Potential kidney biomarkers in urinary extracellular vesicles from end stage renal disease and post-transplant patients

Chronic kidney disease is a multifactorial entity characterized by decreased glomerular filtration rate (GFR). The last stage of the disease requires renal replacement therapy or kidney transplantation. As a disease with no treatment at earlier stages, and few biomarkers available, proteomics represent an excellent tool searching for new more efficient biomarkers. Urinary extracellular vesicles are an important source of information for kidney alterations, and their collection is not invasive. In this exploratory study, we worked on urine samples collected from patients at Centro Medico Nacional de Occidente in Guadalajara, Jalisco, and isolated urinary extracellular vesicles (uEVs) by ultracentrifugation. Our objective was to compare the Proteomic Profile of uEVs between Mexican patients with normal kidney function, end-stage renal disease, or kidney transplantation. High resolution mass spectrometry analysis reveals alterations in end-stage renal disease regarding the energy metabolism, cytoskeleton organization and cell motility. Proteomic alterations in transplant patients point towards the conservation of fibrotic process. Important proteins such as cystatins can be proposed as candidates for kidney transplant monitoring, while Gelsolin, a protein with an important role in assessing podocyte damage, stands out as a probable marker of chronic kidney disease. Data are available via ProteomeXchange with identifier PXD065380.

Significance

Chronic Kidney disease is a growing public health burden, increasing each year, and favored by major chronic diseases such as diabetes and hypertension. Although Mexico is one of the countries with the highest incidence of chronic kidney disease, proteomics studies involving Mexican patients had not yet been conducted. uEVs are features of particular interest to study the disease and discover biomarkers. We characterized the uEVs proteomic profile in Mexican patients, providing new insights into the pathogenesis of chronic kidney disease and kidney transplantation disorders. We identified promising biomarker candidates for transplant monitoring, and one as an early indicator of ESRD progression. uEVs may serve as a non-invasive platform for renal disease investigation, potentially offering non-invasive biomarkers for patient monitoring as well as mechanistic insights for future research into kidney pathophysiology.