The first finding of our study was the distribution of microvascular complications of diabetes in outpatients. Of the registered outpatients, approximately 61% were classified in the DR(-)UACR(-) group, 9% in the DR(+)UACR(-) group, and 25% in the DR(-) group. Classified. UACR(+), and 5% fall into the group DR(+)UACR(+). In these outpatient populations, approximately 14% of DR(+) patients showed significant differences in urinary marker measurements or positivity rates, regardless of the onset of retinopathy, suggesting that retinopathy and renal impairment in diabetic patients The occurrence suggests this may not necessarily be the case. They are closely related, at least in certain patients. Several studies have indicated that DR and DKD may be interrelated and influence each other. [17, 18]our study showed that a significant proportion of T2DM patients can develop the two conditions independently of each other.
The second finding was that even in patients with negative values for both DR and UACR, the positive detection rate of u-NAG/Cr reached 10.48%. It has been recognized that urinary NAG located on the lysosomes of renal tubular epithelial cells may reflect structural damage to the renal tubular epithelial cells. [19]. T2DM patients often have elevated u-NAG/Cr levels, possibly due to reabsorption overload, local inflammatory damage, and hypoxia. These conditions can precede glomerular injury. Previous studies also showed that u-NAG levels are proportional to non-albumin proteinuria levels in T2DM patients with DKD, even before the onset of overt albuminuria. [20]. In the UACR-positive group, the u-NAG/Cr positivity rate was close to 40%, indicating that the effects of diabetes on glomeruli and tubules are independent rather than coordinated and vary from person to person. This finding strongly suggests that it is important to include tubule-related markers in early screening for DKD. The susceptibility of T2DM patients to glomerular or tubular injury requires further investigation, and appropriate early intervention strategies also require further investigation.
The third finding was that u-IgG/Cr positivity was high even in people with negative values for both DR and UACR. Previous studies have suggested that increased urinary IgG reflects severe damage to the glomerular basement membrane. [21]. Increased urinary IgG excretion rate appears to indicate a decrease in estimated glomerular filtration rate (eGFR), which may be a marker of disease progression. [22]. However, several other studies have reported that urinary IgG may be elevated in diabetic patients before microalbuminuria or normoalbuminuria occurs. [23,24,25]This is consistent with our results. Increased urinary IgG excretion may be due to selective damage to glomerular pore size and increased intraglomerular water pressure caused by hyperglycemia. [26]. Urinary IgG is more sensitive than microalbuminuria in reflecting changes in renal hemodynamics and inflammation. [27]our findings suggest that urinary IgG can also be used as an early marker of diabetic kidney injury.
Our study also showed several abnormal increases in other urinary proteins, including both glomerular and tubular relative biomarkers. Data show that tubular reabsorption biomarkers (such as u-α1MG/Cr, u-β2MG/Cr, u-RBP/Cr, u-CysC/Cr) were increased in the DR and UACR double negative groups . This result suggests that in the early stages of diabetes, the reabsorption function of the proximal tubule is reduced, and low-molecular-weight proteins may be present in large amounts in the urine. [7]. The detection rates of tubular epithelial cell injury biomarkers (u-NGAL/Cr and u-NAG/Cr) were 4.03% and 10.48%, respectively. Inflammation, onset of stress, and increased reabsorption load due to hyperglycemia can exacerbate tubular lesions. These biomarkers may be useful in assessing the extent of renal tubular damage. [28, 29]. Management and prognosis based on these biomarkers may be clinically important and merit further study.
Ultimately, we found that the prevalence of specific biomarkers did not differ significantly between patients with different years of diabetes. It is observed that the top three biomarkers with high positivity rate are u-TRF/Cr, u-NAG/Cr, and u-IgG/Cr in both the <5 years diabetes group and other groups . This is also true for the DR(-)UACR (-) group. (See Figure 3, Supplementary Figure 1) Because it is difficult to accurately identify the onset of type 2 diabetes, we recommend that testing for albuminuria and tubular damage markers begin annually at the time of diabetes diagnosis. Masu. [16]. However, tubular markers may not be frequently measured in current clinical studies, leading to some degree of underestimation of their clinical importance. To more fully evaluate DKD, we propose that different panels of ductal biomarkers should be used to diagnose T2DM patients with different diabetes durations for different purposes.
This study has some limitations. First, this was a cross-sectional study that employed continuous and convenient recruitment and provided the distribution of nine urinary biomarkers only in people living with T2DM in a stable chronic state. Second, due to the limited conditions, we did not collect detailed medication information such as participants' medication history. eGFR and HbA1c results were collected for only a small number of participants. As a result, this study could not thoroughly discuss the correlation between eGRF, HbA1c, and nine biomarker results. Third, we did not determine the sample size range for this study. When planning this study, we set minimum standards and tried to enroll as many participants as possible within the time period. Additionally, this is a single-center study.
In summary, diabetic retinopathy and renal pathology may be independent, and retinopathy cannot be excluded even in seemingly normal UACR. Adding tubular markers to the screening list for DKD is necessary to fill the gap for UACR-negative people living with T2DM. Early detection of renal tubular biomarkers is important to adjust treatment strategies, protect renal function, and improve prognosis. To detect DKD at early stages, detection of both glomerular and tubular biomarkers is recommended.
