Hervé P. Lefebvre

Association of Plasma N-Terminal Pro-B-Type Natriuretic Peptide Concentration with Mitral Regurgitation Severity and Outcome in Dogs with Asymptomatic Degenerative Mitral Valve Disease

BACKGROUND The clinical outcome of dogs affected by degenerative mitral valve disease (MVD) without overt clinical signs is still poorly defined, and criteria for identification of animals that are at a higher risk of early decompensation have not yet been determined. HYPOTHESIS N-terminal pro-B-type natriuretic peptide plasma concentration (NT-proBNP) is correlated with mitral regurgitation (MR) severity and can predict disease progression in dogs with asymptomatic MVD. ANIMALS Seventy-two dogs with asymptomatic MVD, with or without heart enlargement (International Small Animal Cardiac Health Council: ISACHC classes 1a and 1b), and a control group of 22 dogs were prospectively recruited. METHODS Severity of MR was quantitatively assessed from the regurgitation fraction (RF) by the proximal isovelocity surface area method. Consequences of MR were evaluated from measurements of the left atrium/aorta ratio (LA/Ao), fractional shortening (FS), end-diastolic and end-systolic left ventricular volumes indexed to body surface area (EDVI and ESVI). The relevance of these echo-Doppler indices and NT-proBNP for prediction of outcome at 12 months was studied. RESULTS A significant correlation was found between NT-proBNP and RF, LA/Ao, FS, and EDVI (P < .05). NT-proBNP was higher in dogs with MVD (ISACHC classes 1a and 1b) compared with the control group (P= .025 and < .001, respectively). The difference was not significant when only dogs from ISACHC class 1a with RF < 30% were considered. Lastly, NT-proBNP was higher in dogs that underwent MVD decompensation at 12 months (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE NT-proBNP is correlated with MVD severity and prognosis in dogs with asymptomatic MVD.

Plasma N-terminal pro-B-type natriuretic peptide concentration helps to predict survival in dogs with symptomatic degenerative mitral valve disease regardless of and in combination with the initial clinical status at admission.

OBJECTIVES Although mitral valve disease (MVD) is the most common canine heart disease, readily available prognostic markers of the disease are still lacking. The aim of this study was to evaluate the comparative ability of N-terminal pro-B-type natriuretic peptide plasma concentration (NT-proBNP) and various echocardiographic variables to predict outcome in dogs with MVD. ANIMALS, MATERIALS AND METHODS Seventy-four dogs with ISACHC classes 2 and 3 MVD (Groups A and B, respectively) were prospectively recruited. NT-proBNP and several echo-Doppler variables at inclusion were compared as predictors of outcome at 6 months in 54/74 dogs. RESULTS NT-proBNP was significantly higher in Group B than in Group A (P<0.0001), and was the only tested variable significantly different between survivor and non-survivor dogs in both groups (P<0.05). In the whole canine population, a threshold of 1500 pmol/L could discriminate survivor from non-survivor dogs with a sensitivity and specificity of 80% and 73%, respectively. When combining ISACHC class with NT-proBNP levels, a cut-off of 1265 pmol/L was predictive of survival in Group A, whereas the cut-off was 2700 pmol/L for Group B. CONCLUSIONS NT-proBNP is correlated with MVD severity and could be used in combination with clinical status to predict cardiac outcome.

Short- and long-term follow-up of glomerular and tubular renal markers of kidney function in hyperthyroid cats after treatment with radioiodine ☆

Hyperthyroidism can mask co-existing chronic kidney disease (CKD). Previous studies showed that post-treatment renal azotemia can be predicted by pre-treatment assessment of glomerular filtration rate (GFR). We hypothesized that treatment of hyperthyroidism may have different effects on glomerular and tubular function and these changes might be predicted by additional pre-treatment variables than GFR. Serum total T4 (TT4), creatinine and blood urea nitrogen (BUN), blood pressure (BP), body weight (BW), GFR, urine specific gravity (USG), urinary protein/creatinine ratio (UPC) and retinol binding protein/creatinine ratio (uRBP/c) were evaluated before and 1, 4, 12 and 24 weeks post-treatment with radioiodine ((131)I) in 21 non-azotemic hyperthyroid cats. Cats were divided 24 weeks post-treatment into group A (normal kidney function, n=16) and group B (impaired kidney function, n=5). Serum TT4, GFR, UPC and uRBP/c decreased significantly after treatment for the complete group and group A (P<0.05), although GFR and uRBP/c did not change in group B. Serum creatinine and BW increased significantly from 1 week after treatment (P<0.05). There was no change in BUN, USG or BP. Pre-treatment serum TT4, GFR and USG differed significantly between group A and B (P<0.05). GFR at 4 weeks after treatment and maximum decrease in GFR could be partially predicted by a formula using pre-treatment GFR, serum TT4, serum creatinine, BUN and/or USG. Significant changes in kidney function occur within 4 weeks post-treatment and none thereafter. Pre-treatment measurement of GFR, USG and serum TT4 can have possible predictive value regarding the development of post-treatment renal azotemia.

Fractional excretion tests: a critical review of methods and applications in domestic animals

The fractional excretion (FE) of a constituent by the kidney is the fraction of the amount filtered by the glomerulus, which is excreted into urine. It is mostly determined for electrolytes, and is expressed as the ratio of the clearance of a given electrolyte to creatinine clearance. The main physiologic factors affecting FE variation are species, age, and the alimentary supply of electrolytes. The value of FE tests in the diagnosis of kidney disease is limited, except in canine Fanconis syndrome. FEs of many constituents often are increased in chronic kidney disease, but their diagnostic value is no greater than that of plasma creatinine concentration. FEs also are altered in nonrenal diseases such as diabetes mellitus and rhabdomyolysis, and during treatment with xylazine, rehydration fluids, and diuretics. FEs, especially of calcium, phosphates, and magnesium, are useful in clinical nutrition to assess mineral balance. FE is difficult to measure, so its use should be limited to nutritional investigations and nephrology research.

Disposition of plasma creatinine in non-azotaemic and moderately azotaemic cats

The objectives of this study were to compare assay methods for plasma creatinine (Pl-creat) in cats and to describe the disposition of creatinine and iohexol in 12 healthy and moderately azotaemic cats. Exogenous creatinine and iohexol were injected simultaneously by intravenous bolus, and repeated blood samples were taken to determine the pharmacokinetic parameters of each marker. Pl-creat was assayed by high-performance liquid chromatography (HPLC), Jaffé and enzymatic methods. The enzymatic method was shown to be more reliable than the Jaffé method. Two stereoisomers, exo- and endo-iohexol were identified. The plasma clearance of creatinine (2.3±0.66 ml/min/kg) was significantly higher (P<0.001) than that of exo-iohexol (1.7±0.40 ml/min/kg). The volume of distribution (447±97 ml/kg) and elimination half-life (181±77 min) of creatinine were also higher (P<0.001) than those of exo- and endo-iohexol. The estimated daily endogenous production of creatinine was 65±23 mg/kg. None of the pharmacokinetic parameters was changed by the azotaemic status of the animals.

Angiotensin-converting enzyme inhibitors in veterinary medicine.

Angiotensin-converting enzyme (ACE) inhibitors represent one of the most commonly used categories of drugs in canine and feline medicine. ACE inhibitors currently approved for use in veterinary medicine are benazepril, enalapril, imidapril and ramipril. They are all pro-drugs administered by oral route. A physiologically based model taking into account the saturable binding to ACE has been developed for pharmacokinetic analysis. The bioavailability of the active compounds from their respective pro-drug is low. The active metabolites are eliminated by renal, hepatorenal or biliary excretion, according to the drug. The elimination half-life of the free fraction of the active compounds is very short (ranging from approximately 10 min to 2 h). ACE inhibitors are generally well tolerated. Benazepril, enalapril, imidapril and ramipril are approved for dogs with chronic heart failure (CHF). The efficacy of ACE inhibitors has been convincingly demonstrated in dogs with CHF, especially in those with chronic valvular disease. In such clinical settings, ACE inhibitors improve hemodynamics and clinical signs, and increase survival time. In cats with cardiovascular disease, little information is available except for reports of some benefit in cats with hypertrophic cardiomyopathy in two non-controlled investigations. ACE inhibitors have also a mild to moderate hypotensive effect. There is also evidence to recommend ACE inhibitors in dogs and cats with chronic renal failure (CRF). They decrease the glomerular capillary pressure, have antiproteinuric effects, tend to delay the progression of CRF and to limit the extent of renal lesions.

Plasma clearance of exogenous creatinine, exo-iohexol, and endo-iohexol in hyperthyroid cats before and after treatment with radioiodine

BACKGROUND Glomerular filtration rate (GFR) can be measured by clearance methods of different markers showing discrepancies and different reproducibility in healthy cats. Studies comparing different methods of GFR measurement in hyperthyroid cats have not yet been performed. HYPOTHESIS Plasma clearance of exogenous creatinine (PECCT), exo-iohexol (PexICT), and endo-iohexol (PenICT) could lead to differences in GFR measurement and the need to use the same clearance method when comparing GFR before and after radioiodine treatment in hyperthyroid cats. ANIMALS Fifteen client-owned hyperthyroid cats. METHODS GFR was measured 1 day before and 1, 4, 12, and 24 weeks after treatment. Intravenous injection of iohexol was followed immediately by IV injection of creatinine. Plasma creatinine was measured by an enzymatic method. Plasma endo- and exo-iohexol were measured by high-performance liquid chromatography coupled to ultraviolet detection. RESULTS Globally, the 3 GFR methods resulted in significantly different (P < .001) GFR results. GFR results among the different methods were the same (P= .999) at all time points. All 3 techniques indicated decreasing GFR after (131)I treatment. For each GFR technique, a significant decrease in GFR was observed between time point 0 and all other time points. This decrease stabilized 4 weeks after treatment, with very little decline afterward. CONCLUSION AND CLINICAL IMPORTANCE It is mandatory to use the same GFR technique in follow-up studies. GFR testing at 4 weeks posttreatment could allow assessment of the final renal functional loss after treatment in hyperthyroid cats.

Effect of benazepril on survival and cardiac events in dogs with asymptomatic mitral valve disease: a retrospective study of 141 cases.

BACKGROUND Angiotensin-converting enzyme inhibitors (ACEIs) improve quality of life and extend the life span of dogs with naturally acquired ISACHC class II-III congestive heart failure (CHF). However, their effects on asymptomatic heart disease remain controversial. HYPOTHESIS Benazepril (BNZ), an ACEI, could have beneficial effects at the asymptomatic stage of degenerative mitral valve disease (MVD). ANIMALS Dogs with ISACHC class Ia MVD and moderate-to-severe mitral regurgitation (MR) assessed by the color Doppler mapping technique at entry (Day 0) were retrospectively included. METHODS Dogs were assigned to the treated group (BNZ group) if they received BNZ (and no other cardiac medication) from Day 0 or to the untreated group (UT group) if they did not receive any cardioactive treatment until occurrence of CHF. RESULTS A total of 141 dogs were included in the study, 66 in the BNZ group (dosage: 0.30 +/- 0.13 mg/kg) and 75 in the UT group. In the population (n = 93) including all breeds except Cavalier (CKC) and King Charles Spaniels (KC), median survival time to all causes of death in the BNZ group (n = 34, 3.3 years) was significantly longer than in the UT group (n = 59, 1.9 years) as was time to cardiac event (P < .05). Conversely, no effect of the BNZ treatment was observed in the CKC and KC population. CONCLUSIONS AND CLINICAL RELEVANCE BNZ had beneficial effects in asymptomatic dogs other than CKC and KC affected by MVD with moderate-to-severe MR. Breed distribution should be taken into account for interpretation of clinical trials performed in dogs with cardiac disease.

Effect of Thyroxine Supplementation on Glomerular Filtration Rate in Hypothyroid Dogs

BACKGROUND Glomerular filtration rate (GFR) is decreased in humans with hypothyroidism, but information about kidney function in dogs with hypothyroidism is lacking. HYPOTHESIS Hypothyroidism influences GFR in dogs. The objective of this study was to assess GFR in hypothyroid dogs before implementation of thyroxine supplementation and after re-establishing euthyroidism. ANIMALS Fourteen hypothyroid dogs without abnormalities on renal ultrasound examination or urinalysis. METHODS Blood pressure and GFR (measured by exogenous creatinine clearance) were measured before treatment (T0, n=14) and at 1 month (T1, n=14) and at 6 months (T6, n=11) after beginning levothyroxine supplementation therapy (20 microg/kg/d, PO). The response to therapy was monitored at T1 by measuring serum total thyroxine and thyroid stimulating hormone concentrations. If needed, levothyroxine dosage was adjusted and reassessed after 1 month. Statistical analysis was performed using a general linear model. Results are expressed as mean+/-standard deviation. RESULTS At T0, the average age of dogs in the study group was 6.3+/-1.4 years. Their average body weight decreased from 35+/-18 kg at T0 to 27+/-14 kg at T6 (P<.05). All dogs remained normotensive throughout the study. GFR increased significantly with levothyroxine supplementation; the corresponding results were 1.6+/-0.4 mL/min/kg at T0, 2.1+/-0.4 at T1, and 2.0+/-0.4 at T6 (P<.01). CONCLUSION GFR was <2 mL/min/kg in untreated hypothyroid dogs. Re-establishment of a euthyroid state increased GFR significantly.

Effects of Dietary Salt Intake on Renal Function: A 2-Year Study in Healthy Aged Cats

BACKGROUND Increasing salt intake to promote diuresis has been suggested in the management of feline lower urinary tract disease. However, high dietary salt intake might adversely affect blood pressure and renal function. OBJECTIVES The objective of this study was to assess the long-term effects of increased salt intake on renal function in healthy aged cats. METHODS This study was controlled, randomized, and blinded. Twenty healthy neutered cats (10.1 ± 2.4 years) were randomly allocated into 2 matched groups. One group was fed a high salt diet (3.1 g/Mcal sodium, 5.5 g/Mcal chloride) and the other a control diet of same composition except for salt content (1.0 g/Mcal sodium, 2.2 g/Mcal chloride). Clinical examination, glomerular filtration rate, blood pressure measurement, cardiac and kidney ultrasonography, and urinary and blood tests were performed before and over 24 months after diet implementation. Statistics were performed using a general linear model. RESULTS Sixteen cats completed the 2 year study. The only variables affected by dietary salt intake were plasma aldosterone and urinary sodium/creatinine ratio, respectively, higher and lower in the control group all over the study period and urinary specific gravity, lower in the high salt diet group at 3 months. CONCLUSIONS AND CLINICAL IMPORTANCE Glomerular filtration rate (GFR), blood pressure, and other routine clinical pathological variables in healthy aged cats were not affected by dietary salt content. The results of this 2 year study do not support the suggestion that chronic increases in dietary salt intake are harmful to renal function in older cats.