Proteome of Human Urinary Exosomes in Diabetic Nephropathy

Abstract

Diabetic kidney disease (DKD) is the major complication in diabetic patients, the leading cause of end-stage renal disease (ESRD), and main risk factor for cardiovascular disease (CVD). Its silent development, together with the lack of specific and early accessible indicators of renal damage, often results in a late diagnosis when kidney damage is irreversible. Omics approaches (genomics, proteomics, metabolomics) account with the advantage of investigating the molecular milieu as a whole, without preselection of potential targets. The complexity and wide range of concentration levels of biological fluids as plasma, serum, or urine makes difficult the discovery of novel markers of kidney disease progression, other than already known high-abundance molecules (e.g., albumin). Exosomes are microvesicles derived from kidney cells in contact with the urinary space with proven roles in RNA and protein transfer and cell-cell communication. Exosomes may directly reflect pathophysiological changes taking place in the damaged kidney, constituting a feasible alternative to the invasive biopsy. Once released into urine or plasma, exosomes can be isolated and thus represent a sub-proteome where molecular messengers are enriched. This chapter overviews the current panorama in the potential use of exosomes as a novel source of biomarkers able to improve DKD current diagnosis, patients' risk stratification, and prognosis prediction.