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Pharmacodynamic effects of the K+ binder patiromer in a novel chronic hyperkalemia model in spontaneously hypertensive rats.
- Source :
-
Physiological Reports . Sep2020, Vol. 8 Issue 18, p1-11. 11p. - Publication Year :
- 2020
-
Abstract
- Currently described hyperkalemia (HK) animal models are typically acute and cause significant distress and mortality to the animals, warranting new approaches for studying chronic HK in a more appropriate clinical setting. Using the spontaneously hypertensive rat (SHR) model as a more relevant disease template, as well as surgical (unilateral nephrectomy), dietary (3% potassium [K+] supplementation), and pharmacological (amiloride) interventions, we were able to stably induce HK on a chronic basis for up to 12 weeks to serum K+ elevations between 8 and 9 mmol/L, with minimal clinical stress to the animals. Short‐term proof‐of‐concept and long‐term chronic studies in hyperkalemic SHRs showed concomitant increases in serum aldosterone, consistent with the previously reported relationship between serum K+ and aldosterone. Treatment with the K+ binder patiromer demonstrated that the disease model was responsive to pharmacological intervention, with significant abrogation in serum K+, as well as serum aldosterone to levels near baseline, and this was consistent in both short‐term and long‐term 12‐week chronic studies. Our results demonstrate the feasibility of establishing a chronic HK disease state, and this novel HK animal model may be suitable for further evaluating the effects of long‐term, K+‐lowering therapies on effects such as renal fibrosis and end‐organ damage. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 2051817X
- Volume :
- 8
- Issue :
- 18
- Database :
- Academic Search Index
- Journal :
- Physiological Reports
- Publication Type :
- Academic Journal
- Accession number :
- 146139052
- Full Text :
- https://doi.org/10.14814/phy2.14572