Effect of the sampling time on urinary electrolytes following furosemide administration in dogs with myxomatous mitral valve disease

Furosemide is the first-choice treatment for congestive heart failure in dogs with myxomatous mitral valve disease (MMVD). Urinary electrolytes have received growing attention to estimate diuretic response in both human and veterinary medicine. The aim of the study was to evaluate the impact of time elapsed between oral furosemide administration and sample collection on urine electrolyte concentrations in dogs with MMVD American College of Veterinary Internal Medicine (ACVIM) stage C. Dogs with stable MMVD ACVIM C receiving oral furosemide twice daily (median daily dose 4 mg/kg), were prospectively enrolled in the study. Other standard cardiovascular treatments were allowed.Healthy untreated dogs (n=106) were included for comparison. MMVD dogs were grouped based on the time elapsed between furosemide administration and samples collection: MMVD Morning Group(MMVD-MG) from 1 to 6 hours; MMVD Evening Group (MMVD-EG)> 6 hours. Analogously, healthy dogs were divided in two groups according to the time of blood/urine sampling: Healthy-MorningGroup (H-MG) between 9 a.m. and 1 p.m.; Healthy-Evening Group (H-EG) between 2 and 7 p.m. Laboratory variables including serum and urine electrolytes and fractional excretion (FE) of electrolytes were measured. Data were reported as median and minimum-maximum values and compared with non parametric statistics (P<0.05 considered significant). Seventy-three dogs with MMVD ACVIM C were included. No significant difference was observed between MMVD-MG and MMVD-EG for serum creatinine, urea and serum electrolytes. If compared to theMMVD-EG, MMVD-MG group had significantly higher urine sodium (71.1, 5.9-192.9 vs. 36.3, 4.6-103.9; p=0.021), urine sodium to creatinine ratio (uNa:uCr; 1.63, 0.09-118.22 vs. 0.50, 0.06-2.82; p=0.003), FE of sodium (FENa; 1.3, 0.08-10.7 vs. 0.45, 0.06-2.5; p=0.008), urinechloride (68.2, 6-148.1 vs. 32.5, 5-114.8; p=0.038), urine chloride to creatinine ratio (uCl:uCr; 1.51, 0.09-14.7 vs. 0.44, 0.06-2.99;p=0.008), FE of chloride (FECl; 1.54, 0.08-14.8 vs. 0.53, 0.07-4;p=0.015) and urine sodium to urine potassium ratio (uNa:uK; 1.67,0.11-10.21 vs. 0.93, 0.14-3.77; p=0.016). No significant difference was found between H-MG and H-EG. The MMVD-MG group had significantly higher FENa, FECl and uNa:uK compared to H-MG (p<0.0001, p=0.0004 and p=0.0001, respectively). No difference was detected between MMVD-EG and H-EG. In conclusion, time of sampling should be standardized when evaluating urine chemistry in dogs with MMVD receiving furosemide. Blood and urine sampling at <6 hours from oral furosemide administration should be recommended in the clinical practice.