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

Abstract

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.

Nephroprotective Effects of Tetramethylpyrazine Nitrone TBN in Diabetic Kidney Disease

“…TBN treatment significantly lowered levels of blood triglycerides ( Figure 1K ) but not of cholesterol in STZ rats ( Figure 1L ). NAG, an early proximal tubular damage marker for the onset of DKD, is known to increase with hyperglycemia, even in normo-albuminuria conditions ( Hong N. et al, 2018 ). Urinary excretion of CysC suggests tubular injury as it is elevated in early stages of diabetes and DKD ( Garg et al, 2015 ; Uwaezuoke, 2017 ).…”

Codonopsis tangshen Oliv. Amelioration Effect on Diabetic Kidney Disease Rats Induced by High Fat Diet Feeding Combined with Streptozotocin

“…It is well accepted that hyperglycemia is the basic pathophysiological change in the tissue damage caused by DKD [ 12 , 13 ]. Persistent hyperglycemia results in insulin deficiency or resistance, thus impairing glucose metabolism.…”

Non-Albumin Proteinuria (NAP) as a Complementary Marker for Diabetic Kidney Disease (DKD)

“…Urinary NAG is very sensitive to tubular damage [ 12 , 57 ], and has been reported to exhibit higher sensitivity and specificity than albuminuria and creatinine clearance in patients with DM [ 58 ]. Interestingly, NAG is significantly associated with various glycemic parameters such as hyperglycemia and glycemic variability [ 57 , 59 , 60 ], and is a significant predictor of carotid artery atherosclerosis in DM [ 61 , 62 ]. These data findings suggest that urinary NAG reflects the severity of DM and its vascular complications.…”