Effect of calcifediol supplementation on renin-angiotensin-aldosterone system mediators in dogs with chronic kidney disease

J Vet Intern Med. 2022 Sep;36(5):1693-1699. doi: 10.1111/jvim.16499. Epub 2022 Aug 13.

Abstract

Background: Chronic kidney disease (CKD) leads to low serum concentrations of vitamin D metabolites. Thus, hypovitaminosis D associated with CKD might contribute to disease progression via increased concentration of renin angiotensin aldosterone system (RAAS) mediators.

Objectives: To evaluate whether supplementation with calcifediol affects equilibrium concentrations of selected mediators of the RAAS. We hypothesized that vitamin D supplementation will decrease concentration of circulating RAAS mediators in dogs with CKD.

Animals: Six client-owned adult dogs with IRIS Stage 2 and 3 CKD.

Methods: Prospective study. Serum 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2 D), 24,25-dihydroxyvitamin D (24,25[OH]2 D), RAAS mediators (angiotensin I/II/III/IV/1-5/1-7, and aldosterone), and surrogate angiotensin converting enzyme (ACE) activity (calculated by the ratio of angiotensin II to angiotensin I) were evaluated at baseline, after 3 months of calcifediol supplementation, and 2 months after discontinuing administration of supplement.

Results: All serum vitamin D metabolite concentrations increased significantly by month 3 (P < .001): 25(OH)D (median 250 ng/mL; range, 204-310), compared to baseline (median 43.2 ng/mL; range, 33.8-58.3 ng/mL); 1,25(OH)2 D (median 66.1 pg/mL; range, 57.3-88.1 pg/mL) compared to baseline (median 35.2 pg/mL; range, 29.3-56.7 pg/mL); 24,25(OH)2 D (median 68.4 ng/mL; range, 22.1-142.0 ng/mL) compared to baseline (median 14.4 ng/mL; range, 9.0-21.3 ng/mL). Calculated ACE activity was significantly lower at month 3 (median 0.5; range, 0.4-1.0) compared to baseline (median 0.7; range, 0.6-1.3; P = .01). There were no significant differences in any of the evaluated RAAS variables at any other time-point.

Conclusions and clinical importance: Short-term calcifediol supplementation in this small group of CKD dogs appeared to decrease ACE activity.

Keywords: aldosterone; angiotensin; renin; vitamin D.

MeSH terms

  • Aldosterone
  • Angiotensin I / pharmacology
  • Angiotensin II
  • Animals
  • Calcifediol / pharmacology
  • Dietary Supplements
  • Dog Diseases* / drug therapy
  • Dogs
  • Peptidyl-Dipeptidase A
  • Prospective Studies
  • Renal Insufficiency, Chronic* / drug therapy
  • Renal Insufficiency, Chronic* / veterinary
  • Renin-Angiotensin System
  • Vitamin D

Substances

  • Angiotensin II
  • Vitamin D
  • Aldosterone
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • Calcifediol

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