Urinary FBP1 as a novel biomarker for the diagnosis and progression of diabetic nephropathy

Abstract Background: The pathogenesis of diabetic nephropathy (DN) is complex, and its onset is occult. It should be considered from multiple levels and angles using the concept of "system biology". New technologies, such as omics and high-throughput screening, provide more strategies for the screening of ideal markers of DN. Methods: we used data-independent acquisition (DIA) mass spectrometry for urine proteomic analysis of DN patients at different pathological stages and healthy controls. Results: Fructose-1,6-bisphosphatase 1 (FBP1) was specifically found in the urine of DN patients but not in that of healthy controls. Then, ELISA demonstrated that the urinary level of FBP1 in DN patients was significantly higher than that in healthy controls. We further verified the higher levels of urine FBP1 in association with DN than in association with type 2 diabetes mellitus (T2DM) and nondiabetic nephropathy. Receiver operating characteristic (ROC) curve analysis showed that FBP1 can distinguish DN and T2DM patients, and the AUC was 0.889 (sensitivity: 80%, specificity: 85%). Correlation analysis revealed that the level of urinary FBP1 was positively correlated with the progression of DN, as reflected by the fact that urinary FBP1 was negatively correlated with e-GFR and positively correlated with urea nitrogen, the interstitial inflammation score, and the interstitial fibrosis and tubular atrophy (IFTA) score. Conclusions: The source of urinary FBP1 was traced, and it was revealed that it was specifically reduced in proximal renal tubules with the progression of DN, supporting the view that urinary FBP1 can be used as a marker for the progression of diabetic nephropathy. Together, our results indicate that FBP1 might not only be a novel marker for the diagnosis of DN but also be a new marker for the progression of DN.