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논문분류	춘계학술대회 초록집
제목	Retrograde Ureteral Dosing in Nonhuman Primates for Drug Delivery to the Kidney
저자	Aldric Hama
출판정보	2026; 2026(1):
키워드	preclinical, cynomolgus macaca, renal dosing
초록	Objectives: For non-clinical testing, new renal disease treatment efficacy evaluation is hampered since these are usually systemically administered. A noninvasive method was developed to deliver treatments for preclinical evaluation to the kidneys in cynomolgus macaques. Methods: Under general anesthesia, a veterinary endoscope (Karl Storz, Germany) was introduced via the urethra into the bladder, allowing visualization of the ureteral orifices of female cynomolgus macaques. A guidewire was then inserted into the ureteral orifice, followed by the advancement of a balloon catheter along the wire. The catheter tip was positioned near the renal pelvis, and its location was confirmed using a C-arm fluoroscope (GE, US). Iohexol contrast agent or about 1 ml of polystyrene fluorescent microspheres (diameter 25 nm, Lab261, USA) was injected through the catheter into the renal pelvis. Twenty-four to forty-eight hours after dosing of microspheres, kidneys were harvested to determine microsphere distribution. Results: Fluoroscopic imaging confirmed positioning of the catheter tip near the renal pelvis. Fluorescent microspheres were found in the ipsilateral renal tubule epithelial cells and not in other cell types. Some microspheres were apparently observed in tubule cells in the contralateral un-injected kidney. Retro-ureter catheter insertion was achieved without complications in three macaques. The procedure was well tolerated in all subjects, with no significant bleeding during the procedure and no postoperative hemorrhage or health abnormalities observed. Conclusion: Clinically utilized retrograde-ureter dosing, direct delivery of therapeutics to the kidney, was successfully scaled down for preclinical use in the cynomolgus macaque for safety and efficacy testing. This preclinical method enables drug administration directly to the kidney in contrast to standard dosing via a systemic route, with distribution, using microspheres, apparently limited to the kidneys.
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