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

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.

To evaluate MR elastography (MRE) for detecting glomerular hyperfiltration and early DN, using glomerular filtration rate (GFR) and pathology as reference standards.

Animal proof of concept.

Ninety-five male Sprague-Dawley rats (80 with high-fat diet and low-dose streptozotocin-induced type 2 diabetes and 15 normal controls).

Briefly, 3.0 T; a multifrequency (100, 150, and 200 Hz) three-dimensional MRE sequence and a multi-b-value (0-800 s/mm²) intravoxel incoherent motion (IVIM) sequence.

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.

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.

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.

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.

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Stage 2.