A new intrasurgical technique to safely and reproducibly induce partial unilateral urinary obstruction and renal scarring in a Rat Model

Objective Irreversible electroporation (IRE) uses microsecond-long electric pulses to kill cells through membrane permeabilization, without affecting surrounding extracellular structures. We evaluated whether IRE can be used to induce urinary obstruction for a rat model of renal scarring. Materials and methods Intrasurgical IRE (2000 V/cm, 90 pulses, 100 μs) with caliper electrodes was performed in the right proximal ureter in male rats ( n = 24) which were euthanized at 2, 5, or 10 days post-treatment, following contrast-enhanced magnetic resonance imaging. Complete urinary tract (bilateral kidneys, ureter and bladder) was extracted, and scored on a five-point scale for renal dilation, ureteral dilation and hydronephrosis. Whole kidney sections underwent immunohistochemistry to quantify levels of macrophages (CD68), activated fibroblasts [α-smooth muscle actin (α-SMA)], collagen (Masson’s Trichrome) and Hematoxylin and Eosin. Change in renal pelvis diameter and the number of glomeruli in the treated and contralateral urinary tract was also computed. Results Intrasurgical IRE performed with non-invasive caliper electrodes resulted in immediate loss of peristalsis in the treated ureteral segment, and cell death in the ureteral muscularis along with urothelial sloughing. Dilation of the ureter was observed on gross anatomic evaluation and histopathology. Magnetic resonance imaging indicated partial stricture and urinary obstruction in IRE-treated urinary tract, without evidence of urinoma, leakage or fistula formation. Enlargement of the kidney with progressive renal dilation and hydronephrosis was evident between Day 2 and Day 10 post-treatment. Obstructed kidney demonstrated scarring with elevated levels of tissue collagen, macrophages and α-SMA-positive fibroblasts. There was a steady decrease in the number of glomeruli in the obstructed kidney, while glomeruli numbers in the contralateral kidney remained unchanged through the 10-day observation period. Conclusion IRE provides a safe and reproducible technique to induce partial ureteral obstruction and renal fibrosis in rat model without the need for ligation or its associated complications.