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      Distribution of urinary N‐acetyl‐beta‐D‐glucosaminidase and the establishment of reference intervals in healthy adults


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          Urinary N‐acetyl‐beta‐D‐glucosaminidase (NAG) plays an important role in the early diagnosis and progression of diseases related to renal tubular injury. We detected the urinary NAG concentration, assessed the preliminary statistics of its distribution, and established reference intervals for healthy adults in China using the rate method.


          A total of 1,095 reference individuals (aged 20 to 79 years) met the requirements for inclusion in this study. Urinary NAG concentrations were detected using an AU5800 automatic biochemical analyzer with its matched reagents. The Kolmogorov‐Smirnov test was used to analyze the normality of the data. According to the guidelines of C28‐A3 and WS/T 402‐2012, the reference intervals of urinary NAG were established using the nonparametric percentile method (unilateral 95th percentile).


          The urinary NAG data showed a non‐normal distribution. The distribution of urinary NAG was significantly different by sex and age. Therefore, the reference intervals of urinary NAG were established using the rate method: males (aged 20–59 years) <19.4 U/L (90% CI: 18.0–20.3 U/L); males (aged 60–79 years) <22.3 U/L (90% CI: 20.2–22.6 U/L); females (aged 20–59 years) <15.7 U/L (90% CI: 15.2–16.5 U/L); and females (aged 60–79 years) <21.4 U/L (90% CI: 20.3–22.3 U/L).


          We established preliminary reference intervals of urinary NAG for healthy adults in China to provide guidance for health screening, auxiliary diagnosis, and treatment monitoring of renal tubule‐related diseases.


          Establishing reference intervals of urinary NAG on the basis of C28‐A3.

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          Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

          Diabetic nephropathy (DN) is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-beta-glucosaminidase (NAG), alpha-1 microglobulin (A1M), beta 2-microglobulin (B2-M), and retinol binding protein (RBP) associated with early DN.
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            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

            Background To 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. Methods A 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. Results We 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. Conclusions Elevated 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 material The 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 N -acetyl-beta- d -glucosaminidase (NAG) with neutrophil gelatinase-associated lipocalin (NGAL) improves the diagnostic value for proximal tubule damage in diabetic kidney disease

              Screening for diabetic kidney disease (DKD) remains a challenge; however, there has been an ongoing research to investigate the diagnostic value of different biomarkers to identify DKD. The aim of this study was to assess the diagnostic value of both N -acetyl-beta- d -glucosaminidase (NAG) and neutrophil gelatinase-associated lipocalin (NGAL) in the progression of DKD. This cross-sectional case–control study included 92 type 2 diabetic patients with or without DKD. Urinary NAG and NGAL were measured to evaluate their diagnostic values as biochemical markers related to DKD. Both urinary NAG and NGAL levels were significantly higher among patients with DKD. In multiple linear regression analysis, NAG showed a positive significant association with NGAL in the three different adjusted models, while no significant correlation with fasting blood glucose, glycated hemoglobin, serum creatinine, estimated glomerular filtration rate, and albumin creatinine ratio were observed. The area under the curve for NGAL was 0.659 ( p  = 0.01) and 0.564 ( p  = 0.297) for NAG in DKD patients. This study demonstrates the association between urinary NAG and NGAL as a tubular damage marker for DKD although longitudinal studies are needed to evaluate its diagnostic value.

                Author and article information

                J Clin Lab Anal
                J Clin Lab Anal
                Journal of Clinical Laboratory Analysis
                John Wiley and Sons Inc. (Hoboken )
                11 March 2021
                May 2021
                : 35
                : 5 ( doiID: 10.1002/jcla.v35.5 )
                : e23748
                [ 1 ] Department of Laboratory Medicine The Second People's Hospital of Lianyungang Lianyungang China
                Author notes
                [*] [* ] Correspondence

                Fumeng Yang, Department of Laboratory Medicine, The Second People's Hospital of Lianyungang, Lianyungang, China.

                Email: yfm31095018@ 123456163.com

                Author information
                © 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                : 17 February 2021
                : 11 January 2021
                : 22 February 2021
                Page count
                Figures: 3, Tables: 3, Pages: 6, Words: 3376
                Funded by: Research funding was from the Bengbu Medical College
                Award ID: BYKY18178
                Funded by: Jiangsu Commission of Health
                Award ID: M2020079
                Funded by: Key Project of Scientific Research Development Fund of Kangda College of Nanjing Medical University
                Award ID: KD2019KYJJZD011
                Research Article
                Research Articles
                Custom metadata
                May 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:17.05.2021

                Clinical chemistry
                healthy adults,reference interval,urinary n‐acetyl‐beta‐d‐glucosaminidase


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