Urinary NAG-Creatine Ratio Predicts Advanced Diabetic Kidney Disease

Diabetes is the leading cause of chronic kidney disease and end-stage kidney disease worldwide and becomes one of the biggest healthcare challenges of the 21st century. Microvascular complications have been identified as the common and major diabetic complications.

Diabetic Kidney Disease (DKD) typically manifests a progressive deterioration of kidney function, and the increased glomerular filtration rate (GFR), glomerular hypertrophy, and excretion of urinary albumin are the major indicators. Various urine proteins may exhibit significant differences in diagnostic, predictive, and prognostic power for DKD.

Medical Scientists at the Suzhou Medical College of Soochow University (Suzhou, China) retrospectively analyzed a total of 117 patients with type 2 DKD, 83 males and 34 females, aged 37–85 years, including early and advanced stages and their laboratory parameters were statistically assessed. The patients were divided into two groups: early (stages IIa and IIb) and advanced (stages III and IV) groups based on the pathological grading.

The urine in spot time and whole 24 hours was obtained, and the fasting venous blood of patients were collected in vacutainer tubes. A BC-7500 automatic hematological analyzer (Mindray Inc, Shenzhen, China) was used to analyze the white blood cell (WBC), neutrophil (NEU), and high sensitive C reactive protein (HS-CRP). Multiple biochemical indexes were measured, which included serum creatine (sCR), serum urea (sUR), cholesterol (CHOL), homocysteine (HCY), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), fibrinogen (FIB), and d-dimer (D-D).

The levels of urinary creatinine, N-acetyl-β-d-glucosaminidase (NAG), total protein (PRO), microalbumin (MA), immunoglobulin G (IgG), transferrin (TFR), and α1-microglobulin (α1MG) in spot urine, and albumin excretion (UAE) in 24 hour urine were measured by the AU5800 fully automated biochemical analyzer (Beckman-Coulter, Brea, CA, USA). Urinary N-acetyl-β-d-glucosaminidase (NAG) and proteins to creatinine ratios were calculated to present as NAG/CR, PRO/CR, albumin to creatine ratio (ACR), IgG/CR, TFR/CR, and α1MG/CR.

The investigators reported that N-acetyl-β-d-glucosaminidase-creatine (NAG/CR) level in advanced DKD was statistically higher than that in early DKD, and there was a higher incidence of advanced DKD (72% versus 56%) and high odds ratio (OR: 3.917) of NAG/CR with ≥2.79 U/mmol compared with <2.79 U/mmol. NAG/CR ratio also showed a higher area under the ROC curve of 0.727 with a high sensitivity (0.75) and a moderate specificity (0.66) when 1.93 U/mmol was set as the optimal cutoff value. The adjusted-multivariable analysis revealed that NAG/CR had an OR of 1.021 and 2.223 based on a continuous and categorical variable, respectively, for risk of advanced DKD. Moreover, the prevalence of advanced DKD exhibited an increasing tendency by an increment of the trisector of NAG/CR.

The authors concluded that NAG/CR ratio is an independent predictor for advanced DKD in type 2 diabetes (T2D) patients, and it also can be used as a powerful identifying marker between early and advanced DKD. The study was published on December 26, 2022 in the Journal of Clinical Laboratory Analysis.

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