2α, and 8-iso,15(R)-prostaglandinF2α mediated the induction of ACs on TBIL. Our results suggest that AC exposure in coking workers may be associated with adverse changes in hepatorenal biomarkers. This study highlights the significant impact of ACs from coking activities on workers’ hepatorenal biomarkers, providing crucial evidence for health risk assessment and prevention in affected populations. Full article

Several studies have explored the effects of single or binary mixtures of sweeteners on both healthy individuals and those with diabetes. However, there is limited research on the impact of a combination of four sweeteners supplemented with dietary minerals. Steviol glycosides, extracted from Stevia rebaudiana, offer a zero-calorie sweetness that exerts minimal influence on blood glucose levels. When combined with other sweeteners, they can reduce the required quantity of each component thus mitigating the potential side effects. Furthermore, the incorporation of chromium picolinate into sweeteners may enhance insulin sensitivity and glucose metabolism and diminish insulin resistance in both diabetic and non-diabetic individuals. This study aimed to evaluate the effects of commercial mixed sweeteners (acesulfame-K, sucralose, sorbitol, and steviol glycoside) supplemented with chromium picolinate (MSSC) on diabetes-related markers and complications in healthy and type 2 diabetic rats (T2D). Over six weeks, diabetic rats received daily oral administration of MSSC at a standard dosage. The results demonstrated that MSSC significantly reduced weight loss in diabetic rats, lowered fasting blood glucose levels, enhanced hexokinase activity, and improved pancreatic antioxidative capacities. Additionally, MSSC treatment led to notable reductions in serum triglycerides, cholesterol, malondialdehyde (MDA), and LDL cholesterol levels. The treatment also modulated specific renal function parameters, and moderately reversed the necrotic architectures of the liver and pancreatic β cells. These results indicate that long-term administration of MSSC may alleviate certain diabetic complications without adverse effects on non-diabetic individuals. Further clinical studies are strongly recommended to evaluate the safety and efficacy of MSSC in diverse populations. Full article

Background and objectives: Liver cirrhosis is a chronic, progressive condition characterized by fibrosis and architectural distortion of the liver, leading to impaired liver function and severe complications. Accurately predicting these complications is crucial to the improvement of patient outcomes. Therefore, this study aimed to evaluate the accuracy of various non-invasive biomarkers and clinical scores in assessing the risk of complications among cirrhotic patients. Materials and methods: We conducted an observational retrospective study involving 236 cirrhotic patients from two tertiary care hospitals in Italy and Romania, in a timespan ranging from January 2021 to March 2024. Data on clinical characteristics, liver function tests, hematological indices, various non-invasive biomarkers, and clinical scores were collected and analyzed. Receiver operating characteristic analysis was performed to assess the accuracy of these biomarkers and clinical scores in predicting complications, including the presence of varices and hepato-renal syndrome. Results: The Child–Pugh score showed the highest accuracy for cirrhosis-related complications, with an area under curve (AUC) = 0.667. The red cell distribution width coefficient of variation followed closely with an AUC = 0.646. While the Child–Pugh score had a high specificity (85.42%), its sensitivity was low (37.97%). In patients with varices, non-invasive scores such as platelet distribution width (PDW) and the RDW-to-platelet ratio (RPR) showed modest predictive ability, with an AUC = 0.594. For hepato-renal syndrome, the Model for End-Stage Liver Disease (MELD) score showed the highest diagnostic accuracy with an AUC = 0.758. Conclusions: The most reliable biomarkers for detecting complications, varices, and hepato-renal syndrome, are, respectively, the Child–Pugh Score, PDW along with RPR, and the MELD score. However, while these scores remain valuable, the moderate diagnostic accuracy of other indices suggests the need for a more integrated approach to risk stratification. Future research should focus on validating these tools across different populations and incorporating emerging biomarkers to enhance predictive accuracy and inform more effective clinical decision-making. Full article

The liver and kidneys are crucial for glucose homeostasis and are seriously damaged in diabetes. Cocoa and carob possess antidiabetic activity, but their hepatorenal protective effects, especially when combined with antidiabetic drugs, are unknown. The aim of this study is to investigate the effects of a cocoa–carob-supplemented diet (CC), either alone or in combination with metformin, on liver and kidney damage in Zucker diabetic fatty (ZDF) rats, a type 2 diabetes model. Male ZDF animals received a control or CC-supplemented diet, with or without metformin, and Zucker lean rats were fed the control diet. The CC-supplemented diet improved glucose tolerance and insulin resistance and alleviated functional and structural alterations in the diabetic liver and renal cortex. The CC-supplemented diet also ameliorated oxidative stress, downregulated apoptosis, and improved insulin signalling and glucose homeostasis. The combination of CC and metformin boosted several benefits as certain parameters related to morphological and structural alterations, apoptosis, oxidative stress, glucose homeostasis, and insulin resistance, were improved in comparison to animals receiving the CC-supplemented diet or metformin alone; these include the following: apoptotic index, Bax, hepatic insulin receptor or glutathione content, among others. These results demonstrate that the CC-supplemented diet alleviates the hepatorenal damage in type 2 diabetic ZDF rats, highlighting its potential alone or as an adjuvant therapy. Full article

Background: Colorectal cancer (CRC) patients experience multiple types of chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine chemotoxicity’s prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: −1.44) and GI toxicity (β:1.85) (p-values < 0.01). Older adults (>65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (p-values < 0.05). Conclusions. Our findings highlight the importance of closely monitoring and managing chemotoxicity in CRC patients receiving chemotherapy. Full article

Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM significantly contributes to mortality and morbidity in patients who undergo liver transplantation and contributes to the pathogenesis of hepatorenal syndrome/acute kidney injury. There is currently no specific treatment. The traditional management for non-cirrhotic cardiomyopathies, such as vasodilators or diuretics, is not applicable because an important feature of cirrhosis is decreased systemic vascular resistance; therefore, vasodilators further worsen the peripheral vasodilatation and hypotension. Long-term diuretic use may cause electrolyte imbalances and potentially renal injury. The heart of the cirrhotic patient is insensitive to cardiac glycosides. Therefore, these types of medications are not useful in patients with CCM. Exploring the therapeutic strategies of CCM is of the utmost importance. The present review summarizes the possible treatment of CCM. We detail the current status of non-selective beta-blockers (NSBBs) in the management of cirrhotic patients and discuss the controversies surrounding NSBBs in clinical practice. Other possible therapeutic agents include drugs with antioxidant, anti-inflammatory, and anti-apoptotic functions; such effects may have potential clinical application. These drugs currently are mainly based on animal studies and include statins, taurine, spermidine, galectin inhibitors, albumin, and direct antioxidants. We conclude with speculations on the future research directions in CCM treatment. Full article

Portal hypertension (PH) is a complex clinical challenge with severe complications, including variceal bleeding, ascites, hepatic encephalopathy, and hepatorenal syndrome. The gut microbiota (GM) and its interconnectedness with human health have emerged as a captivating field of research. This review explores the intricate connections between the gut and the liver, aiming to elucidate how alterations in GM, intestinal barrier function, and gut-derived molecules impact the development and progression of PH. A systematic literature search, following PRISMA guidelines, identified 12 original articles that suggest a relationship between GM, the gut–liver axis, and PH. Mechanisms such as dysbiosis, bacterial translocation, altered microbial structure, and inflammation appear to orchestrate this relationship. One notable study highlights the pivotal role of the farnesoid X receptor axis in regulating the interplay between the gut and liver and proposes it as a promising therapeutic target. Fecal transplantation experiments further emphasize the pathogenic significance of the GM in modulating liver maladies, including PH. Recent advancements in metagenomics and metabolomics have expanded our understanding of the GM’s role in human ailments. The review suggests that addressing the unmet need of identifying gut–liver axis-related metabolic and molecular pathways holds potential for elucidating pathogenesis and directing novel therapeutic interventions. Full article

Exposure to mercuric chloride (HgCl₂), either accidental or occupational, induces substantial liver and kidney damage. Coenzyme Q10 (CoQ10) is a natural antioxidant that also has anti-inflammatory and anti-apoptotic activities. Herein, our study aimed to investigate the possible protective effects of CoQ10 alone or loaded with albumin nanoparticles (CoQ10NPs) against HgCl₂-induced hepatorenal toxicity in rats. Experimental animals received CoQ10 (10 mg/kg/oral) or CoQ10NPs (10 mg/kg/oral) and were injected intraperitoneally with HgCl₂ (5 mg/kg; three times/week) for two weeks. The results indicated that CoQ10NP pretreatment caused a significant decrease in serum liver and kidney function markers. Moreover, lowered MDA and NO levels were associated with an increase in antioxidant enzyme activities (SOD, GPx, GR, and CAT), along with higher GSH contents, in both the liver and kidneys of intoxicated rats treated with CoQ10NPs. Moreover, HgCl₂-intoxicated rats that received CoQ10NPs revealed a significant reduction in the hepatorenal levels of TNF-α, IL-1β, NF-κB, and TGF-β, as well as an increase in the hepatic level of the fibrotic marker (α-SMA). Notably, CoQ10NPs counteracted hepatorenal apoptosis by diminishing the levels of Bax and caspase-3 and boosting the level of Bcl-2. The hepatic and renal histopathological findings supported the abovementioned changes. In conclusion, these data suggest that CoQ10, alone or loaded with albumin nanoparticles, has great power in reversing the hepatic and renal tissue impairment induced by HgCl₂ via the modulation of hepatorenal oxidative damage, inflammation, and apoptosis. Therefore, this study provides a valuable therapeutic agent (CoQ10NPs) for preventing and treating several HgCl₂-induced hepatorenal disorders. Full article

Hepatorenal syndrome stands as one of several potential triggers of acute kidney injury in individuals grappling with either acute or persistent liver ailments. The nature of the decline in kidney function has led to the identification of two variants of hepatorenal syndrome. In cases where terlipressin therapy is accessible, the initial approach involves administering terlipressin alongside albumin. Terlipressin, a synthetic analog of vasopressin, boasts double the preference for vasopressin V1 receptors compared to V2 receptors. The FDA granted approval to terlipressin in September 2022, demonstrating its intrinsic activity, although a significant portion of its function arises from its transformation into lysine vasopressin. This article provides a comprehensive examination of terlipressin’s various pharmacodynamic and pharmacokinetic facets, as well as its clinical utility, aiming to keep the scientific community well informed about its safe and efficient utilization. Full article

Cajanus cajan (L.) Millsp., also known as pigeon pea, has roots that have exhibited much pharmacological potential. The present study was conducted to assess the safe dose of the ethanolic extract of C. cajan roots (EECR95) and to analyze the main soy isoflavones contents. In vitro, we investigated the mutagenicity and cytotoxic effect of EECR95 on Salmonella typhimurium-TA98 and TA100 (by Ames tests) and RAW 264.7, L-929, and HGF-1 cell lines (by MTT tests) for 24 h of incubation. We found no mutagenic or cytotoxic effects of EECR95. After administration of 0.2 or 1.0 g/kg bw of EECR95 to both male and female Wistar rats for 90 days, there were no significant adverse effects on the behaviors (body weight, water intake, and food intake), organ/tissue weights, or immunohistochemical staining, and the urine and hematological examinations of the rats were within normal ranges. EECR95 potentially decreases renal function markers in serum (serum uric acid, BUN, CRE, and GLU) or liver function markers (cholesterol, triglyceride, and glutamic-pyruvate-transaminase (GPT)). We also found that EECR95 contained five soy isoflavones (genistein, biochanin A, daidzein, genistin, and cajanol), which may be related to its hepatorenal protection. Based on the high dose (1.0 g/kg bw) of EECR95, a safe daily intake of EECR95 for human adults is estimated to be 972 mg/60 kg person/day. Full article