JMIR Publications

ABSTRACT

Background:

Renal fibrosis is the final common pathway of chronic kidney disease progression and a critical histological predictor of renal function decline and allograft failure. Routine clinical monitoring with estimated glomerular filtration rate (eGFR) and albuminuria is insensitive to the development of fibrosis. Renal biopsy is invasive, which limits repeated assessment and suffers from sampling bias. Consequently, non-invasive imaging biomarkers that can accurately quantify fibrosis, monitor disease progression, and predict outcomes are highly desirable. Multiparametric magnetic resonance imaging (mpMRI) offers extensive characterization of renal structural and functional properties. Previous work has indicated that MRI measures are associated with fibrosis development and with declining renal function. However, there remains a sparsity of longitudinal data and comprehensive validation of MRI measures against histology and measured glomerular filtration rate (mGFR).

Objective:

Our ongoing longitudinal study aims to validate mpMRI against reference standard kidney biopsy in kidney transplant recipients (KTR) and to compare the time-dependent trajectories of imaging and functional markers across living kidney donors (LKD), KTR and healthy control (HC) cohorts to assess their prognostic value for mGFR decline.

Methods:

Participants: 32 living kidney donors (LKD), 32 KTR, and 32 healthy controls (HC). Inclusion criteria: LKD and KTR who have been approved for transplant. HC must show no evidence of renal disease and have normal blood pressure. Exclusion criteria: Contraindications to MRI or severe claustrophobia. Time points: Baseline investigations prior to transplant surgery, with follow-up assessments at 3-, 12-, and 24-months post-transplant. Data collection: mpMRI is performed at 3T. The MRI protocol includes structural T1-weighted and T2-weighted imaging, T1 mapping, T2 mapping, T2* mapping, DWI, pseudo-continuous ASL, non-contrast-enhanced angiography, and phase-contrast measurement of renal artery flow. Glomerular filtration rate will be measured by [99mTc]Tc-DTPA clearance. A baseline allograft biopsy is performed in all KTR during the transplantation surgery. Subsequent protocol biopsies are planned at 3, 12, and 24 months in KTR. Extent of fibrosis is quantified using quantitative stereology. Primary outcome: Longitudinal association between quantitative MRI measures and histologically determined renal fibrosis. Secondary outcomes: Longitudinal divergence of MRI and functional markers across cohorts; diagnostic performance for fibrosis; and predictive value for mGFR decline in KTR and LKD. Linear mixed models will be used to study longitudinal associations. Receiver operating characteristic curve analysis will assess diagnostic performance.

Results:

Recruitment for the MPRENAL study commenced in November 2024. As of March 2026, enrolment is ongoing with 42 participants recruited. Full data analysis and results are projected for December 2029.

Conclusions:

Successful completion of this study is expected to provide robust histological validation of mpMRI and establish its utility as a non-invasive tool for monitoring renal health. Clinical Trial: ClinicalTrials.gov NCT06210555; https://clinicaltrials.gov/ct2/show/NCT06210555