EN01 - Characterization of the Renin-angiotensin-aldosterone System in Telmisartan- or Enalapril-treated Dogs with Proteinuric Chronic Kidney Disease

Abstract: Background: The relative effects of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on the circulating renin-angiotensin-aldosterone system (RAAS) in dogs with proteinuric chronic kidney disease (CKD) are undescribed.

Objective: To characterize the RAAS in dogs with CKD treated with an ACEi (enalapril) or ARB (telmisartan).

Samples: Serum and urine from dogs with naturally occurring proteinuric CKD (n=36).

Methods: Serum concentrations of angiotensin (Ang) peptides (Ang I, II, III, IV, 1-5, and 1-7) and aldosterone, and urinary aldosterone-to-creatinine ratio (UACR) were determined using samples collected prior to and after 30 days of treatment with enalapril (n=17) or telmisartan (n=19). Liquid chromatography and mass spectrometry were used to determine serum concentrations of Ang peptides and aldosterone. Data were analyzed using linear mixed models controlling for concurrent treatment with amlodipine, presence of heart disease, and age.

Results: Relative to pre-treatment values, serum concentrations of Ang II were significantly increased and decreased in telmisartan- and enalapril-treated dogs, respectively (both P < 0.001). Mean [95% CI] percentage change from pre-treatment value in serum Ang1-7 concentration was significantly greater in telmisartan- (753% [489% to 1134%]) versus enalapril-treated (149% [69% to 268%]) dogs (P < 0.001). Differences in percentage change in serum aldosterone or UACR, and significant effects of concurrent amlodipine treatment, presence of heart disease, or age, were not observed.

Conclusions and clinical importance: Compared to enalapril, treatment with telmisartan was associated with significantly greater increases in the beneficial Ang peptide Ang1-7, representing a potential treatment advantage of the latter in dogs with CKD.