Urinary Extracellular Vesicles for Diabetic Kidney Disease Diagnosis

Abstract

Diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD) in developed countries, affecting more than 40% of diabetes mellitus (DM) patients. DKD pathogenesis is multifactorial leading to a clinical presentation characterized by proteinuria, hypertension, and a gradual reduction in kidney function, accompanied by a high incidence of cardiovascular (CV) events and mortality. Unlike other diabetes-related complications, DKD prevalence has failed to decline over the past 30 years, becoming a growing socioeconomic burden. Treatments controlling glucose levels, albuminuria and blood pressure may slow down DKD evolution and reduce CV events, but are not able to completely halt its progression. Moreover, one in five patients with diabetes develop DKD in the absence of albuminuria, and in others nephropathy goes unrecognized at the time of diagnosis, urging to find novel noninvasive and more precise early diagnosis and prognosis biomarkers and therapeutic targets for these patient subgroups. Extracellular vesicles (EVs), especially urinary (u)EVs, have emerged as an alternative for this purpose, as changes in their numbers and composition have been reported in clinical conditions involving DM and renal diseases. In this review, we will summarize the current knowledge on the role of (u)EVs in DKD.

Extracellular vesicles of human diabetic retinopathy retinal tissue and urine of diabetic retinopathy patients are enriched for the junction plakoglo bin protein

“…Our functional analysis of proteins detected in DR retinal tissue derived EVs showed a strong correlation to remodeling of epithelial adherent junctions, which is closely related to epithelial migration and permeability (43). Recent studies from Gurudas et al (44) proposed serum cystatin C as a biomarker for sight-threatening diabetic retinopathy, but they do not consider the potential advantages of EVs as robust biomarkers (21). JUP, also known as junction plakoglobin or gamma-catenin, is a member of the catenin protein family, a component of desmosomes and adherent junction structures (45).…”

“…Retina conditioned media and retina were collected after five days for analysis. Urine samples were collected after patient consent, stored, and treated as previously described (21). Patient characteristics and application are depicted in Table 1 (human retina samples) and Table 2 (human urine samples).…”

A Deep Insight Into Regulatory T Cell Metabolism in Renal Disease: Facts and Perspectives

“…In patients with lgAN, the level of abnormally glycosylated circulating IgA increases, which induces the formation of autoantibodies of IgA and IgG and then forms a circulating immune complex of autoantibodies of IgA and lgG (338). These immune complexes contribute to mesangial cell proliferation and excessive production of extracellular matrix, cytokines, and chemokines, eventually leading to glomerular sclerosis (11,19,(339)(340)(341).…”

“…It is well known that renal disease is accompanied by significant changes in metabolic patterns ( 11 ), such as changes in glucose ( 12 ), amino acid ( 13 ), and lipid metabolism ( 14 ), which are essential for the activation and proliferation of Treg cells. Moreover, the metabolic pattern of Treg cells is also regulated by the metabolic state of nephropathy, and the type of nutrients used by Treg cells in nephropathy changes their differentiation, resulting in alterations in their phenotype and proportion.…”

Production and internalization of extracellular vesicules in normal and under conditions of hyperglycemia and insulin resistance

“…Идентифицировано несколько микроРНК в мочевых ВВ, ассоциированных с диабетической нефропатией и ренальным фиброзом. Кроме того, выявлены экзосомальные микроРНК в циркулирующих экзосомах, ассоциированные с альбуминурией у пациентов с диабетической нефропатией [44][45][46].…”