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

J Vet Intern Med. 2024 Sep-Oct;38(5):2535-2547. doi: 10.1111/jvim.17186. Epub 2024 Aug 29.

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.

MeSH terms

  • Aldosterone* / blood
  • Angiotensin-Converting Enzyme Inhibitors* / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors* / therapeutic use
  • Angiotensins / blood
  • Animals
  • Biomarkers / blood
  • Case-Control Studies
  • Creatinine / blood
  • Dog Diseases* / blood
  • Dog Diseases* / drug therapy
  • Dogs
  • Enalapril* / pharmacology
  • Enalapril* / therapeutic use
  • Female
  • Male
  • Proteinuria / drug therapy
  • Proteinuria / veterinary
  • Renal Insufficiency, Chronic* / blood
  • Renal Insufficiency, Chronic* / drug therapy
  • Renal Insufficiency, Chronic* / veterinary
  • Renin-Angiotensin System* / drug effects
  • Retrospective Studies
  • Telmisartan* / pharmacology
  • Telmisartan* / therapeutic use

Substances

  • Telmisartan
  • Enalapril
  • Angiotensin-Converting Enzyme Inhibitors
  • Aldosterone
  • Biomarkers
  • Creatinine
  • Angiotensins