Increased renal expression and urinary excretion of <scp>TLR</scp>4 in acute kidney injury associated with cirrhosis

Shah, Naina; Mohamed, F.; Jover-Cobos, M; Macnaughtan, Jane; Davies, Nathan; Moreau, Richard; Paradis, Valérie; Moore, Kevin; Mookerjee, Rajeshwar P.; Jalan, Rajiv

doi:10.1111/liv.12047

Cited by 114 publications

(78 citation statements)

References 33 publications

(51 reference statements)

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“…Renal dysfunction in patients with cirrhosis with superimposed inflammation was reported previously to be associated with significant tubular injury (Shah et al, 2013). This model also showed elevated oxidative stress in the present study, represented by the increased MDA and the reduced total antioxidant which might be a biomarker of tissue destruction and inflammation in both kidney and liver.…”

Section: Discussionsupporting

confidence: 65%

Evaluation of the therapeutic effect of <em>Nigella sativa</em> crude oil and its blend with omega-3 fatty acid-rich oils in a modified hepatorenal syndrome model in rats

et al. 2015

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SUMMARY:In the present study, the hepato and reno-protective effect of Nigella sativa crude oil and its binary blend with omega-3 fatty acid-rich oils (fish and flaxseed oils) was studied in a modified hepatorenal syndrome model (MHRS) in rats. MHRS was induced through feeding a high fructose diet followed by an intraperitoneal injection of galactosamine hydrochloride. Nigella oil and its different blends were given as a daily oral dose to MHRS rats. Two control groups of MHRS and normal healthy rats were run. Different biochemical and nutritional parameters were assessed. The induction of MHRS produced liver and kidney dysfunction, and elevated oxidative stress, an inflammatory biomarker, endothelin 1, and plasma cholesterol. Reduced plasma high density lipoprotein cholesterol, albumin and Ca and elevated urinary N-acetyl-β-D-Glucosaminidase and liver fats were noticed. The administration of Nigella crude oil that originally had 0.2% total omega-3 fatty acids or its blend with fish oil (17.9% omega-3) or flaxseed oil (42.1% omega-3) significantly improved all biochemical parameters of MHRS. There was no significant difference in the biochemical parameters among the different oil treated groups regardless of the omega-3 fatty acid content. This may point out to the potential profound effect of the volatile oil fraction of Nigella crude oil which may compensates for its low omega-3 content. KEYWORDS: Hepatorenal syndrome; Nigella crude oil; Oil blends; Omega-3 fatty acidsRESUMEN: Evaluación del efecto terapéutico del aceite crudo de Nigella sativa y su mezcla con aceites ricos en ácidos grasos omega-3 en un modelo de síndrome hepatorenal modificado en ratas. En el presente estudio, el efecto hepato-y reno-protector de aceites crudos de Nigella sativa y su mezcla binaria con aceites ricos en ácidos grasos omega-3 (pescado y aceites de linaza) fue estudiado en un modelo modificado de síndrome hepatorenal (MHRS) en ratas. MHRS fue inducido a través de la alimentación de una dieta alta en fructosa seguido de la inyección intraperitoneal de clorhidrato de galactosamina. Diferentes aceites fueron suministrados como dosis oral diaria a ratas con MHRS. Se realizaron dos grupos de control de MHRS y ratas sanas normales. Se evaluaron diferentes parámetros bioquímicos y nutricionales. La inducción de la MHRS produce disfunción hepática y renal, elevado estrés oxidativo y biomarcadores inflamatorios, endotelina 1, y colesterol en plasma. Se observó una reducción del colesterol plasmatico de lipoproteínas de alta densidad, albúmina y Ca, elevación en orina de N-acetil-β-D-glucosaminidasa y de la grasa del hígado. La administración de aceite crudo de Nigella que tiene un 0,2% de ácidos grasos omega-3 totales o su mezcla con aceite de pescado (17,9% de omega-3) o aceite de linaza (42,1% de omega-3) mejoró significativamente todos los parámetros bioquímicos de MHRS. No hubo diferencia significativa en los parámetros bioquímicos entre los diferentes grupos tratados con los aceites ensayados independientemente del contenido de áci...

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Section: Discussionsupporting

confidence: 65%

Evaluation of the therapeutic effect of <em>Nigella sativa</em> crude oil and its blend with omega-3 fatty acid-rich oils in a modified hepatorenal syndrome model in rats

et al. 2015

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“…Putting these observations together, like a jigsaw puzzle, the missing piece becomes the following: can a more severe degree of inflammation and/or lesser tolerance to it affect the development of a type of kidney damage other than that of HRS? It has been observed in clinical [17] as well as in experimental studies [18] that in cirrhosis and superimposed infection/inflammation, an up-regulation of renal tubular TLR4 may occur, associated with the development of florid renal dysfunction with tubular damage and apoptosis. Renal dysfunction in these patients is associated with significant tubular injury and apoptosis and with increased renal expression and urinary excretion of the TLR4, suggesting a potential role of TLR4 as mediator of renal injury [17].…”

Section: Pathogenesis Of Sepsis Induced-akimentioning

confidence: 98%

“…It has been observed in clinical [17] as well as in experimental studies [18] that in cirrhosis and superimposed infection/inflammation, an up-regulation of renal tubular TLR4 may occur, associated with the development of florid renal dysfunction with tubular damage and apoptosis. Renal dysfunction in these patients is associated with significant tubular injury and apoptosis and with increased renal expression and urinary excretion of the TLR4, suggesting a potential role of TLR4 as mediator of renal injury [17]. Although the mechanism of up regulation of tubular TLR4 is not entirely clear, it seems likely to be a consequence of the continuous exposure to gut bacterial translocation [17] and may be prevented by gut decontamination with norfloxacin [18].…”

Section: Pathogenesis Of Sepsis Induced-akimentioning

confidence: 98%

Sepsis-induced acute kidney injury in patients with cirrhosis

et al. 2015

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Acute kidney injury (AKI) is a common and life-threatening complication in patients with cirrhosis. Recently, new criteria for the diagnosis of AKI have been proposed in patients with cirrhosis by the International Club of Ascites. Almost all types of bacterial infections can induce AKI in patients with cirrhosis representing its most common precipitating event. The bacterial infection-induced AKI usually meets the diagnostic criteria of hepatorenal syndrome (HRS). Well in keeping with the "splanchnic arterial vasodilation hypothesis", it has been stated that HRS develops as a consequence of a severe reduction of effective circulating volume related to splanchnic arterial vasodilation and to an inadequate cardiac output. Nevertheless, the role of bacterial infections in precipitating organ failures, including renal failure, is enhanced when their course is characterized by the development of a systemic inflammatory response syndrome (SIRS), thus, when sepsis occurs. Sepsis has been shown to be capable to induce "per se" AKI in animals as well as in patients conditioning also the features of renal damage. This observation suggests that when precipitated by sepsis, the pathogenesis and the clinical course of AKI also in patients with cirrhosis may differentiate to a certain extent from AKI with another or no precipitating factor. The purpose of this review is to describe the features of AKI precipitated by bacterial infections and to highlight whether infection and/or the development of SIRS may influence its clinical course, and, in particular, the response to treatment.

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“…Kim-1 is a member of the immunoglobulin family and is expressed in the surface of activated T cells (CD4 + Th2) (32); therefore, sKim-1 may be involved in the immune response to sepsis and its level is higher than normal in this condition. Previous animal and clinical studies have demonstrated (33,34) that Kim-1 is an inflammation mediator associated with the pathogenesis of asthma and rheumatoid arthritis. A prospective, multicenter cohort study (35) found that Kim-1 peaked at 2 days after cardiac surgery in adults and at 1 day after surgery in children, and that the elevations of Kim-1 were associated with AKI and adverse outcomes in adults.…”

Section: Group a (N=17) Group B (N=21) ------------------------------mentioning

confidence: 99%

Effect of continuous renal replacement therapy on kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in patients with septic acute kidney injury

Shao

Fan

Yin

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) have been investigated as biomarkers for acute kidney injury (AKI). However, they are seldom investigated in patients with septic AKI treated with continuous renal replacement therapy (CRRT). The aim of the present study was to investigate the therapeutic effectiveness and possible mechanisms of CRRT in septic AKI by observing the changes in Kim-1 and NGAL levels. A group of 38 patients with septic AKI was randomly divided into the conventional drug treatment group (group A) and the CRRT group (group B). All patients were treated with standard antisepsis agents, and group B was additionally submitted to CRRT for 24 h. The levels of Kim-1 and NGAL in serum, urine and the ultrafiltrate of CRRT were measured prior to and at 12, 24, and 48 h after treatment. In group A, urinary Kim-1 (uKim-1) levels at 12, 24 and 48 h were lower than prior to treatment (P<0.05), whereas urinary NGAL (uNGAL) showed no difference among the various time points (P>0.05). In group B, uKim-1 was decreased at 24 and 48 h compared with before treatment (all P<0.05), whereas uNGAL was decreased at 48 h (P<0.05). Serum Kim-1 did not change with time in groups A and B (P>0.05), whereas serum NGAL was increased after treatment in group A (P<0.05) but did not change in group B (P>0.05). Kim-1 and NGAL were not detected in the ultrafiltrate of CRRT. uKim-1 and uNGAL decreased significantly after CRRT, and therefore may be used to reflect the change of renal function during CRRT and to evaluate the therapeutic effectiveness of the method.

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Increased renal expression and urinary excretion of TLR4 in acute kidney injury associated with cirrhosis

Cited by 114 publications

References 33 publications

Evaluation of the therapeutic effect of <em>Nigella sativa</em> crude oil and its blend with omega-3 fatty acid-rich oils in a modified hepatorenal syndrome model in rats

Evaluation of the therapeutic effect of <em>Nigella sativa</em> crude oil and its blend with omega-3 fatty acid-rich oils in a modified hepatorenal syndrome model in rats

Sepsis-induced acute kidney injury in patients with cirrhosis

Effect of continuous renal replacement therapy on kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in patients with septic acute kidney injury

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