The role of serum and urinary biomarkers in the diagnosis of early diabetic nephropathy in patients with type 2 diabetes

Abstract

Background Previous studies have shown that a variety of biomarkers are closely related to the occurrence and development of early-stage diabetic nephropathy (DN) in patients. The aim of this study was to evaluate the role of multiple sera and urinary biomarkers in the diagnosis of early-stage DN in patients with type 2 diabetes. Methods We enrolled 287 patients with type 2 diabetes, who were classified into normoalbuminuria (n = 144), microalbuminuria (n = 94), or macroalbuminuria (n = 49) groups based on their urine albumin to creatinine ratios (UACR), along with 42 healthy controls. We assessed 13 biomarkers, including transferrin (Tf), immunoglobulin G (IgG), podocalyxin, neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-beta-glucosaminidase, α-1-microglobulin, 8-hydroxy-deoxyguanosine, tumor necrosis factor-alpha (TNF-α), and interleukin-18 in urine samples, along with cystatin C, total bilirubin, and uric acid in sera samples, to evaluate their diagnostic roles. From the measurements, the blood neutrophil to lymphocyte ratio was also calculated. Results Urinary Tf, IgG, NGAL, and TNF-α were significantly related to the UACR. We calculated the area under the receiver operating characteristic curves (area under the curve) and found that urinary IgG (0.894), NGAL (0.875), Tf (0.861), TNF-α (0.763), and the combination of urinary Tf + IgG + TNF-α + NGAL (0.922) showed good diagnostic value for early-stage DN. Conclusions Urinary Tf, IgG, NGAL, TNF-α, and the combination of all four biomarkers demonstrated excellent diagnostic value for early-stage DN in patients with type 2 diabetes.

Evaluation of urinary biomarkers for prediction of diabetic kidney disease: a propensity score matching analysis

“…22 Recently, intensive cross-sectional studies demonstrated that they were significantly positively correlated with increased risk of DKD. 23–25 The results of our project were consistent with those of previous investigations. Moreover, the prognostic abilities of TF and IgG evaluated in this study were concordant with previous reports.…”

Oxidative Stress Markers in Chronic Kidney Disease with Emphasis on Diabetic Nephropathy

“…The exact pathogenesis is complex and oxidative stress has a significant role in the pathogenesis of DN and its progression to ESRD. In recent years, a variety of biomarkers of oxidative stress associated with DN has been found and the most important ones used in clinical studies are presented ( Table 2 ) [ 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 ].…”

“…Urinary 8-OHdG levels in type 2 diabetic patients were significantly higher in patients with macroalbuminuria compared to patients with micro- or normoalbuminuria [ 132 , 174 ]. Additionally, urinary 8-OHdG levels were increased in type 2 diabetic patients with micro- and macroalbuminuria compared to patients with normoalbuminuria and healthy controls; 8-OHdG levels were also significantly higher in patients with macroalbuminuria compared to patients with microalbuminuria [ 175 ]. In a prospective longitudinal study, patients with higher urinary excretion of 8-OHdG had a significant progression of DN compared to patients with moderate or lower excretion of 8-OHdG [ 176 ].…”

Renal expression of cytokines and chemokines in diabetic nephropathy

“…Patients with DN have a predominance of increased plasmatic and urinary levels of inflammatory mediators, both in early and end stages of the disease [9][10][11][12][13]. However, the extent of renal damage caused by immune cellderived cytokines and chemokines and the importance of such inflammatory mechanisms on the development and progression of DN requires further investigation [14,15].…”