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Differential expression of microRNA miR-150-5p in IgA nephropathy as a potential mediator and marker of disease progression

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journal contribution
posted on 2021-07-06, 21:37 authored by IZA Pawluczyk, A Didangelos, SJ Barbour, L Er, JU Becker, R Martin, S Taylor, JS Bhachu, EG Lyons, RH Jenkins, D Fraser, K Molyneux, J Perales-Patón, J Saez-Rodriguez, J Barratt
Understanding why certain patients with IgA nephropathy progress to kidney failure while others maintain normal kidney function remains a major unanswered question. To help answer this, we performed miRNome profiling by next generation sequencing of kidney biopsies in order to identify microRNAs specifically associated with the risk of IgA nephropathy progression. Following sequencing and validation in independent cohorts, four microRNAs (-150-5p, -155-5p, -146b-5p, -135a-5p) were found to be differentially expressed in IgA nephropathy progressors compared to non-progressors, and patients with thin membrane nephropathy, lupus nephritis and membranous nephropathy, and correlated with estimated glomerular filtration rate, proteinuria, and the Oxford MEST-C scores (five histological features that are independent predictors of clinical outcome). Each individual microRNA increased the discrimination score of the International IgAN Prediction Tool, although due to the small number of samples the results did not reach statistical significance. miR-150-5p exhibited the largest amplitude of expression between cohorts and displayed the best discrimination between IgA nephropathy progressors and non-progressors by receiver operating curve analysis (AUC: 0.8). However, expression was similarly upregulated in kidneys with established fibrosis and low estimated glomerular filtration rates at the time of biopsy. Consistent with a more generic role in kidney fibrosis, in situ hybridization revealed that miR-150-5p was found in lymphoid infiltrates, and areas of proliferation and fibrosis consistent with the known drivers of progression. Thus, miR-150-5p may be a potential functional mediator of kidney fibrosis that may add value in predicting risk of progression in IgA nephropathy and other kidney diseases.

Funding

This work was funded by a grant from Kidney Research UKand the Mayer Family Foundation. JUB was supported by theEuropean Rare Kidney Disease Network (ERKNet) by theDeutsche Forschungsgemeinschaft (BE-3801) and by anintramural grant (Fortune) from the University Hospital ofCologne, Germany.

History

Citation

Kidney International(2021)99(5),1127–1139

Author affiliation

Department of Cardiovascular Sciences

Version

  • VoR (Version of Record)

Published in

Kidney International

Volume

99

Issue

5

Pagination

1127 - 1139

Publisher

Elsevier

issn

0085-2538

eissn

1523-1755

Acceptance date

2020-12-17

Copyright date

2021

Available date

2021-07-06

Spatial coverage

United States

Language

Eng

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