Dataset Information

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

ABSTRACT: 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-acetyl-?-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.

SUBMITTER: Solbu MD

PROVIDER: S-EPMC4731108 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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

Solbu Marit D MD Toft Ingrid I Løchen Maja-Lisa ML Mathiesen Ellisiv B EB Eriksen Bjørn O BO Melsom Toralf T Njølstad Inger I Wilsgaard Tom T Jenssen Trond G TG

Journal of the American Society of Nephrology : JASN 20150605 2

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-acetyl-β-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- ...[more]

PMID: 26047791

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Project description:Neuronal cell bodies, isolated in bulk from 8-day-old rat cerebral cortices, were incubated in the presence of a 3H-labelled amino acid mixture, and subcellular fractions isolated by differential centrifugation. The particulate fractions were frozen/thawed in 0.20 M-sucrose/0.1 M-KCl [Selling et al. (1973) Biochim. Biophys. Acta 315, 128-146] and the profiles of acid-insoluble radioactivity and N-acetyl-beta-D-glucosaminidase (glucosaminidase) activity compared in the resulting non-sedimentable fractions by DEAE-cellulose chromatography and cellulose acetate electrophoresis. Radioactivity and glucosaminidase activity co-migrated to a significant extent. Electrophoresis revealed that after 1 min of incubation 42% of the radioactivity of the non-sedimentable microsomal fraction after freezing and thawing co-migrated with an intensely fluorescent band of glucosaminidase activity. Since the pellet fraction obtained on freezing/thawing the microsomal fraction contained up to 75% of the RNA, 95% of the radioactivity and 45% of the glucosaminidase, a detailed study of the association between its radioactivity and nascent glucosaminidase activity was undertaken. After 1 and 2 min of incubation, followed by centrifugation of the microsomal pellet on 35-60% (w/v) sucrose density gradients, radioactivity and glucosaminidase activity exhibited parallel profiles in the region of heavy polyribosomes and at the top of the gradient which contains spontaneously released nascent polypeptide chains. DEAE-cellulose chromatography of these chains revealed glucosaminidase A to be the principal nascent glucosaminidase component, with glucosaminidases B and C as minor peaks. After 2 min of incubation, all of the glucosaminidase components appeared labelled, and glucosaminidase A exhibited two distinct sub-components. The pattern of glucosaminidase labelling in the soluble and microsomal fractions suggested that newly formed glucosaminidase molecules traverse both the cellular sap and the lumen of the endoplasmic reticulum. Only glucosaminidase A reacted specifically with concanavalin A and radioactive glucosaminidase A could be successfully regenerated by treatment with alpha-methyl-D-glucoside. Glucosaminidase A and a substantial portion of the radioactivity associating with it could be readily converted into glucosaminidase B by re-chromatography on DEAE-cellulose and by reaction of the concanavalin A-glucosaminidase A complex with methyl glucosides.

Dataset Information

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

Publications

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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