Urinary vitronectin identifies patients with high levels of fibrosis in kidney grafts
Carreras-Planella, Laura (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Cucchiari, David (Fundació Privada Clínic Per a La Recerca Biomèdica. Laboratori Experimental de Nefrologia i Trasplantament)
Cañas, Laura (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Juega-Mariño, Javier (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Franquesa, Marcella (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Bonet Sol, Josep (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Revuelta, Ignacio (Fundació Privada Clínic Per a La Recerca Biomèdica. Laboratori Experimental de Nefrologia i Trasplantament)
Diekmann, Fritz (Fundació Privada Clínic Per a La Recerca Biomèdica. Laboratori Experimental de Nefrologia i Trasplantament)
Taco, Omar (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Lauzurica, Ricardo (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Borràs i Serres, Francesc Enric (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)

Fecha:	2021
Resumen:	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. 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). 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). Urinary vitronectin levels are a potential stand-alone biomarker to monitor fibrotic changes in kidney transplant recipients in a non-invasive fashion. The online version of this article (10. 1007/s40620-020-00886-y) contains supplementary material, which is available to authorized users.
Ayudas:	Instituto de Salud Carlos III PI13/ 00050 Instituto de Salud Carlos III RD16/0009 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-301
Nota:	Altres ajuts: The project leading to these results has also received funding from "la Caixa" Foundation (ID 100010434), under agreement CI19-00048. This activity has received funding from the European Institute of Innovation and Technology (EIT). This body of the European Union receives support from the European Union's Horizon 2020 research and innovation program. LCP is sponsored by the Spanish Government FPU grant ("Formación de Personal Universitario", FPU17/01444). MF is supported by ISCIII (MS19/00018), co-funded by ERDF/ESF, "Investing in your future". FEB is a researcher from Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol, supported by the Health Department of the Catalan Government (Direcció General de Recerca i Innovació, Dept. Salut, Generalitat de Catalunya).
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Urinary extracellular vesicles ; Exosomes ; Biomarker fibrosis ; Nephrology ; Noninvasive
Publicado en:	Journal of Nephrology, Vol. 34 (2021) , p. 861-874, ISSN 1724-6059

DOI: 10.1007/s40620-020-00886-y
PMID: 33275196

14 p, 1.8 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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