Abstract: FR-PO0642
Combined Tolvaptan and Renal Denervation in a Rat Model of Autosomal Recessive Polycystic Kidney Disease (ARPKD)
Session Information
- Cystic Kidney Diseases: Basic and Translational Research
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Banek, Christopher T, University of Minnesota Medical School, Minneapolis, Minnesota, United States
- Encinas, Noah, The University of Arizona College of Medicine Tucson, Tucson, Arizona, United States
- Zozobrado, Lizetta T, The University of Arizona College of Medicine Tucson, Tucson, Arizona, United States
- Foster, Thaiane, The University of Arizona College of Medicine Tucson, Tucson, Arizona, United States
- Nilsson, Arielle K, The University of Arizona College of Medicine Tucson, Tucson, Arizona, United States
- Hayoz, Sebastien, University of Minnesota Medical School, Minneapolis, Minnesota, United States
- Van Helden, Dusty, University of Minnesota Medical School, Minneapolis, Minnesota, United States
Background
ARPKD is a rare genetic disease marked by early, rapid renal cystogenesis and progression to renal failure, and treatments remain limited. Tolvaptan (TV), a vasopressin receptor 2 antagonist, slows cyst growth in the PCK rat model of ARPKD but is not used clinically for ARPKD. Our lab reported a similar cyst-reducing effect with renal denervation (RDNx). We aimed to assess the separate and combined effects of TV and RDNx in PCK rats, and we hypothesized that both reduce cyst growth, with enhanced effects when combined.
Methods
PCK rats (n=48; Age: 4 weeks) were randomized into four groups: Sham+Vehicle, Sham+TV, RDNx+Vehicle, and RDNx+TV (n=12/group; 6M/6F). Surgeries (sham or RDNx) were performed at week 4. TV was given in chow (0.1% w/w) through week 10. RDNx was achieved by bilateral renal nerve dissection and 10% phenol; sham applied saline. Renal function was assessed by serum creatinine, BUN, and 24Hr urine. Kidneys were collected for histological analysis at week 10. Renal cystic index (% cyst area) was determined histologically. Data presented as mean±SEM and analyzed by two-way ANOVA with Dunnett’s post hoc (*p<.05 vs. Sham+Vehicle)
Results
In males, cystic index was similarly reduced across RDNx, TV, and RDNx+TV vs. Sham+Vehicle (*7.3±1.1 vs. *5.4±0.8 vs. *7.0±0.9 vs. 11.7±1.2%). No treatment effect was observed in females. TV and RDNx+TV increased 24-hour urine output and water intake (see Table) in males, with greater effect in females. RDNx alone had no polyuric effect in either sex. Serum creatinine and BUN were unaffected by treatment or sex.
Conclusion
These findings partially support our hypothesis. RDNx and TV both reduced cyst growth in males, but no additive effect was detected with RDNx+TV. No treatment effect was detected on cystic index in females. To our knowledge, we are the first to report sex-specific differences in polyuria and anti-cystic responses to TV in PCK rats. Importantly, RDNx matched TV efficacy in males without polyuric effects. The absence of additive benefit suggests a shared mechanism, and current studies are testing these treatments in an aged PCK cohort (6-months).
24H Urine (mL/kg)
| Sham+Chow | TV+Chow | RDNx+Chow | RDNx+TV | |
| Male | 37.9±5.3 | *41.9±3.8 | 31.3±5.7 | *73.3±9.7 |
| Female | 53.4±9.4 | *162.6±24.7 | 35.6±4.7 | *124.6±9.0 |
Funding
- NIDDK Support