M.J. Fernández del Palacio

Calcium and Phosphorus Homeostasis in Dogs with Spontaneous Chronic Kidney Disease at Different Stages of Severity

BACKGROUND Studies in dogs with experimental chronic kidney disease (CKD) have demonstrated that abnormalities of calcium-phosphorus (Ca-P) homeostasis occur frequently and have a negative effect on kidney function and survival. However, the prevalence of these alterations in dogs with naturally occurring CKD at different stages of severity has not yet been investigated. HYPOTHESIS Abnormalities of Ca-P metabolism occur early in the course of CKD with an increased prevalence in more severe stages. ANIMALS Fifty-four dogs with CKD and 22 healthy dogs. METHODS Blood and urine samples were obtained for a CBC, biochemistry, determination of parathyroid hormone (PTH), calcitriol, and ionized calcium concentrations and urinalysis. Based on urine protein/creatinine ratio and serum creatinine concentration, dogs were grouped according to the IRIS classification for CKD. RESULTS Hyperparathyroidism (HPTH) (PTH > or = 48 pg/mL) was diagnosed in 41 (75.9%) dogs with CKD. Its prevalence increased from 36.4% (stage 1) to 100% (stage 4). Hyperphosphatemia (P > 5.5 mg/dL) was present in 37 (68.5%) dogs; increasing in prevalence from 18% (stage 1) to 100% (stage 4). Receiver-operating characteristic curve analysis showed that serum phosphorus concentration in the 4.5-5.5 mg/dL range correctly identified the presence of HPTH in most dogs. Calcitriol concentration progressively decreased in dogs with CKD and differences became statistically significant by stage 3. CONCLUSION AND CLINICAL RELEVANCE HPTH and hyperphosphatemia occur frequently in dogs with naturally occurring CKD, even at early stages of CKD in some dogs. These findings highlight the importance of monitoring these parameters early in the course of CKD.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study—A Randomized Clinical Trial

Background Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. Hypothesis/Objectives Administration of pimobendan (0.4–0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac‐related death, or euthanasia. Animals 360 client‐owned dogs with MMVD with left atrial‐to‐aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. Methods Prospective, randomized, placebo‐controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac‐related death, or euthanasia. Results Median time to primary endpoint was 1228 days (95% CI: 856–NA) in the pimobendan group and 766 days (95% CI: 667–875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47–0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952–NA) in the pimobendan group and 902 days (95% CI: 747–1061) in the placebo group) (P = .012). Conclusions and Clinical Importance Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

Glomerular Filtration Rate in Dogs with Leishmaniasis and Chronic Kidney Disease

BACKGROUND Glomerular filtration rate (GFR) measurement is an indicator of kidney function. However, its usefulness in dogs at early stages of spontaneous chronic kidney disease (CKD) of glomerular origin, where routine laboratory techniques are not sufficiently sensitive, remains unproved. HYPOTHESIS That GFR is reduced in proteinuric nonazotemic or mildly azotemic dogs with CKD secondary to leishmaniasis. ANIMALS Twenty-six dogs with CKD secondary to leishmaniasis and 10 healthy dogs (control group). METHODS CBC, serum biochemistry, and urinalysis (microalbuminuria and urine protein/creatinine ratio [UPC]) were performed in all dogs. GFR was calculated by measuring exogenous creatinine clearance. Based on degree of proteinuria and serum creatinine concentration (SCr), dogs were classified as group A (control; n = 10): UPC < 0.2, SCr < 1.4 mg/dL; group B (n = 8): UPC, 0.2-0.5, SCr < 1.4 mg/dL; group C (n = 10): UPC > 0.5, SCr < 1.4 mg/dL; group D (n = 5): SCr, 1.4-2 mg/dL; group E (n = 3): SCr > 2 mg/dL. RESULTS GFR (mL/kg/min) was 3.9 +/- 0.29, 4.4 +/- 0.74, 4.5 +/- 1.44, 2.8 +/- 0.97, and 1.5 +/- 0.43 for groups A, B, C, D, and E, respectively. Eleven dogs (1 from group B, 3 from group C, 4 from group D, and all 3 dogs from group E) had an abnormally low GFR. Four dogs from group B and 5 dogs from group C had a GFR above the upper reference range (>4.5 mL/min/kg). CONCLUSION AND CLINICAL RELEVANCE Some proteinuric nonazotemic or mildly azotemic dogs with leishmaniasis have low GFR, but glomerular hyperfiltration occurs in other dogs.

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo : The EPIC Study

Background Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. Objectives To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac‐related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan‐treated dogs differ from dogs receiving placebo at onset of CHF. Animals Three hundred and fifty‐four dogs with MMVD and cardiomegaly. Materials and Methods Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4–0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart‐size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short‐term changes in echocardiographic variables and time to CHF or CRD were explored. Results At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN −0.06 (IQR: −0.15 to +0.02), P < 0.0001, and LA:Ao −0.08 (IQR: −0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. Conclusions and Clinical Importance Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

Evaluation of the effects of a therapeutic renal diet to control proteinuria in proteinuric non-azotemic dogs treated with benazepril.

Background Angiotensin‐converting enzyme inhibitors (ACEIs) are currently used to control proteinuria in dogs with chronic kidney disease. Renal diets (RDs) have beneficial effects in the management of azotemic dogs, but its role in proteinuric non‐azotemic (PNAz) dogs has been poorly documented. Hypothesis Administration of a RD to PNAz dogs treated with benazepril (Be) improves proteinuria control compared with the administration of a maintenance diet (MD). Animals Twenty‐two PNAz (urine protein/creatinine ratio [UPC] >1) dogs. Methods Randomized open label clinical trial design. Dogs were assigned to group‐MD (5.5 g protein/100 kcal ME)/Be or to group‐RD (3.7 g protein/100 kcal ME)/Be group during 60 days. Dogs with serum albumin (Alb) <2 g/dL received aspirin (1 mg/kg/12 hours). A physical examination, systolic blood pressure (SBP) measurement, complete blood count (CBC), biochemistry panel, urinalysis, and UPC were performed at day 0 (D0) and day 60 (D60). Results At D0, there were no significant differences between groups in the evaluated variables. During the study, logUPC (geometric mean (95% CI) and SBP (mean±SD mmHg) significantly decreased (paired t‐test, P = 0.001) in Group‐RD (logUPCD0 = 3.16[1.9–5.25]; UPCD60 = 1.20 [0.59–2.45]; SBPD0 = 160 ± 17.2; SBPD60 = 151 ± 15.8), but not in Group‐MD (UPCD0 = 3.63[2.69–4.9]; UPCD60 = 2.14 [0.76–6.17]; SBPD0 = 158 ± 14.7; SBPD60 = 153 ± 11.5). However, RM‐ANOVA test did not confirm that changes were consequence of dietary modification. Weight and Alb concentration did not change significantly in any group. Conclusion and Clinical Relevance The administration of a RD to PNAz dogs treated with Be might help to control proteinuria and SBP compared with the administration of a MD, without inducing clinically detectable malnutrition, but more studies are warranted.

Effects of sedation with acepromazine maleate and buprenorphine hydrochloride on femoral artery blood flow in healthy dogs

The purpose of this study was to qualify and quantify the femoral artery blood flow by duplex Doppler ultrasonography (DDU) in healthy dogs, before and after the administration of a combination of acepromazine maleate and buprenorphine hydrochloride (ACP-BPN). Seven healthy adult mongrel dogs and three adult beagles were used. Heart rate, arterial blood pressure and measurement of femoral artery blood flow by DDU were also recorded. The DDU measurements were: femoral artery diameter (FAD), peak systolic velocity (PSV), early retrograde (EDV) and end diastolic velocities (EnDV), mean velocity (BMV), pulsatility index (PI), flow velocity integral (FVI) and femoral blood flow (FBF). After 30 min, combination ACP-BPN was administered intramuscularly, and all the measurements were recorded again. The ACP-BPN protocol induced a significant decrease in systolic, mean, and diastolic arterial blood pressure, and heart rate. A significant increase in peak systolic velocity and integral flow velocity integral of the femoral blood were obtained. The Doppler spectra of the blood flow in the femoral artery revealed a spectral dispersion pattern after ACP-BPN administration in all the dogs. These results demonstrate that despite quantitative and qualitative changes, the overall femoral blood flow (FBF) is not significantly modified.