Abstract: FR-PO264
Ouabain Treatment Increases Cyst Progression in a Slowly Progressive Autosomal Dominant Polycystic Kidney Disease Mouse Model
Session Information
- Genetic Diseases of the Kidneys: Cystic - II
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1101 Genetic Diseases of the Kidneys: Cystic
Authors
- Trant, Jordan, The University of Kansas Medical Center, Kansas City, Kansas, United States
- De Blanco, Gladis Sanchez, The University of Kansas Medical Center, Kansas City, Kansas, United States
- Mcdermott, Jeff P., The University of Kansas Medical Center, Kansas City, Kansas, United States
- Blanco, Gustavo, The University of Kansas Medical Center, Kansas City, Kansas, United States
Background
Renal cyst progression in Autosomal Dominant Polycystic Kidney Disease (ADPKD) is highly dependent on agents circulating in blood. We have previously shown that one of these agents is the hormone ouabain. By binding to its cell surface receptor Na,K-ATPase (NKA), ouabain triggers a cascade of signal transduction events in the cells, which enhances ADPKD cystogenesis via two main mechanisms: increased cell proliferation and enhanced fluid secretion of the cystic renal tubular epithelial cells. These effects were obtained using in vitro models of ADPKD. Here, we determined the effects of ouabain in vivo using an ADPKD mouse model.
Methods
Ouabain (0.3 mg/g) or saline was injected intraperitoneally to wildtype (WT) mice and a slowly progressive ADPKD model (RC/RC mice). Ouabain was administered daily, starting at postnatal day 9 and for 1-5 months. Kidney weight to body weight ratio (KW/BW), blood urea nitrogen (BUN), percent of cystic area (% cyst area), and kidney fibrosis were then measured.
Results
Ouabain treatment significantly increased the % cyst area in RC/RC mice compared to saline-injected controls at all time points. The KW/BW was also augmented in RC/RC mice at 3, 4, and 5 months of treatment. There were no differences observed between male and female mice, and these effects were not seen in WT mice. BUN values were not affected by ouabain in either of the groups tested. Between 1 and 5 months, ouabain significantly increased fibrosis in the RC/RC mice compared with the saline-injected controls.
Conclusion
These findings demonstrate that ouabain stimulates kidney cyst progression in ADPKD not only in vitro, but also in vivo. Since the dose of ouabain that we used is within the reported normal physiological range, our results support the idea that circulating levels of this hormone could be contributing to cyst progression in ADPKD patients.
Funding
- NIDDK Support