Integrating exosomal transcriptomics and soluble proteomics from urinary supernatant for early detection of diabetic nephropathy: a review

The present review assesses prior studies on glomerular-centric perspectives and conventional biomarkers, including microalbuminuria and estimated glomerular filtration rate. These diagnostic markers have limitations in the early detection of diabetic nephropathy in clinical practice. To overcome this diagnostic gap, recent evidence indicates that the nephron functions as an integrated paracrine network in which tubuloglomerular crosstalk is mediated by urinary extracellular vesicles, known as exosomes. These nanovesicles carry pathogenic signals throughout the nephron, thereby promoting spatiotemporal injury between the glomerular and tubular regions. To improve the study of orthograde and retrograde crosstalk mechanisms, it is recommended to replace rapidly degrading apoptotic cell sediment with cell-free urine supernatant to maintain transcriptomic stability. Additionally, a novel screening panel is proposed to detect intracellular scaffolding collapse by measuring exosomal podocin mRNA. The panel also monitors slit diaphragm shedding and dedifferentiation in proximal convoluted tubules by measuring soluble nephrin and kidney injury molecule-1 ectodomain, respectively. This precision technique has the potential to detect the clinically silent window of disease by integrating exosomal transcriptomic and soluble proteomic signatures from distinct cellular compartments. In conclusion, such approaches can redefine prognostic stratification and help avoid terminal glomerulosclerosis before functional decline becomes irreversible.