Association Between Pulse Wave Velocity and a Marker of Renal Tubular Damage (<scp>N</scp>‐Acetyl‐β‐<scp>D</scp>‐Glucosaminidase) in Patients Without Diabetes

Ouchi, Motoshi; Oba, Koji; Saigusa, Taro; Watanabe, Kentaro; Ohara, Makoto; Matsumura, Noriaki; Suzuki, Tatsuya; Anzai, Naohiko; Tsuruoka, Shuichi; Yasutake, Masahiro

doi:10.1111/jch.12492

Cited by 10 publications

(10 citation statements)

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“…Even before the development of albuminuria, uNAG excretion was found to be positively correlated with hyperglycemia and diabetes duration 5 . Among our T1D subjects, the median uNAG level (5.6 U/g creatinine) fell within the reported range of values in various populations with diabetes (2.0–10.1 U/g creatinine), which was close to the range reported in a study of T1D subjects of similar age 18 , 23 – 25 . In accordance with previous findings, age was the most important determinant of uNAG level with significant linear correlation in this study, followed by poor glycemic control (A1c or GA level) and degree of albuminuria (ACR) in the submicroalbuminuric range.…”

Section: Discussionsupporting

confidence: 89%

“…uNAG was measured by an enzymatic method (Nittobo Medical, Fukushima, Japan) using a JCA-BM 6010/c automated chemistry analyzer (JEOL Ltd, Tokyo, Japan). A high uNAG level was defined using 5.8 U/g creatinine as a dichotomized cutoff, based on the upper normal value in a study of the Japanese population (normal range: 1.6 U/g to 5.8 U/g creatinine) 18 .…”

Section: Methodsmentioning

confidence: 99%

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Elevated urinary N-acetyl-β-D-glucosaminidase is associated with high glycoalbumin-to-hemoglobin A1c ratio in type 1 diabetes patients with early diabetic kidney disease

Hong

Lee

Park

et al. 2018

Sci Rep

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Urinary N-acetyl-β-D-glucosaminidase (uNAG) predicted the progression of diabetic kidney disease (DKD) prior to development of albuminuria in diabetes patients. We sought whether uNAG level is associated with glycoalbumin-to-hemoglobin A1c ratio (G/A ratio), a marker of postprandial hyperglycemia and glycemic excursion, independent of albuminuria and kidney function. The association between uNAG excretion and G/A ratio was assessed in 204 consecutive subjects with type 1 diabetes (T1D) (mean age 43.9 years; 49.0% men). uNAG excretion level increased along with older age, hyperglycemia, and degree of albuminuria, but was not correlated with body mass index or estimated glomerular filtration rate (eGFR). Elevated uNAG showed robust association with higher G/A ratio (adjusted β = 0.103, P = 0.020) after adjustment for age, sex, body mass index, duration of diabetes, uACR, angiotensin blockers use, fasting plasma glucose, and hemoglobin level. uNAG showed better discriminatory performance for individuals with high G/A ratio than albuminuria (AUC 0.613 vs. 0.518, P = 0.038). Measurement of uNAG improved AUC for high G/A ratio from 0.699 to 0.748 (P = 0.043) when added to conventional risk factors (cutoff 5.24 U/g creatinine; sensitivity 62.5% and specificity 58.0%). In conclusion, Elevated uNAG was found to be associated with high G/A ratio in patients with T1D with early stage DKD, independent of age and albuminuria.

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Section: Discussionsupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Elevated urinary N-acetyl-β-D-glucosaminidase is associated with high glycoalbumin-to-hemoglobin A1c ratio in type 1 diabetes patients with early diabetic kidney disease

Hong

Lee

Park

et al. 2018

Sci Rep

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“…That study investigated patients with T2D during a median follow-up of 7 years and showed that urinary NAG is comparable to albuminuria as an indicator of the preexistence and development of severe macrovascular disease, including myocardial infarction and peripheral vascular disease. Regarding subjects without diabetes, Ouchi et al [ 23 ] reported that elevated urinary NAG is related to elevated arterial stiffness assessed by brachial-ankle PWV. In a study including a low-risk general population, urinary NAG and ACR were independently associated with first-ever myocardial infarction, first-ever ischemic stroke, and all-cause mortality.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, increased urinary NAG is a sensitive marker of tubular injury related to inflammation and oxidative stress [ 24 ]. Therefore, the elevation of urinary NAG, a renal interstitial marker, might reflect the severity of interstitial changes that result from atherosclerosis and subsequent ischemic injury [ 23 ]. In addition, the association between urinary NAG and carotid IMT might be mediated by several common risk factors.…”

Section: Discussionmentioning

confidence: 99%

The renal tubular damage marker urinary N-acetyl-β-d-glucosaminidase may be more closely associated with early detection of atherosclerosis than the glomerular damage marker albuminuria in patients with type 2 diabetes

Kim

Lee

et al. 2017

Cardiovasc Diabetol

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BackgroundTo determine the association between urinary N-acetyl-β-d-glucosaminidase (NAG), a marker of renal tubulopathy, and carotid intima-media thickness (IMT) and plaques in patients with type 2 diabetes mellitus (T2D) and to compare the predictive value of NAG versus albuminuria, a marker of renal glomerulopathy.MethodsA total of 343 participants were enrolled in this retrospective cross-sectional study. We recruited participants with T2D who were tested for blood glucose parameters, urinary NAG, and urinary albumin-to-creatinine ratio (ACR) and had been checked for carotid ultrasonography.ResultsWe classified participants into a below-median urinary NAG group (Group I; n = 172) or an above-median group (Group II; n = 171). Mean, maximum, and mean of maximum carotid IMT and the proportion of patients with carotid plaques were significantly higher in Group II compared with Group I. In multiple linear regression analyses, high urinary NAG (Group II) was significantly associated with carotid IMT, independently of urinary ACR and other confounding factors. In terms of carotid plaques, both urinary NAG and ACR were significantly higher in participants with carotid plaques than in those without carotid plaques. After adjustment for confounding factors, both urinary NAG and ACR were significantly associated with the presence of carotid plaques.ConclusionsElevated urinary NAG, a marker of renal tubular damage, was related to increased carotid IMT and the presence of carotid plaques in patients with T2D. Urinary NAG may be a more sensitive biomarker than urinary albumin for early detection of atherosclerosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0497-7) contains supplementary material, which is available to authorized users.

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“…Urinary NAG, albumin, and glucose levels were expressed as uNAG-to-creatinine ratio and ACR to minimize the influence of variance in kidney function. Urinary NAG activity was considered abnormal when >5.8 U/g creatinine [ 10 ]. Urinary NAG was measured using a reagent from Nittobo Medial Co. Ltd. (Tokyo, Japan) and a JCA-BM 6010/c automated chemistry analyzer (JEOL Ltd., Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

Glycated Albumin Is a More Useful Glycation Index than HbA1c for Reflecting Renal Tubulopathy in Subjects with Early Diabetic Kidney Disease

et al. 2018

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BackgroundThe aim of this study was to investigate which glycemic parameters better reflect urinary N-acetyl-β-D-glucosaminidase (uNAG) abnormality, a marker for renal tubulopathy, in subjects with type 2 diabetes mellitus (T2DM) subjects with normoalbuminuria and a normal estimated glomerular filtration rate (eGFR).MethodsWe classified 1,061 participants with T2DM into two groups according to uNAG level—normal vs. high (>5.8 U/g creatinine)—and measured their biochemical parameters.ResultsSubjects with high uNAG level had significantly higher levels of fasting and stimulated glucose, glycated albumin (GA), and glycosylated hemoglobin (HbA1c) and lower levels of homeostasis model assessment of β-cell compared with subjects with normal uNAG level. Multiple linear regression analyses showed that uNAG was significantly associated with GA (standardized β coefficient [β]=0.213, P=0.016), but not with HbA1c (β=−0.137, P=0.096) or stimulated glucose (β=0.095, P=0.140) after adjusting confounding factors. In receiver operating characteristic analysis, the value of the area under the curve (AUC) for renal tubular injury of GA was significantly higher (AUC=0.634; 95% confidence interval [CI], 0.646 to 0.899) than those for HbA1c (AUC=0.598; 95% CI, 0.553 to 0.640), stimulated glucose (AUC=0.594; 95% CI, 0.552 to 0.636), or fasting glucose (AUC=0.558; 95% CI, 0.515 to 0.600). The optimal GA cutoff point for renal tubular damage was 17.55% (sensitivity 59%, specificity 62%).ConclusionGA is a more useful glycation index than HbA1c for reflecting renal tubulopathy in subjects with T2DM with normoalbuminuria and normal eGFR.

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Association Between Pulse Wave Velocity and a Marker of Renal Tubular Damage (N‐Acetyl‐β‐D‐Glucosaminidase) in Patients Without Diabetes

Cited by 10 publications

References 50 publications

Elevated urinary N-acetyl-β-D-glucosaminidase is associated with high glycoalbumin-to-hemoglobin A1c ratio in type 1 diabetes patients with early diabetic kidney disease

Elevated urinary N-acetyl-β-D-glucosaminidase is associated with high glycoalbumin-to-hemoglobin A1c ratio in type 1 diabetes patients with early diabetic kidney disease

The renal tubular damage marker urinary N-acetyl-β-d-glucosaminidase may be more closely associated with early detection of atherosclerosis than the glomerular damage marker albuminuria in patients with type 2 diabetes

Glycated Albumin Is a More Useful Glycation Index than HbA1c for Reflecting Renal Tubulopathy in Subjects with Early Diabetic Kidney Disease

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