Diabetes Metab J.  2022 Jan;46(1):104-116. 10.4093/dmj.2020.0273.

Renal Tubular Damage Marker, Urinary N-acetyl-β-D-Glucosaminidase, as a Predictive Marker of Hepatic Fibrosis in Type 2 Diabetes Mellitus

• Kim HK
• Lee M
• Lee Yh
• Kang ES
• Cha BS
• Lee BW

• KMID: 2525130
• DOI: http://doi.org/10.4093/dmj.2020.0273

Abstract

Background
Non-alcoholic steatohepatitis is closely associated with the progression of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). We investigated whether urinary N-acetyl-β-D-glucosaminidase (u-NAG), an early renal tubular damage biomarker in DKD, could be related to the degree of hepatic fibrosis in patients with T2DM.
Methods
A total of 300 patients with T2DM were enrolled in this study. Hepatic steatosis and fibrosis were determined using transient elastography. The levels of urinary biomarkers, including u-NAG, albumin, protein, and creatinine, and glucometabolic parameters were measured.
Results
Based on the median value of the u-NAG to creatinine ratio (u-NCR), subjects were divided into low and high u-NCR groups. The high u-NCR group showed a significantly longer duration of diabetes, worsened hyperglycemia, and a more enhanced hepatic fibrosis index. A higher u-NCR was associated with a greater odds ratio for the risk of higher hepatic fibrosis stage (F2: odds ratio, 1.99; 95% confidence interval [CI], 1.04 to 3.82). Also, u-NCR was an independent predictive marker for more advanced hepatic fibrosis, even after adjusting for several confounding factors (β=1.58, P<0.01).
Conclusion
The elevation of u-NAG was independently associated with a higher degree of hepatic fibrosis in patients with T2DM. Considering the common metabolic milieu of renal and hepatic fibrosis in T2DM, the potential use of u-NAG as an effective urinary biomarker reflecting hepatic fibrosis in T2DM needs to be validated in the future.

Keyword

Acetylglucosaminidase; Diabetes mellitus, type 2; Non-alcoholic fatty liver disease; Liver cirrhosis

Figure

• 

  Fig. 1. Odds ratios for hepatic steatosis and fibrosis stages based on urinary N-acetyl-β-D-glucosaminidase to creatinine ratio (u-NCR). (A) No significant association between u-NCR and any stage of hepatic steatosis was observed. (B) Odds ratio in each stage of hepatic fibrosis increased as the stages advanced: F2 (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.04 to 3.82; P=0.039), F3 and F4 (OR, 2.40; 95% CI, 1.52 to 3.80; P<0.001) (multivariate logistic regression Model 4 in Supplementary Tables 2 and 3).

• 

  Fig. 2. Median urinary markers based on hepatic fibrosis stages. (A) Median value of urinary N-acetyl-β-D-glucosaminidase to creatinine ratio (u-NCR) was higher in F2 (8.01 [4.65 to 14.68] vs. 5.94 [3.77 to 9.33], P=0.045), F3 (9.20 [6.78 to 12.81] vs. 5.94 [3.77 to 9.33], P=0.002), and F4 (9.44 [5.04 to 14.31] vs. 5.94 [3.77 to 9.33], P=0.001), compared with that in F0 (5.94 [3.77 to 9.33]). (B) The median of urinary albumin to creatinine ratio (u-ACR) showed no significant difference in any hepatic fibrosis stages. The asterisks denote the significance levels compared with F0 and F1 (control group) using the Mann-Whitney U test. NS, non-specific. aP<0.05.

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  Fig. 3. Graphical abstract of urinary N-acetyl-β-D-glucosaminidase and hepatic fibrosis in patients with type 2 diabetes mellitus (T2DM).

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