Urinary vitronectin identifies patients with high levels of fibrosis in kidney grafts
- PDF / 1,902,246 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 88 Downloads / 155 Views
ORIGINAL ARTICLE
Urinary vitronectin identifies patients with high levels of fibrosis in kidney grafts Laura Carreras‑Planella1,2 · David Cucchiari3,4 · Laura Cañas1,5,6 · Javier Juega1,5,6 · Marcella Franquesa1,6 · Josep Bonet1,5,6 · Ignacio Revuelta3,4,7 · Fritz Diekmann3,4,7 · Omar Taco5,6 · Ricardo Lauzurica1,6,7 · Francesc Enric Borràs1,2,6,7 Received: 5 July 2020 / Accepted: 8 October 2020 © The Author(s) 2020
Abstract Background In kidney transplantation, fibrosis represents the final and irreversible consequence of the pathogenic mechanisms that lead to graft failure, and in the late stages it irremediably precedes the loss of renal function. The invasiveness of kidney biopsy prevents this condition from being frequently monitored, while clinical data are rather unspecific. The objective of this study was to find noninvasive biomarkers of kidney rejection. Methods We carried out proteomic analysis of the urinary Extracellular Vesicles (uEVs) from a cohort of kidney transplant recipients (n = 23) classified according to their biopsy-based diagnosis and clinical parameters as interstitial fibrosis and tubular atrophy (IFTA), acute cellular rejection (ACR), calcineurin inhibitors toxicity (CNIT) and normal kidney function (NKF). Results Shotgun mass spectrometry of uEV-proteins identified differential expression of several proteins among these different groups. Up to 23 of these proteins were re-evaluated using targeted proteomics in a new independent cohort of patients (n = 41) classified in the same diagnostic groups. Among other results, we found a differential expression of vitronectin (VTN) in patients displaying chronic interstitial and tubular lesions (ci and ct mean > 2 according to Banff criteria). These results were further confirmed by a pilot study using enzyme-linked immunosorbent assay (ELISA). Conclusion Urinary vitronectin levels are a potential stand-alone biomarker to monitor fibrotic changes in kidney transplant recipients in a non-invasive fashion. Keywords Urinary extracellular vesicles · Exosomes · Biomarker fibrosis · Nephrology · Noninvasive
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40620-020-00886-y) contains supplementary material, which is available to authorized users. * Francesc Enric Borràs [email protected] 1
2
3
REMAR‑IVECAT Group, “Germans Trias i Pujol Research Institute (IGTP)” Health Science Research Institute, Campus Can RutiCarretera de Can Ruti, Camí de les Escoles s/n, 08916 Badalona, Spain Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona, Bellaterra, Cerdanyola del Vallès, Barcelona, Spain
Kidney transplantation is the best renal replacement therapy for patients with end-stage kidney disease in terms of survival rates [1], cost-effectiveness [2] and patients’ 4
Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Fundació Privada Clínic Per a La Recerca Biomèdica (FCRB), Barcelona, Spain
5
Autonomous University of Barce
Data Loading...
