Gabriella Pathmanathan¹, Chris Neal^2,3, Natalie Finch⁴

¹University of Bristol, Bristol, United Kingdom. ²Wolfson Bioimaging Facility, University of Bristol, Bristol, United Kingdom. ³Bristol Renal, University of Bristol, Bristol, United Kingdom. ⁴Langford Vets, University of Bristol, Bristol, United Kingdom

Objectives

To evaluate glomerular ultrastructural changes associated with acute kidney injury (AKI) in dogs compared with controls.

Methods

Glomerular basement membrane thickness, endothelial fenestration width, density and surface area, proportion of diaphragmed fenestrations and podocyte foot process width, slit width and density were evaluated by transmission electron microscopy in dogs with AKI (n=7) and controls (n=8). Groups were compared using Mann-Whitney U testing and relationships with serum creatinine evaluated with linear regression.

Results

In dogs with AKI (International Renal Interest Society grade I; n=2, VI; n=4, V; n=1), median (range) glomerular endothelial fenestration density and surface area and podocyte slit width were significantly decreased versus controls (0.0029[0.0006-0.0041] vs 0.0039[0.0032-0.0046]/nm P=0.014; 19[5-29] vs 27[22-32]% P=0.021; 28[23-52] vs 42[27-49]nm P=0.040 respectively). Podocyte foot process width was significantly increased (503[309-906] vs 297[239-442]nm P=0.014). Serum creatinine was negatively associated with fenestration density (R²=0.29, P=0.047) and surface area (R²=0.54, P=0.003).

Statement: Impact/ Clinical Significance

Glomerular ultrastructural changes are described in chronic kidney diseases but less established in acute disease. Dogs with AKI demonstrated fenestration loss associated with decreased filtration function, evidence of podocyte foot process effacement and narrowing of podocyte slits. In contrast, changes typically reported in chronic kidney diseases (increased glomerular basement membrane thickness, fenestration width, and diaphragmed fenestrations) were not observed, suggesting these may represent chronic remodeling or reflect limited statistical power. Characterising glomerular ultrastructural changes and their transition in acute and chronic kidney diseases, and their relationship with renal function, may help identify novel therapeutic targets to improve or delay disease progression.