Non-Invasive Magnetic resonance imaging Biomarkers to evaLuatE histology-proven kidney fibrosis in Chronic Kidney Disease (NIMBLE-CKD): an observational cohort study protocol
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Introduction
Chronic kidney disease (CKD) affects 1 in 10 people worldwide and can progress towards kidney failure, which is best predicted by the severity of kidney fibrosis. Currently, kidney fibrosis can only be detected by invasive kidney biopsy which carries procedural risks with limitations on repeat testing. Magnetic resonance imaging (MRI) techniques have emerged as potential surrogate markers for kidney fibrosis, though data remains limited. To date, no studies have examined post-gadolinium contrast T1-mapping in kidney fibrosis despite its proven utility in assessing myocardial fibrosis. This study aims to develop a multiparametric MRI biomarker including post-contrast imaging to quantify kidney fibrosis in individuals with CKD.
Methods and analysis
In this observational cohort study, a control group of 20 healthy adult volunteers will establish healthy kidney MRI parameters. Two adult non-dialysis CKD cohorts (each n=24) who have undergone kidney biopsy within the last month will derive and validate the MRI models, respectively. Tubulointerstitial fibrosis on kidney biopsy will be assessed by Masson trichome staining and quantified based on the percentage of cortex affected by blinded pathologists. All participants will undergo a single multiparametric kidney MRI including kidney volumetry, T1- (pre- and post-low-dose contrast), T2- and T2*-mapping, diffusion weighted imaging and phase-contrast MRI of renal artery flow. The primary outcome will be the association between a composite multiparametric MRI marker and tubulointerstitial fibrosis with a minimum variance of 50%. The association between the multiparametric MRI marker and individual MRI variables, and tubulointerstitial fibrosis, estimated glomerular filtration rate and albuminuria will also be studied.
Ethics and dissemination
Ethics approval has been obtained by the Northern Sydney Local Health District Human Research Ethics Committee (2022/ETH00972). Results will be disseminated in relevant peer-reviewed journals and presented at academic conferences.
Registration details
This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000855729p).
STRENGTHS AND LIMITATIONS OF THIS STUDY
Kidney magnetic resonance imaging (MRI) is a growing area of interest due to its potential to provide a comprehensive assessment of kidney microstructure, haemodynamic properties, and function.
This study combines emerging and novel MRI techniques to develop a non-invasive biomarker for kidney fibrosis which can currently only be quantified histologically by kidney biopsy.
The multiparametric MRI models utilised in this study facilitates the examination of multiple MRI techniques including volumetry, T1-,T2-, and T2*-mapping, diffusion weighted imaging, and phase-contrast MRI in a single examination.
To our knowledge, this is the first study to examine post-contrast T1-mapping in kidney MRI in the detection of kidney fibrosis.
Limitations of this study include its limited sample size and lack of prospective follow-up, thus restricting its ability to report on the prognostic value of the proposed MRI biomarker.
