Urinary Vitronectin Identifies Patients with High Levels of Fibrosis in Kidney Grafts

Overview

Journal J Nephrol

Publisher Springer

Specialty Nephrology

Date 2020 Dec 4

PMID 33275196

Citations 15

Authors

Laura Carreras-Planella

David Cucchiari

Laura Canas

Javier Juega

Marcella Franquesa

Josep Bonet

Ignacio Revuelta

Fritz Diekmann

Omar Taco

Ricardo Lauzurica

Francesc Enric Borras

Affiliations

Soon will be listed here.

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.

Citing Articles

Towards clinical translation of urinary vitronectin for non-invasive detection and monitoring of renal fibrosis in kidney transplant patients.

Clos-Sansalvador M, Taco O, Rodriguez-Martinez P, Garcia S, Font-Moron M, Bover J J Transl Med. 2024; 22(1):1030.

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Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches.

Welsh J, Goberdhan D, ODriscoll L, Buzas E, Blenkiron C, Bussolati B J Extracell Vesicles. 2024; 13(2):e12404.

PMID: 38326288 PMC: 10850029. DOI: 10.1002/jev2.12404.

Proteomic analysis investigating kidney transplantation outcomes- a scoping review.

Rainey A, Mckay G, English J, Thakkinstian A, Maxwell A, Corr M BMC Nephrol. 2023; 24(1):346.

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Physiopathological role of extracellular vesicles in alloimmunity and kidney transplantation and their use as biomarkers.

Cuadrado-Payan E, Ramirez-Bajo M, Banon-Maneus E, Rovira J, Diekmann F, Revuelta I Front Immunol. 2023; 14:1154650.

PMID: 37662919 PMC: 10469977. DOI: 10.3389/fimmu.2023.1154650.

Phosphoproteome Profiling of uEVs Reveals p-AQP2 and p-GSK3β as Potential Markers for Diabetic Nephropathy.

Li Q, Zhang J, Fang Y, Dai Y, Jia P, Shen Z Molecules. 2023; 28(14).

PMID: 37513479 PMC: 10383182. DOI: 10.3390/molecules28145605.

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