Characterization of the circulating markers of the renin‐angiotensin‐aldosterone system in telmisartan‐ or enalapril‐treated dogs with proteinuric chronic kidney disease

Abstract

Abstract Background Effects of the renin‐angiotensin‐aldosterone system (RAAS) inhibitors enalapril and telmisartan on circulating RAAS in dogs with proteinuric chronic kidney disease (pCKD) are undescribed. Objectives To characterize the RAAS in untreated dogs with pCKD compared to healthy, life‐stage‐ and sex‐matched controls, and in dogs with pCKD after 30 days of treatment with enalapril or telmisartan. Animals Dogs with pCKD (n = 36) and healthy controls (n = 20). Methods Retrospective study of banked samples and previously collected data. Day 0 serum equilibrium concentrations of angiotensin I, II, III, IV, 1‐5, and 1‐7, and aldosterone, and urinary aldosterone‐to‐creatinine ratio (UACR) from pCKD dogs were compared to values on day 30 of treatment with enalapril (0.5 mg/kg PO q12) or telmisartan (1 mg/kg PO q24h) and to those of healthy dogs. Data were analyzed using linear mixed models. Results Compared with healthy dogs, pCKD dogs had significantly higher Ang I, III, 1‐5, and 1‐7 concentrations, and UACR. Relative to pretreatment values, day 30 Ang II concentrations were significantly increased and decreased in telmisartan‐ and enalapril‐treated pCKD dogs, respectively (both P < .001). Mean (95% confidence interval) percentage change from pretreatment value in serum Ang 1‐7 concentration was significantly greater in telmisartan‐ (753% [489%‐1134%]) versus enalapril‐treated (149% [69%‐268%]) dogs (P < .001). Serum aldosterone decreased with treatment (P = .02 for enalapril, P < .001 for telmisartan), with no difference between groups at day 30. Conclusions and Clinical Importance Circulating RAAS activity is higher in dogs with pCKD. Compared with enalapril, treatment with telmisartan caused significantly greater increases in the presumed beneficial peptide Ang 1‐7.

Keywords

• equilibrium analysis
• healthy dogs
• liquid chromatography‐mass spectrometry
• renal proteinuria
• urinary aldosterone‐to‐creatinine ratio