Role of electrolyte concentrations and renin‐angiotensin‐aldosterone activation in the staging of canine heart disease

Abstract

Background: Refractory congestive heart failure (CHF) and associated diuretic resistance are not well defined.Objectives: To characterize renal function, electrolyte concentrations, indices of diuretic efficacy, and renin-angiotensin-aldosterone system (RAAS) activation in dogs with naturally occurring heart disease (HD) in American College of Veterinary Internal Medicine stages B1, B2, C, and D and to determine their usefulness in defining HD stages.Animals: Group 1:149 dogs with HD stages B1, B2, C, and D. Group 2:22 dogs with HD stages C and D.Methods: Group 1: Renal parameters, serum and urine electrolyte and diuretic concentrations, and urine aldosterone concentrations were measured. Medication dosages and measured variables were compared among stages. Correlation of furosemide dosages to serum concentrations was explored. Group 2: Angiotensin-converting enzyme activity and RAAS components were measured and compared among CHF stages.Results: Serum chloride concentration was the best differentiator of HD stage. Furosemide PO dosages (≤6 mg/kg/day) were weakly correlated with serum furosemide concentrations, whereas higher dosages were not significantly correlated.Angiotensin-converting enzyme inhibitor dosage and RAAS inhibition were greater in stage D, compared to stage C dogs.Conclusions and Clinical Importance: Hypochloremia is a useful marker for stage D HD in dogs. Poor furosemide dosage correlation to serum concentration may indicate variable and poor absorption, especially at higher dosages, advanced disease, or both.A small number of stage D dogs met proposed criteria for diuretic resistance. Greater RAAS inhibition in stage D versus stage C indicates effectiveness of RAASsuppressive treatments in this group of dogs with refractory CHF.

Factors affecting the urinary aldosterone-to-creatinine ratio in healthy dogs and dogs with naturally occurring myxomatous mitral valve disease

“…Urinary aldosterone-to-creatinine ratio was not significantly different among healthy and MMVD dogs of different stages, similarly to what reported by two recent studies [ 17 , 34 ]. Several factors may have influenced this result.…”

“…Stage C dogs were expected to show an overstimulation of RAAS compared to healthy and pre-clinical MMVD dogs [ 2 , 24 ], but the complexity of therapy and its influence on RAAS make difficult to interpret the result. All stage C dogs were receiving drugs with opposite effects on RAAS (ACEI vs diuretic) [ 1 , 17 , 41 – 44 ] and 20 dogs were also treated with spironolactone, which prevents aldosterone’s binding to mineralcorticoid receptor, leading to an increase in blood and urine aldosterone concentrations [ 3 , 34 , 38 , 45 ]. As expected, dose of furosemide was positively associated with UAldo:C in the regression analysis and stage C dogs receiving spironolactone showed a significantly higher UAldo:C than those not treated.…”

Prediction and measurement of diuretic responsiveness after oral administration of furosemide to healthy dogs and dogs with congestive heart failure

“…AUC, area under the curve versus uVol: r = 0.976, P < .001) highlighting the close relationship between Na and uVol, under what might be considered optimal conditions. 17 In our study, the correlation between cumulative uNa output and uVol was comparatively less (r = 0.643) and highlighted how uNa and uVol can become disconnected, particularly in dogs with CHF. In dogs, specific criteria for LDR are lacking, and further study is warranted.…”

“…9 Between 6 and 25% of dogs with severe chronic CHF had LDR according to various criteria adapted from human medicine. 17 Measuring diuretic responsiveness is challenging. Cumulative uVol and uNa output over multiple hours after diuretic dosing have been assiduously collected and measured in humans [18][19][20][21] and experimental dogs 13,14 but is not practicable in most clinical settings.…”

Correction of serum chloride concentration in dogs with congestive heart failure

“…Low serum [Cl − ] (<103.5 mmol/L) is a sensitive and specific differentiator of refractory (American College of Veterinary Medicine [ACVIM] Stage D) congestive heart failure (CHF) from controlled (ACVIM Stage C) CHF in dogs 14 . Additionally, hypochloremia is associated with presumed diuretic resistance in dogs and people with refractory CHF, and may contribute to cardiorenal syndrome 14‐17 . Unbalanced loop diuretic‐induced electrolyte depletion (as a result of urinary chloride loss twice that of sodium when the Na + /K + /2Cl − cotransporter in the ascending loop of Henle is inhibited) and nonosmotic ADH release causing electrolyte dilution are both potential contributors to CHF‐associated hypochloremia and hyponatremia 14,18 .…”