Fibroblast growth factor-23 as an early marker of CKD-mineral bone disorder in dogs: preliminary investigation.

OBJECTIVES: To examine the relationship between fibroblast growth factor-23 levels, chronic kidney disease severity and mineral metabolic disorders associated to chronic kidney disease in dogs. MATERIALS AND METHODS: Fifteen control and 75 chronic kidney disease dogs were retrospectively included. Serum fibroblast growth factor-23 concentration and other phosphate metabolite parameters were compared between controls and each International Renal Interest Society stage. Multiple regression analysis was performed to determine the predictors of fibroblast growth factor-23. RESULTS: Serum fibroblast growth factor-23 concentrations were significantly higher in dogs with IRIS stages 2, 3 and 4 chronic kidney disease than those in dogs in control group and with stage 1 and increased along with the severity of chronic kidney disease. Compared with control dogs, serum intact parathyroid hormone significantly increased from stage 2 and serum phosphorus concentrations increased in dogs with stage 4. In dogs with stage 2, fibroblast growth factor-23 levels significantly increased in those with hyperphosphatemia compared with those with normophosphatemia. While eight of 26 (30.8%) dogs with stage 2 developed hyperparathyroidism (intact parathyroid hormone>8.5 ng/L), 19 (73.1%) dogs with stage 2 had elevated fibroblast growth factor-23 levels above the reference range (>528 pg/mL). Log creatinine, log intact parathyroid hormone and log product of total calcium and phosphorus were independent predictors of log fibroblast growth factor-23. CLINICAL SIGNIFICANCE: This preliminary study suggests that canine fibroblast growth factor-23 might be involved in mineral metabolic disorders associated to chronic kidney disease in dogs, and this factor could be potentially used as an early marker for this condition.

Use of vertebral left atrial size for staging of dogs with myxomatous valve disease.

INTRODUCTION/OBJECTIVES: The American College of Veterinary Internal Medicine (ACVIM) guidelines suggest that pimobendan should be initiated in dogs which meet all criteria of stage B2 myxomatous mitral valve disease (MMVD): murmur intensity ≥ 3/6, left atrial-to-aortic ratio ≥ 1.6, normalized left ventricular internal diameter in diastole ≥ 1.7, and vertebral heart size > 10.5. Recently, a new radiographic index for left atrial enlargement, vertebral left atrial size (VLAS), was proposed. The objective of the present study was to evaluate whether VLAS is useful in staging MMVD and if it can distinguish between ACVIM stages B1 and B2. ANIMALS: Ninety-seven client-owned dogs with MMVD were evaluated and classified as ACVIM stage B1, B2, or C-D. MATERIALS AND METHODS: The echocardiographs and radiographs of all the dogs were retrospectively evaluated to obtain left atrial-to-aortic ratio, normalized left ventricular internal diameter in diastole, and VLAS values. The data were analyzed to assess the correlation between these measurements and VLAS, and the optimal cutoff value of VLAS was determined. RESULTS: A VLAS cutoff value of 2.6 provided the greatest diagnostic accuracy for identification of dogs with ACVIM stage B2 MMVD (area under the curve, 0.96; sensitivity, 95%; specificity, 84%). A VLAS ≥2.5 exhibited the highest sensitivity (sensitivity, 100%; specificity, 78%), and a VLAS ≥ 3.1 exhibited the highest specificity (sensitivity, 47%; specificity, 100%). CONCLUSIONS: VLAS is a helpful index for monitoring MMVD using radiography. A VLAS cutoff value of 2.5 could be used to identify dogs that may benefit from echocardiography to determine if they have reached ACVIM stage B2.

Evaluation of the inhibitory effects of telmisartan on drug-induced renin-angiotensin-aldosterone system activation in normal dogs.

INTRODUCTION: This study examined whether the angiotensin II receptor blocker telmisartan had inhibitory effects on drug-induced renin-angiotensin-aldosterone system (RAAS) activation in normal dogs. ANIMALS: Five healthy laboratory beagles were used in this study. METHODS: Each dog received amlodipine (0.5 mg/kg, q12h, PO) alone for 14 days. Starting on the next day, animals received both amlodipine and telmisartan (1.0 mg/kg, q24h, PO) for 84 days. Systolic blood pressure, heart rate, plasma biochemical variables (blood urea nitrogen, creatinine, and electrolytes), plasma renin activity, and 24-h urinary aldosterone elimination (U-Aldo) were measured before amlodipine administration; at day 0; and at days 1, 7, 14, 28, 56, and 84 of telmisartan treatment. RESULTS: Telmisartan was associated with significant decreases in systolic blood pressure on day 56 (p=0.046), whereas heart rate did not significantly change during this treatment (p=0.061). Plasma renin activity was significantly increased on days 1, 7, 28, 56, and 84 during telmisartan administration (all p=0.04). No change in median U-Aldo was detected following telmisartan administration (p=0.241). When U-Aldo was evaluated in individual animals, two dogs displayed evidence of aldosterone breakthrough. CONCLUSIONS: Telmisartan administration did not suppress RAAS activation. The appearance of aldosterone breakthrough supports the incomplete blockade of RAAS activation.