Peer Review #1 of "The role of serum and urinary biomarkers in the diagnosis of early diabetic nephropathy in patients with type 2 diabetes (v0.2)"

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, along with 42 healthy controls. We assessed 13 biomarkers, including transferrin (Tf), immunoglobulin G (IgG), podocalyxin (PCX), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-beta-glucosaminidase (NAG), α-1microglobulin (α1MG), 8-hydroxy-deoxyguanosine (8-OHdG), tumor necrosis factor-alpha (TNF-α) , and interleukin-18 (IL-18) in urine samples, along with cystatin C (CysC), total bilirubin (TBIL) , and uric acid (UA) in sera samples, to evaluate their diagnostic roles. From the measurements, the blood neutrophil to lymphocyte ratio (NLR) 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 (ROC AUC) and found that urinary IgG (0.894), NGAL (0.875), Tf (0.861), TNF-α (0.763), and the combinations of urinary Tf + IgG + TNF-α + NGAL (0.922) showed good diagnostic value for early-stage DN. Conclusions: Urinary Tf, IgG , NGAL, and TNF-α, and the combination of all four biomarkers demonstrated excellent diagnostic value for early-stage DN in patients with type 2 diabetes.