ArticleHepatology (Baltimore, Md.)2018
Disruption of Renal Arginine Metabolism Promotes Kidney Injury in Hepatorenal Syndrome in Mice.
Article in Hepatology (Baltimore, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- Arginase 2 deficiency mitigates sepsis-associated acute kidney injury by alleviating lipid accumulation.Clinical and translational medicine · 2026Article
- The Role of Nitric Oxide in Chronic Liver Disease: A Review.Journal of clinical and translational hepatology · 2026Review
- Hepatokine fibrinogen-like protein 1 drives liver-kidney crosstalk to promote renal fibrosis.Nature communications · 2026Article
- The Link between Alcohol Consumption and Kidney Injury.The American journal of pathology · 2026Review
- Selective Depletion of Gut Gram-Negative Bacteria Attenuates Alcohol Binge-Induced Cardiovascular Dysfunction by Lowering Cardiac Anandamide Levels.The American journal of pathology · 2026Article
- Development and validation of machine learning models for predicting acute kidney injury in acute-on-chronic liver failure: a multimodel comparative study.Renal failure · 2025Article
- Immunomodulatory Functions of Intercalated Cells in Kidney Autoimmunity.bioRxiv : the preprint server for biology · 2025Article
- Multiplatform Metabolomic Profiling of the Unilateral Ureteral Obstruction Murine Model of CKD.International journal of molecular sciences · 2025Article
- CCL2 supports human hepatocytes long-term expansion for bioartificial liver therapy to relieve acute liver failure and extrahepatic complications.International journal of biological sciences · 2025Article
- Safety evaluation of irinotecan: a real-world disproportionality analysis using FAERS and JADER databases during the time period 2004-2024.Frontiers in pharmacology · 2025Article
- Effects of Transjugular Intrahepatic Portosystemic Shunt on Renal and Pulmonary Function in Hepatic Decompensation with and without Hepatorenal and Hepatopulmonary Syndromes: A Review.Journal of clinical and translational hepatology · 2024Review
- Hypoxia-inducible factor-1α attenuates renal podocyte injury in male rats in a simulated high-altitude environment by upregulating Krüppel-like factor 4 expression.Experimental physiology · 2024Article
- Hepatorenal Syndrome-Novel Insights into Diagnostics and Treatment.International journal of molecular sciences · 2023Review
- Cirrhotic Cardiomyopathy Following Bile Duct Ligation in Rats-A Matter of Time?International journal of molecular sciences · 2023Article
- Impact of renal tubularFrontiers in molecular biosciences · 2023Article
- The progress to establish optimal animal models for the study of acute-on-chronic liver failure.Frontiers in medicine · 2023Review
- Fucoidan alleviates the hepatorenal syndrome through inhibition organic solute transporter α/β to reduce bile acids reabsorption.Current research in pharmacology and drug discovery · 2023Article
- Article
- Organ Crosstalk in Acute Kidney Injury: Evidence and Mechanisms.Journal of clinical medicine · 2022Review
- A mouse model of hepatic encephalopathy: bile duct ligation induces brain ammonia overload, glial cell activation and neuroinflammation.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Tubular dysfunction is an important feature of renal injury in hepatorenal syndrome (HRS) in patients with end-stage liver disease. The pathogenesis of kidney injury in HRS is elusive, and there are no clinically relevant rodent models of HRS. We investigated the renal consequences of bile duct ligation (BDL)-induced hepatic and renal injury in mice in vivo by using biochemical assays, real-time polymerase chain reaction (PCR), Western blot, mass spectrometry, histology, and electron microscopy. BDL resulted in time-dependent hepatic injury and hyperammonemia which were paralleled by tubular dilation and tubulointerstitial nephritis with marked upregulation of lipocalin-2, kidney injury molecule 1 (KIM-1) and osteopontin. Renal injury was associated with dramatically impaired microvascular flow and decreased endothelial nitric oxide synthase (eNOS) activity. Gene expression analyses signified proximal tubular epithelial injury, tissue hypoxia, inflammation, and activation of the fibrotic gene program. Marked changes in renal arginine metabolism (upregulation of arginase-2 and downregulation of argininosuccinate synthase 1), resulted in decreased circulating arginine levels. Arginase-2 knockout mice were partially protected from BDL-induced renal injury and had less impairment in microvascular function. In human-cultured proximal tubular epithelial cells hyperammonemia per se induced upregulation of arginase-2 and markers of tubular cell injury.
conclusionWe propose that hyperammonemia may contribute to impaired renal arginine metabolism, leading to decreased eNOS activity, impaired microcirculation, tubular cell death, tubulointerstitial nephritis and fibrosis. Genetic deletion of arginase-2 partially restores microcirculation and thereby alleviates tubular injury. We also demonstrate that BDL in mice is an excellent, clinically relevant model to study the renal consequences of HRS. (Hepatology 2018; 00:000-000).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.