Urinary NAG is an essential predictor of diabetic nephropathy. Increased urinary NAG excretions may be detected in patients with early stages of diabetes mellitus even before any clinical evidence of kidney involvement .
In our study, the demographic data of both diabetic and healthy children were recruited, and they were similar (P > 0.05) except for body mass index (BMI), where diabetic children with microalbuminuria had significantly lower BMI than healthy children (P = 0.009).
This observation was not in concordance with other researchers , who found that BMI was slightly higher but statistically non-significant in all groups of patients as compared to healthy controls. Also, another study found that there is no significant difference in BMI between diabetic and healthy groups .
Our study revealed that diabetic children with microalbuminuria had a longer DM duration than diabetic children with normal uACR (P = 0.008) significantly.
This is in accordance with the results reported by . In their study, the disease duration was significantly longer in a group of patients with microalbuminuria and a group of patients with macroalbuminuria than in a group of patients with normoalbuminuric.
However, another study reported no significant difference between microalbuminuria and normoalbuminuric patients regarding the duration of diabetes (p = 0.12 and p = 0.406, respectively) .
In the present study, normoalbuminuric and microalbuminuria children have statistically significant differences in hypertension and neuropathy (P = 0.011 and P < 0.001, respectively).
The same result was reported in another study that systolic blood pressure (SBP) was significantly higher in microalbuminuria than in normoalbuminuric patients (P < 0.001) . Moreover, another study found that SBP was higher among those with microalbuminuria than normoalbuminuric subjects (P = 0.001) .
On the other hand, researchers found no statistically significant difference between both normoalbuminuric and microalbuminuria groups regarding blood pressure .
Our study confirmed that microalbuminuria diabetic children had significantly higher HbA1c levels than normoalbuminuric diabetic children (P < 0.001).
This agrees with another study that showed a significantly higher HbA1c level in macroalbuminuric and microalbuminuria diabetic patients than in normoalbuminuric diabetic patients, and healthy controls (P = 0.006) proved that poor glycemic control is a well-known risk factor for diabetic nephropathy .
Also, a study reported that microalbuminuria patients had significantly higher HbA1c than normoalbuminuric patients and healthy controls (P < 0.001) .
On the contrary, researchers found no statistically significant differences between microalbuminuria and normoalbuminuric groups regarding HbA1c .
In the present study, microalbuminuria diabetic children had significantly higher serum creatinine levels (P = 0.006) and urinary albumin creatinine ratio (P < 0.001) compared to normoalbuminuric diabetic children.
Similarly, a study showed that microalbuminuria T2DM patients with DKD had significantly higher serum creatinine and uACR than normoalbuminuric T2DM patients without DKD (P < 0.001 and P < 0.001, respectively) .
As shown in Bouvet et al. , the reported microalbuminuria group showed higher levels of ACR compared to the normoalbuminuric group (P < 0.001). They also found that there are no statistically significant differences between both groups regarding serum creatinine levels or eGFR.
In our study, microalbuminuria diabetic children had significantly higher serum HDL levels (P = 0.01) but substantially lower serum triglycerides levels (P = 0.002) compared to normoalbuminuric diabetic children.
Other studies analyzed different parameters of lipid profile; Suh et al.  reported that the lipid profiles did not differ between the normoalbuminuric and microalbuminuria groups, except for the total cholesterol level, which was significantly higher in the microalbuminuria group than in the normoalbuminuric group (P = 0.02).
In our study, uNAG was measured in the urine samples of all 90 children, where it was found that uNAG was significantly higher in all patients compared to the controls (P <0.001).
This is in accordance with the results reported by Omozee et al. . In these studies, the mean values of uNAG were higher in all patients with diabetes compared to the controls.
Both the mean and the median of uNAG were found to be significantly higher in the microalbuminuria group in comparison to the normoalbuminuric group (P < 0.001), and the mean and the median of uNAG level was higher in normoalbuminuric patients compared to controls (P < 0.001). Therefore, uNAG increased in parallel with the severity of renal disease, reaching higher levels in patients with manifest diabetic nephropathy.
Similarly, Mahfouz, Assiri, and Mukhtar  reported that the mean uNAG values in the microalbuminuria group were significantly high compared with normoalbuminuric patients. Also, Kim et al.  said that the uNAG level was higher in normoalbuminuric patients compared to controls.
In our study, there is a statistically significant positive correlation between urinary NAG (uNAG) and the duration of diabetes (P = 0.009, r = 0.334). This means that the more duration of diabetes, the higher the values of uNAG.
Similarly, Kim et al.  demonstrated that uNAG was positively correlated with the duration of diabetes and negatively correlated with BMI.
Patel and Kalia  reported that urinary NAG activity showed a non-significant increase in the early years of T2DM (0–5 and 5–10 years), and then it was significantly increased by 8 and 10 folds in 10–15 and 15–20 years of diabetes duration, respectively.
Recently, Siddiqui et al.  showed that NAG activity was increased with diabetes duration and with the progression of DKD.
Our study showed a highly statistically significant positive correlation between urinary NAG and HbA1c, uACR, and serum creatinine (P < 0.001, P < 0.001, and P = 0.005, respectively). Therefore, a strong relationship was reported between values of uNAG as a marker for diabetic nephropathy and HbA1c as a measure of glycemic control of diabetes. It is well described that poor glycemic control is a risk factor for most diabetic complications, among these is diabetic nephropathy.
In accordance with our study, Sheira et al.  typically revealed a significant positive correlation between urinary NAG level and albumin/creatinine ratio, serum creatinine, and HbA1c.
Similarly, Kim et al.  showed that urinary NAG had a positive relationship with urinary ACR (r = 0.458, P < 0.001). Also, uNAG and uACR were strongly correlated with HbA1c and serum creatinine. Also, Bouvet et al.  reported that there was a significant positive correlation between the NAG and urinary albumin/creatinine ratio (r = 0.74, P < 0.001).
Our study found a positive correlation between uNAG and serum cholesterol in the studied diabetic children (P = 0.026). The same was reported by Sheira et al. , who found a statistically significant correlation between uNAG and serum cholesterol. On the contrary, Sharifi et al.  did not find any correlation between uNAG and serum cholesterol.
Our results revealed a strong positive correlation between urinary NAG and urinary albumin creatinine ratio (uACR), where urinary NAG levels increase dramatically with an increase in uACR.
The positive correlation between uNAG and uACR was observed by many researchers [2, 3, 11]. On the other hand, Omozee, Okaka, and Edo  did not show any correlation between urinary microalbumin concentrations and urinary NAG concentrations.
Our results reported that the optimal sensitivity and specificity of uNAG were 96.7% and 96.7%, respectively, at a cut-off expression value > 1020 U/L. Urinary NAG helps differentiate between normoalbuminuric and microalbuminuria in diabetic children and has an essential predictive ability in diagnosing diabetic nephropathy.
Similarly, Patel and Kalia  revealed that the sensitivity and specificity of uNAG were 85.3% and 96%, respectively.
In our study, we elicited gender prevalence in uNAG values, where we found significantly higher uNAG in female patients than in male patients (P = 0.025). Similarly, a higher prevalence of microalbuminuria was observed in females (60%) compared to males (40%). A selection bias could not be excluded as female patients in our study represented 55.6% more than male patients, who represented only 44.4%, possibly due to the higher attendance rates of females than males in the DEMPU during the research period.
This is in accordance with the results reported by Sheira et al. , who revealed that the number of females with microalbuminuria (60%) was more than males (40%).
To summarize, we observed that uNAG positively correlates with ACR, duration of diabetes, HbA1c, serum creatinine, and serum cholesterol. Also, positive uNAG results were found even in normoalbuminuric patients, so it can be concluded that we can use uNAG as an early biomarker for diabetic nephropathy in normoalbuminuric patients, especially those with long-standing diabetes, uncontrolled diabetes, and dyslipidemia.
Our study has some limitations. First is the small number of the study. Second is the lack of follow-up of the uNAG after glycemic control and control of albuminuria.
Our study revealed that uNAG levels are significantly higher in microalbuminuric patients compared to normoalbuminuric patients and healthy controls. Also, in normoalbuminuric patients, there are high urinary levels of NAG. Our study also revealed a strong positive correlation between uNAG levels and the duration of diabetes. Measuring uNAG level is an easy and non-invasive biomarker for early detection of DN, especially for patients with type 1 diabetes with more than 2 years of uncontrolled diabetes. More extensive studies are recommended to correlate uNAG with other glomerular and tubular biomarkers of diabetes nephropathy.