The Diagnostic Role of Urinary N-Acetyl-β-D-glucosaminidase (NAG) Activity in the Detection of Renal Tubular Impairment

Skálová, Sylva

doi:10.14712/18059694.2018.35

Cited by 95 publications

(91 citation statements)

References 69 publications

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“…Urinary NAG was significantly elevated in the MHRS model in the present study reflecting tubular dysfunction and kidney parenchymal damage as reported by Skálová (2005). In agreement with this result, high urinary NAG was reported in infants with liver cirrhosis (Aydogdu et al, 2004) pointing to an occurrence of renal dysfunction and HRS.…”

Section: Discussionsupporting

confidence: 92%

“…The increased plasma creatinine and reduced creatinine clearance in MHRS in the present study reflected that glomerular function, proximal tubules and glomerular filtration rate are affected in HRS as reported previously (Van Lente and Sult, 1989;Skálová, 2005). Renal dysfunction in patients with cirrhosis with superimposed inflammation was reported previously to be associated with significant tubular injury (Shah et al, 2013).…”

Section: Discussionsupporting

confidence: 88%

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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: 92%

Section: Discussionsupporting

confidence: 88%

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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“…The urinary content of another lysosomal enzyme, N-acetyl-␤-glucosaminidase, also known as ␤-hexosaminidase (130 kDa), is routinely used as a clinical marker for early detection of renal tubular impairment in glomerular disease (21) and is generally regarded as reflecting release from PTC. We propose to reassess the significance and usefulness of this assay.…”

Section: Discussionmentioning

confidence: 99%

Endocytosis provides a major alternative pathway for lysosomal biogenesis in kidney proximal tubular cells

Nielsen

Courtoy

Jacobsen

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Recruitment of acid hydrolases to lysosomes generally occurs by intracellular sorting based on recognition of a common mannose 6-phosphate signal in the transGolgi network and selective transport to late endosomes/lysosomes. Here we provide evidence for an alternative, efficient secretion-recapture pathway mediated by megalin and exemplified by cathepsin B in kidney proximal convoluted tubules (PCT). We found that in mouse kidneys with defective megalin expression [megalin knockout (KO)] or apical PCT trafficking (ClC-5 KO), the (pro)cathepsin B mRNA level was essentially preserved, but the protein content was greatly decreased and the enzyme was excreted in the urine as mannose 6-phosphate-devoid species. In polarized PCT-derived cells, purified cathepsin B was avidly and selectively taken up at the apical membrane, and uptake was abolished by the megalin competitor, receptor-associated protein. Direct interaction of cathepsin B with megalin was demonstrated by surface plasmon resonance. Procathepsin B was detected in normal mouse serum. Purified cathepsin B injected into mice was efficiently taken up by kidneys (Ϸ10% of injection) and targeted to lysosomes where it remained active, as shown by autoradiography and subcellular fractionation. A single cathepsin B injection into cathepsin B KO mice could reconstitute full lysosomal enzyme activity in the kidneys. These findings demonstrate a pathway whereby circulating lysosomal enzymes are continuously filtered in glomeruli, reabsorbed by megalinmediated endocytosis, and transferred into lysosomes to exert their function, providing a major source of enzymes to PCT. These results also extend the significance of megalin in PCT and have several physiopathological and clinical implications.lysosomes ͉ mannose 6-phosphate ͉ megalin ͉ cathepsin B

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“…1 With a molecular mass of 130-140 kDa, circulating NAG is not filtered through the glomeruli. In the kidneys, NAG is found predominantly in lysosomes of proximal tubular cells, and the small amount of NAG normally present in the urine is secreted by these cells by exocytosis.…”

mentioning

confidence: 99%

N-Acetyl-β-D-Glucosaminidase Does Not Enhance Prediction of Cardiovascular or All-Cause Mortality by Albuminuria in a Low-Risk Population

Solbu

Toft

Løchen

et al. 2016

Journal of the American Society of Nephrology

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Albuminuria is a well known risk factor for cardiovascular disease and mortality, but focus on renal tubular dysfunction as a potential risk factor is growing also. The association between the urinary activity of N-acetylb-D-glucosaminidase (NAG) and cardiovascular risk has been assessed mostly in cross-sectional studies. We studied the cross-sectional associations between urinary NAG and cardiovascular risk factors and the longitudinal associations between NAG, cardiovascular disease, and all-cause mortality in a general population. Urinary NAG/creatinine ratio (NAG ratio) and albumin/creatinine ratio (ACR) were measured in 6834 participants of the Tromsø Study in 1994-1995. During the median 17.5 years of follow-up, 958 myocardial infarctions, 726 ischemic strokes, and 2358 deaths were registered. In multivariable analyses adjusted for albuminuria and cardiovascular risk factors, a baseline NAG ratio in the highest quartile was associated with an increased risk of myocardial infarction (hazard ratio [HR], 1.43; 95% confidence interval [95% CI], 1.16 to 1.76), ischemic stroke (HR, 1.41; 95% CI, 1.10 to 1.80), and all-cause mortality (HR, 1.60; 95% CI, 1.39 to 1.84). Combined, ACR and NAG ratio above median associated with a 48%-80% increased risk for the three end points. However, the NAG ratio did not add significantly to the baseline risk-prediction models when assessed by area under the receiver operating characteristics curve or net reclassification improvement. In conclusion, the nonsignificant improvement of risk prediction does not support the clinical use of NAG ratio in cardiovascular risk assessment in a low-risk group.

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The Diagnostic Role of Urinary N-Acetyl-β-D-glucosaminidase (NAG) Activity in the Detection of Renal Tubular Impairment

Cited by 95 publications

References 69 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

Endocytosis provides a major alternative pathway for lysosomal biogenesis in kidney proximal tubular cells

N-Acetyl-β-D-Glucosaminidase Does Not Enhance Prediction of Cardiovascular or All-Cause Mortality by Albuminuria in a Low-Risk Population

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