Multiparametric Magnetic Resonance Imaging in a Prospective Cohort of Living Kidney Donors, Recipients, and Healthy Controls and Correlations With Markers of Renal Function, Fibrosis, and Aging (MPRENAL): Protocol for a Longitudinal Observational Study.

The study is designed to validate multiparametric MRI against histological fibrosis from kidney biopsies in kidney transplant recipients and to compare longitudinal trajectories of imaging and functional markers across three cohorts.

• The cohorts are living kidney donors (LKDs), kidney transplant recipients (KTRs), and healthy controls (HCs).
• The planned sample is 32 LKDs, 32 KTRs, and 32 HCs, with up to 40 KTRs recruited to account for attrition.
• Baseline assessments occur before transplantation for LKDs and KTRs and at enrollment for HCs, with follow-up at 3, 12, and 24 months.

The rationale is that current clinical monitoring is insensitive to fibrosis and biopsy is invasive, creating a need for noninvasive imaging biomarkers.

• Renal fibrosis is described as the final common pathway of chronic kidney disease progression and a critical histological predictor of renal function decline and allograft failure.
• Routine monitoring with eGFR and albuminuria is described as insensitive to fibrosis development.
• Renal biopsy is invasive and subject to sampling bias, limiting repeated assessment.
• Individual MRI measures have been associated with fibrosis and declining renal function, but longitudinal validation against histology and measured GFR remains limited.

The mpMRI protocol at 3 T includes multiple structural, quantitative, perfusion, angiographic, and flow sequences.

• Sequences include T1-weighted and T2-weighted imaging, T1 mapping, T2 mapping, T2* mapping, and diffusion-weighted imaging.
• Additional sequences are pseudocontinuous arterial spin labeling, non-contrast enhanced angiography, and phase-contrast measurement of renal artery flow.

Reference standards are measured GFR by [99mTc]Tc-DTPA clearance and stereology-quantified fibrosis in protocol biopsies.

• A baseline allograft biopsy is taken during transplantation surgery.
• Protocol biopsies are taken at 3, 12, and 24 months.
• Fibrosis is quantified using stereology.

The primary outcome is the longitudinal association between corticomedullary T1 difference and histologically determined renal fibrosis in KTRs across all four biopsy time points.

• Linear mixed models will be used to study longitudinal associations.
• Three additional MRI measures will be tested in a fixed sequence to control multiplicity.

Secondary analyses will examine divergence of markers across cohorts, diagnostic performance for fibrosis, and prediction of measured GFR decline.

• Secondary analyses include longitudinal divergence of MRI and functional markers across cohorts.
• Receiver operating characteristic curve analysis will assess diagnostic performance for fibrosis.
• Predictive value for mGFR decline will be assessed in KTRs and LKDs.

Recruitment began in October 2024 and is ongoing, with 42 participants enrolled as of March 2026.

• The study was funded in October 2023; recruitment commenced on October 29, 2024.
• Recruitment is anticipated to close in February 2027, with final study visits by March 2029.
• Primary results are expected to be published in 2030.