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Abstract Background Furosemide, a commonly used diuretic, activates the renin‐angiotensin‐aldosterone system (RAAS) in other species. Little is known about RAAS peptide activation in horses. Hypothesis/Objectives To evaluate equilibrium analysis as a practical method for RAAS quantification in horses and describe the RAAS response to a single dose of furosemide. We hypothesize that furosemide would cause transient increase in RAAS peptides in horses. Animals 14 healthy adult thoroughbreds from a university teaching herd. Methods Horses received either furosemide (1 mg/kg IV) or saline IV in a crossover study design. Protease‐inhibited samples were compared with equilibrium analysis samples with Deming regression analysis. Renin‐angiotensin‐aldosterone system hormones were evaluated at 0, 0.25, 0.5, 4, and 24 hours postadministration, via equilibrium analysis. Values were compared with a mixed effects model. Results Correlation between protease inhibition and equilibrium analysis was high for angiotensin I peptide (AngI) and angiotensin II peptide (AngII) (r = .92 and .95, respectively). Baseline RAAS peptide concentrations were below the limit of detection except AngII (median, 7.5 [range, 3.5‐14.0] pmol/L). Furosemide administration resulted in an increase in AngI (8.0 [0.5‐15.5] pmol/L, P = .03), AngII (33.7 [9.6‐57.9] pmol/L, P = .0008), angiotensin III peptide (AngIII) (2.9 [0.9‐4.9] pmol/L, P = .0005), angiotensin IV peptide (AngIV) (2.0 [0.6‐3.4] pmol/L, P = .0005), and angiotensin 1‐5 peptide (Ang1‐5) (5.6 [1.2‐5.9] pmol/L, P = .003) at 4 hours. Differences are reported as difference in the mean (95% confidence interval [CI]). Conclusions and Clinical Importance Furosemide produced an increase in hormones associated with both the classical and alternative RAAS pathways. Serum equilibrium analysis is practical for RAAS analysis in horses.

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

Abstract Background The behavior of the comprehensive circulating renin‐angiotensin system (RAS) in dogs with myxomatous mitral valve disease (MMVD) before to the onset of congestive heart failure remains largely unexplored. Hypothesis/Objectives The classical and alternative RAS activity and aldosterone concentrations will be significantly higher in dogs with American College of Veterinary Internal Medicine (ACVIM) stage B2 MMVD compared to normal dogs and dogs with ACVIM stage B1 MMVD. Animals One‐hundred seventeen client‐owned dogs (normal = 60; B1 = 31; B2 = 26). Methods Prospective observational study. Angiotensin peptides (AP) and aldosterone concentrations were measured using liquid chromatography and mass spectrometry. Angiotensin converting enzymes 1 and 2 (ACE, ACE2) and renin activity surrogates were calculated from AP concentrations. Equilibrium dialysis (ED) and immediate protease inhibition (PI) methods of AP quantification were compared in 14 healthy dogs. Results Core RAS activity and aldosterone concentrations did not differ among the 3 groups. However, the balance between the alternative and classical RAS differed, with dogs with stage B2 MMVD having significantly higher ACE2 activity surrogate (ACE2surr) when compared to normal dogs (adjusted P = .02; ratio of medians for ACE2surr [B2:normal], 1.89; 95% confidence interval [CI]: 1.4‐2.6). The ED and PI methods of AP quantification were highly correlated (AngI, r = .9, P

Abstract Background The influence of aldosterone breakthrough (ABT) on proteinuria reduction during renin‐angiotensin system (RAS) inhibition for spontaneous proteinuric chronic kidney disease (CKDP) has not been determined in dogs. Objectives Determine whether ABT occurs in dogs with CKDP and if it is associated with decreased efficacy in proteinuria reduction during RAS inhibitor treatment. Animals Fifty‐six client‐owned dogs with CKDP and 31 healthy client‐owned dogs. Methods Prospective, multicenter, open‐label clinical trial. Dogs were treated with an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker alone or in combination at the attending clinician's discretion and evaluated at 5 time points over 6 months. Healthy dogs were used to determine the urine aldosterone‐to‐creatinine ratio cutoff that defined ABT. The relationship of ABT (present at ≥50% of visits) and proteinuria outcome (≥50% reduction in urine protein‐to‐creatinine ratio from baseline at ≥50% of subsequent visits) was evaluated. Mixed effects logistic regression was used to evaluate the relationship between clinical variables and outcomes (either successful proteinuria reduction or ABT). Results Thirty‐six percent (20/56) of dogs had successful proteinuria reduction. Between 34% and 59% of dogs had ABT, depending on the definition used. Aldosterone breakthrough was not associated with proteinuria outcome. Longer duration in the study was associated with greater likelihood of successful proteinuria reduction (P = .002; odds ratio, 1.6; 95% confidence interval [CI], 1.2‐2.2). Conclusions and Clinical Importance Aldosterone breakthrough was common in dogs receiving RAS inhibitors for CKDp but was not associated with proteinuria outcome.