Clinical utility of BOLD-MRI in accurate diagnosis and prognostic evaluation of diabetic nephropathy: a prospective renal biopsy-based cohort study

Abstract

Objectives: To validate blood oxygen level-dependent MRI (BOLD-MRI) for non-invasive discrimination of diabetic nephropathy (DN) vs non-diabetic renal disease (NDRD) and prediction of end-stage renal disease (ESRD) in diabetic kidney disease (DKD).

Materials and methods: A prospective cohort of 133 biopsy-proven DKD patients underwent BOLD-MRI. The semi-automated 12-layer concentric-objects method was used to analyze BOLD-MRI variables. Prognostic markers for ESRD were identified using univariate and multivariate Cox regression. Feature importance was used to select key diagnostic variables and establish logistic regression and machine-learning differential diagnosis models.

Results: Among 133 patients (44 DN, 55 NDRD, 34 combined), 20 (15.5%) progressed to ESRD over a mean of 21.8 months. Higher renal medullary R2* (MR2*) (> 24 1/s) reduced ESRD risk by 52% (HR, 0.48) in DKD. Prognostic models integrating pathological grouping, hemoglobin levels, and cysC levels achieved a c-index of 0.90. For the DN and combined groups, MR2*, glomerular grading, interstitial lesions, interstitial fibrosis, and tubular atrophy were predictive of ESRD, with a c-index of 0.91. For differential diagnosis, the random forest (RF) model achieved an AUC of 0.901, with diabetic retinopathy, diabetes duration, albumin, blood urea nitrogen, MR2*, hypertension, and glycosylated hemoglobin as the most contributing factors. For the combined group classified as DN, the AUC of the RF model was 0.791; when classified as NDRD, the AUC was 0.856.

Conclusion: MR2* shows potential value as a non-invasive diagnostic and prognostic tool in the assessment of DKD. However, BOLD-MRI remains a promising yet exploratory technique that requires external validation and interventional studies before clinical implementation.

Critical relevance statement: Blood oxygen level-dependent-MRI-derived renal medullary R2* robustly predicts ESRD risk and distinguishes DN without biopsy, offering an immediately translatable, non-invasive biomarker for the precision management of DKD in routine nephrology practice.

Trial registration: ClinicalTrials.gov, NCT03865914.

Key points: Blood oxygen level-dependent-MRI medullary R2*(MR2*) > 24 s^-1 halves DKD ESRD risk (HR 0.48). MR2* integrated with clinical variables drives c-index to 0.90 for ESRD prognosis. RF leveraging MR2* and clinical traits attains an AUC of 0.901 for diagnosing DN.

Keywords: BOLD-MRI; Diabetic nephropathy; Differential diagnosis; Prognostic marker; R2*.