MR Elastography in Diabetic Rats: Assessing Glomerular Hyperfiltration, Dapagliflozin Therapy Response, and Early Diabetic Nephropathy

BACKGROUND: Noninvasive detection of glomerular hyperfiltration, a key driver of diabetic nephropathy (DN), is needed for timely intervention (e.g., dapagliflozin), as is early DN identification to guide therapy. PURPOSE: To evaluate MR elastography (MRE) for detecting glomerular hyperfiltration and early DN, using glomerular filtration rate (GFR) and pathology as reference standards. STUDY TYPE: Animal proof of concept. ANIMAL MODEL: Ninety-five male Sprague-Dawley rats (80 with high-fat diet and low-dose streptozotocin-induced type 2 diabetes and 15 normal controls). FIELD STRENGTH/SEQUENCE: ) intravoxel incoherent motion (IVIM) sequence. ASSESSMENT: MRE-derived shear stiffness (SS) and loss modulus (LM) and IVIM-derived true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were measured. Glomerular hyperfiltration and DN classes were diagnosed by direct GFR measurement and renal pathology. Ex vivo rheometry validated MRE-derived viscoelastic parameters. STATISTICAL TESTS: Linear mixed-effects models; one-way analysis of variance (ANOVA) or Welch's ANOVA; Pearson correlation; intraclass correlation coefficient (ICC); area under the receiver operating characteristic curve (AUC) and DeLong's test. p < 0.05 was considered significant. RESULTS: Renal SS was significantly higher in hyperfiltration than in controls and early DN (class I-II), distinguishing hyperfiltration from controls (AUC = 0.94) and from early DN (AUC = 0.90). LM was elevated in hyperfiltration but did not decrease significantly in early DN (p > 0.99 vs. hyperfiltration). IVIM parameters showed limited diagnostic utility (AUCs: 0.53-0.72). Dapagliflozin treatment normalized the elevated SS and LM in diabetic rats. Ex vivo rheometry showed significant positive correlations with MRE-derived SS and LM. DATA CONCLUSION: Three-dimensional MRE-derived renal SS is a potential noninvasive biomarker to detect diabetic glomerular hyperfiltration, monitor response to dapagliflozin therapy, and enable early identification of DN. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.