Disruption of Renal Arginine Metabolism Promotes Kidney Injury in Hepatorenal Syndrome in Mice

Varga, Zoltán V.; Erdélyi, Katalin; Pálóczi, János; Çınar, Reşat; Zsengellér, Zsuzsanna K.; Jourdan, Tony; Mátyás, Csaba; Németh, Balázs Tamás; Guillot, Adrien; Xiang, Xiaogang; Mehal, Adam; Haskó, György; Stillman, Isaac E.; Rosen, Seymour; Gao, Bin; Kunos, George; Pacher, Pál

doi:10.1002/hep.29915

Cited by 44 publications

(21 citation statements)

References 47 publications

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“…Elevated ammonia in cirrhosis disrupts metabolism of arginine, an essential amino acid for the synthesis of nitric oxide. 27 Decreased availability of nitric oxide in the renal microcirculation contributes to impaired renal blood flow and consequent functional and ischemic kidney injury.…”

Section: Circulatory Dysfunctionmentioning

confidence: 99%

Hepatorenal syndrome: pathophysiology, diagnosis, and management

Simonetto

Ginès

Kamath

2020

BMJ

151

133

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Hepatorenal syndrome (HRS), the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduction in renal blood flow and glomerular filtration rate. Hepatorenal syndrome is diagnosed when kidney function is reduced but evidence of intrinsic kidney disease, such as hematuria, proteinuria, or abnormal kidney ultrasonography, is absent. Unlike other causes of acute kidney injury (AKI), hepatorenal syndrome results from functional changes in the renal circulation and is potentially reversible with liver transplantation or vasoconstrictor drugs. Two forms of hepatorenal syndrome are recognized depending on the acuity and progression of kidney injury. The first represents an acute impairment of kidney function, HRS-AKI, whereas the second represents a more chronic kidney dysfunction, HRS-CKD (chronic kidney disease). In this review, we provide critical insight into the definition, pathophysiology, diagnosis, and management of hepatorenal syndrome.

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Section: Circulatory Dysfunctionmentioning

confidence: 99%

Hepatorenal syndrome: pathophysiology, diagnosis, and management

Simonetto

Ginès

Kamath

2020

BMJ

151

133

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“…This alteration is concomitant with a loss of fenestrations in peritubular endothelial cells and increases in the ammonia levels, as also seen in NAFLD. Besides, there is renal vascular inflammation, which contributes to renal dysfunction [ 106 ]. Proinflammatory cytokines upregulate the NOX4 expression in endothelial cells and NOS uncoupling, which results in elevated O 2 · − production.…”

Section: Influence Of Oxidative Stress In Nonalcoholic Fatty Livermentioning

confidence: 99%

“…These effects could be correlated with the NAFLD-induced proinflammatory state [ 113 ]. Moreover, the renal parenchymal impairment mediated by ischemia due to NAFLD-induced ED is the primary mechanism involved in tubular cell death and interstitial fibrosis in the kidney [ 96 , 106 ].…”

Section: Influence Of Oxidative Stress In Nonalcoholic Fatty Livermentioning

confidence: 99%

Role of Oxidative Stress in Hepatic and Extrahepatic Dysfunctions during Nonalcoholic Fatty Liver Disease (NAFLD)

González

Huerta-Salgado

Orozco-Aguilar

et al. 2020

Oxidative Medicine and Cellular Longevity

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Nonalcoholic fatty liver disease (NAFLD) is a pathology that contains a broad liver dysfunctions spectrum. These alterations span from noninflammatory isolated steatosis until nonalcoholic steatohepatitis (NASH), a more aggressive form of the disease characterized by steatosis, inflammatory status, and varying liver degrees fibrosis. NAFLD is the most prevalent chronic liver disease worldwide. The causes of NAFLD are diverse and include genetic and environmental factors. The presence of NASH is strongly associated with cirrhosis development and hepatocellular carcinoma, two conditions that require liver transplantation. The liver alterations during NAFLD are well described. Interestingly, this pathological condition also affects other critical tissues and organs, such as skeletal muscle and even the cardiovascular, renal, and nervous systems. Oxidative stress (OS) is a harmful state present in several chronic diseases, such as NAFLD. The purpose of this review is to describe hepatic and extrahepatic dysfunctions in NAFLD. We will also review the influence of OS on the physiopathological events that affect the critical function of the liver and peripheral tissues.

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“…In the present work, the induction of liver injury was confirmed by an increase in the serum levels of conventional hepatic biomarkers such as AST, ALT, γGT, and AP, assayed biochemically. Changes in uric acid and urea levels were also found, indicating initial renal consequences [ 3 , 22 , 23 ]. Conventional serum biochemistry also confirmed the increase in bilirubin, in particular the conjugated form, very much in keeping with the literature for both animal models and human extrahepatic cholestasis [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…BDL in rodents is a model of extrahepatic biliary obstruction, used to investigate both liver injury and associated extrahepatic disease, such as cholemic nephropathy or encephalopathy [ 3 , 4 , 5 , 6 , 7 ]. BDL induces a cascade of an ensuing, dynamic series of acute and chronic injuries [ 5 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Serum and Hepatic Autofluorescence as a Real-Time Diagnostic Tool for Early Cholestasis Assessment

Croce

Bottiroli

Pasqua

et al. 2018

IJMS

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While it is well established that various factors can impair the production and flow of bile and lead to cholestatic disease in hepatic and extrahepatic sites, an enhanced assessment of the biomarkers of the underlying pathophysiological mechanisms is still needed to improve early diagnosis and therapeutic strategies. Hence, we investigated fluorescing endogenous biomolecules as possible intrinsic biomarkers of molecular and cellular changes in cholestasis. Spectroscopic autofluorescence (AF) analysis was performed using a fiber optic probe (366 nm excitation), under living conditions and in serum, on the livers of male Wistar rats submitted to bile duct ligation (BDL, 24, 48, and 72 h). Biomarkers of liver injury were assayed biochemically. In the serum, AF analysis distinctly detected increased bilirubin at 24 h BDL. A continuous, significant increase in red-fluorescing porphyrin derivatives indicated the subversion of heme metabolism, consistent with an almost twofold increase in the serum iron at 72 h BDL. In the liver, changes in the AF of NAD(P)H and flavins, as well as lipopigments, indicated the impairment of mitochondrial functionality, oxidative stress, and the accumulation of oxidative products. A serum/hepatic AF profile can be thus proposed as a supportive diagnostic tool for the in situ, real-time study of bio-metabolic alterations in bile duct ligation (BDL) in experimental hepatology, with the potential to eventually translate to clinical diagnosis.

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Disruption of Renal Arginine Metabolism Promotes Kidney Injury in Hepatorenal Syndrome in Mice

Cited by 44 publications

References 47 publications

Hepatorenal syndrome: pathophysiology, diagnosis, and management

Hepatorenal syndrome: pathophysiology, diagnosis, and management

Role of Oxidative Stress in Hepatic and Extrahepatic Dysfunctions during Nonalcoholic Fatty Liver Disease (NAFLD)

Serum and Hepatic Autofluorescence as a Real-Time Diagnostic Tool for Early Cholestasis Assessment

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