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in Journal of the American Veterinary Medical Association

Summary

Systolic, diastolic, and mean arterial blood pressure were measured by femoral artery puncture every other day in 2 groups (n = 4) of partially nephrectomized (approx 75%) dogs fed 2 concentrations of dietary sodium beginning 9 weeks after partial nephrectomy was completed. In a double crossover design, dogs were fed a low-sodium (0.18% sodium on a dry-weight basis) or high-sodium (1.3% sodium on a dry-weight basis) diet in 2 sequences (l/h/l or h/l/h) for 3 consecutive 4-week observation periods. Significant effect of sequence was found in dogs fed the l/h/l sequence, compared with those fed the h/l/h sequence. Systolic blood pressure was significantly (P < 0.05) increased in dogs fed the l/h/l sequence (175 ± 16 mm of Hg), compared with dogs fed the h/l/h sequence (156 ± 14 mm of Hg). Mean arterial blood pressure was higher, but not significantly different, for the l/h/l sequence (116 ± 8 mm of Hg) vs the h/l/h sequence (109 ± 6 mm of Hg). Significant difference in diastolic pressure was not observed between the l/h/l (86 ± 10 mm of Hg) and h/l/h (86 ± 10 mm of Hg) sequences. Restricted sodium intake (0.18% sodium on a dry-weight basis) was associated with moderate systolic hypertension in dogs with experimentally induced chronic renal disease. Acute fluctuations in dietary sodium intake had no apparent immediate effect on blood pressure in dogs with this mild to moderate degree of renal dysfunction.

Free access
in American Journal of Veterinary Research

SUMMARY

Clorazepate dipotassium was administered orally to 8 healthy dogs at a dosage of 2 mg/kg of body weight, q 12 h, for 21 days. Serum disposition of nordiazepam, the principle metabolite of clorazepate, was determined after the first and last dose of clorazepate. Disposition variables were analyzed by use of model-independent pharmacokinetics by the predictive equations method and the trapezoidal rule method. Complete blood counts, serum chemical analyses, and urinalyses were performed before administration of clorazepate and at 10 and 21 days after administration of clorazepate.

Maximal nordiazepam concentrations ranged from 446 to 1,542 ng/ml (814 ± 334 ng/ml), at 59 to 180 minutes (97.9 ± 42.0 minutes) after a single oral dose of clorazepate. Maximal nordiazepam concentrations ranged from 927 to 1,460 ng/ml (1,308 ± 187.6 ng/ml), at 120 to 239 minutes (153 ± 57.9 minutes) after multiple oral doses of clorazepate. Serum disposition was significantly altered after multiple doses of clorazepate. Using data determined by the predictive equations method, the mean residence time after multiple doses (712 ± 214 minutes) was longer (P < 0.05) than after a single dose (527 ± 95.8 minutes). Oral volume of distribution after multiple doses of clorazepate (1.76 ± 0.647 L/kg) was smaller (P < 0.02) than after a single dose (3.18 ± 1.52 L/kg). Oral clearance after multiple doses of clorazepate (3.09 ± 0.726 ml/min/kg) was less (P < 0.001) than after a single dose (6.54 ± 2.15 ml/min/kg). Absorption half-life after multiple doses (72 minutes) was longer (P < 0.01) than after a single dose (33 minutes). The elimination half-life after a single dose (284 minutes) was not significantly different after multiple doses (355 minutes).

Significant changes (P < 0.05) in serum chemical values after multiple doses of clorazepate included decreased concentrations of albumin, total protein, and calcium and increased concentrations of urea nitrogen and glucose. Serum activities of alkaline phosphatase and alanine transaminase increased after multiple doses of clorazepate. Significant changes (P < 0.05) in the hemogram included increased total wbc count, segmented neutrophils, lymphocytes, and eosinophils. Urine pH after multiple doses (5.88 ± 0.641) was lower (P < 0.01) than after a single dose (7.44 ± 1.29). All changes in laboratory values remained within our reference ranges.

Mild sedation and ataxia developed in only 1 dog after the first dose of clorazepate. These effects were transient and did not redevelop with additional dosing.

An oral clorazepate dosage of 2 mg/kg, q 12 h, maintains serum nordiazepam concentrations considered to be therapeutic in human beings (500 to 1,900 ng/ml).

Free access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate expression of the α6 chain of type IV collagen in the glomerular basement membranes (GBM) of healthy dogs.

Sample Population—Kidney specimens from 12 healthy dogs. For comparison, kidney specimens from 8 human subjects between 25 and 83 years old also were evaluated.

Procedure—Sections were immunolabeled with a monospecific antibody that cross-reacts with human and canine α6(IV) chains and examined by means of fluorescence microscopy.

Results—Immunolabeling of the α6(IV) chain was not observed in GBM of 6 dogs ≤ 30 months old but was observed in GBM of the remaining 6 dogs, all of which were ≥ 45 months old. Expression of the α6(IV) chain was not observed in GBM of the human subjects, regardless of the age of the subject.

Conclusions and Clinical Relevance—Results indicate that the α6(IV) chain is expressed in GBM of healthy dogs, but the expression is age-dependent. Composition and structural organization of type IV collagen in the GBM of healthy adult dogs is different from that described for other species. (Am J Vet Res 2000;61:38–41)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate stability of canine pancreatic lipase immunoreactivity (cPLI) in serum samples and to determine the effect of long-term administration of prednisone on serum cPLI concentrations.

Sample Population—8 canine serum samples for the stability evaluation and serum samples obtained from 6 healthy young adult heterozygous (carrier) dogs with X-linked hereditary nephritis for determining the effect of prednisone administration.

Procedures—To evaluate stability of serum cPLI concentration, an aliquot of each serum sample was stored at each of 4 temperatures between −80° and 24°C; samples were analyzed on days 0, 3, 7, 14, and 21. To determine the effect of long-term prednisone administration, pretreatment serum samples were obtained (days 0 and 14) and prednisone was administered (2.2 mg/kg, q 24 h, PO) on days 15 through 42, with serum samples obtained on days 28 and 42. Additional serum samples were obtained on days 56 and 70.

Results—Mean serum cPLI concentrations did not change significantly from day 0 to day 21 regardless of storage temperature. Serum cPLI concentrations in dogs after prednisone administration were within the reference range for all dogs at all time points, and results of repeated-measures ANOVA revealed that serum cPLI concentrations did not change significantly over time.

Conclusions and Clinical Relevance—Serum cPLI concentrations measured in canine serum samples stored at room temperature, in a refrigerator, or in a freezer at −20° or −80°C were stable for at least 21 days. Also, long-term prednisone administration to dogs did not significantly affect serum cPLI concentrations.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate perinuclear anti-neutrophilic cytoplasmic autoantibody (pANCA) status in Soft Coated Wheaten Terriers (SCWTs) and SCWT-Beagle crossbred dogs and to correlate pANCA status of dogs with clinicopathologic variables of protein-losing enteropathy (PLE), protein-losing nephropathy (PLN), or both.

Animals—13 SCWTs and 8 SCWT-Beagle crossbred dogs in a research colony and a control group comprising 7 dogs with X-linked hereditary nephropathy and 12 healthy SCWTs > 9 years old.

Procedures—Samples were obtained from dogs in the research colony every 6 months. At each sample-collection time point, serum concentrations of albumin, globulin, creatinine, and urea nitrogen; fecal concentration of α-proteinase inhibitor; and urinary protein-to-creatinine ratios were determined and correlated with pANCA status.

Results—20 of 21 dogs in the research colony had positive results for pANCAs at a minimum of 2 time points, and 18 of 21 dogs had definitive evidence of disease. None of the control dogs had positive results for pANCAs. A positive result for pANCAs was significantly associated with hypoalbuminemia, and pANCAs preceded the onset of hypoalbuminemia on an average of 2.4 years. Sensitivity and specificity for use of pANCAs to predict development of PLE or PLN were 0.95 (95% confidence interval, 0.72 to 1.00) and 0.8 (95% confidence interval, 0.51 to 0.95), respectively.

Conclusions and Clinical Relevance—Most dogs in this study affected with PLE, PLN, or both had positive results for pANCAs before clinicopathologic evidence of disease was detected. Thus, pANCAs may be useful as an early noninvasive test of disease in SCWTs.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To identify factors affecting the diagnostic quality of core needle renal biopsy specimens from dogs with suspected kidney disease.

DESIGN Cross-sectional study.

ANIMALS 522 client-owned dogs with suspected kidney disease for which core needle renal biopsy specimens (n = 1,089) were submitted to the International Veterinary Renal Pathology Service for evaluation and inclusion in their database.

PROCEDURES Data regarding dog signalment, clinical variables, biopsy method, needle brand and gauge, biopsy results, and other variables were extracted from the database. Variables were tested for association with 3 outcomes of light microscopic evaluation of core specimens: number of glomeruli per core specimen, obtainment of < 10 glomeruli, and presence or absence of renal medullary tissue.

RESULTS Number of glomeruli per core specimen was significantly associated with needle gauge, dog age, serum creatinine concentration, and degree of proteinuria, whereas biopsy method and submitting hospital were significantly associated with the presence of renal medullary tissue in specimens. Mean numbers of glomeruli per core specimen obtained with 14- or 16-gauge needles were similar, but both were significantly greater than the mean number obtained with 18-gauge needles. Needle gauge had a similar association with the likelihood of obtaining < 10 glomeruli in a core specimen. Specimens obtained via laparotomy or laparoscopic approaches more commonly contained medullary tissue than those obtained by ultrasound-guided approaches.

CONCLUSIONS AND CLINICAL RELEVANCE Overall, findings suggested that ultrasound-guided biopsy with a 16-gauge needle should maximize the diagnostic quality of renal biopsy specimens from dogs with suspected kidney disease, while avoiding potential adverse effects caused by larger needles.

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in Journal of the American Veterinary Medical Association

SUMMARY

Four methods of evaluating renal function were performed in 6 cats anesthetized with halothane in oxygen. Glomerular filtration rate (gfr) was measured simultaneously in each cat by exogenous creatinine clearance (ecc), bolus inulin clearance, and 99mTc(Sn)-diethylenetriaminepentaacetic acid (dtpa) clearance determined by 2 different methods. In the first dtpa clearance method (dtpa-1), we measured radioactivity in serial blood specimens to construct plasma disappearance curves for calculation of gfr. In the second dtpa clearance method (dtpa-2), we used serial external head counts of radioactivity and a single blood specimen to construct plasma disappearance curves for calculation of gfr. Bolus inulin clearance was calculated from plasma disappearance curves using a 1-compartment open pharmacokinetic model (IN- 1) and a 2-compartment open pharmacokinetic model (IN- 2). Glomerular filtration rates were measured over 3 hours, for creatinine and dtpa methods, and over 4 hours for the inulin methods.

The gfr obtained with the reference method (ecc) was 2.56 ± 0.61 ml/min/kg of body weight (mean ± SD). Values for gfr determined by ecc and dtpa-1 were significantly correlated (r = 0.852; P ≤ 0.05). Correlation between ecc and dtpa 2 was not as good (r = 0.783; P ≤ 0.10), but the 2 dtpa methods significantly correlated with one another (r = 0.897; P ≤ 0.05). Regardless of the method of calculation, bolus inulin clearance was poorly correlated with ecc (IN-1: r = 0.538, P ≥ 0.10; in-2: r = 0.430, P ≥ 0.10) and dtpa-1 in-1: r = 0.601, P ≥ 0.10; in-2: r = 0.625, P ≥ 0.10). The 2 methods of calculating inulin clearance were highly correlated (r = 0.927; P ≤ 0.01). The dtpa clearance calculated from directly measured plasma disappearance curves (dtpa-1) compared favorably with ecc as an estimate of gfr and appears to be a safe, reliable, and less invasive method of determining gfr in cats.

Free access
in American Journal of Veterinary Research

Summary

Lithium carbonate administration to healthy cats was evaluated in 2 controlled studies (a dose-response study and a bone marrow evaluation study) to determine the effectiveness of lithium as a bone marrow stimulant. Lithium carbonate was administrated at dosage ranging from 300 to 1,050 mg/m2 of body surface/d. Complete blood count, serum lithium concentration determination, serum biochemical analysis, urinalysis, and bone marrow aspiration and biopsy were periodically performed.

Serum lithium concentration > 2 mEq/L was associated with significant decrease in numbers of circulating segmented neutrophils (< 1,200 cells/μl; P < 0.01) and lymphocytes (< 1,300 cells/μl; P < 0.0001), as well as significant (P < 0.05) decrease in urine specific gravity. Bone marrow evaluation revealed apparent maturation arrest of the neutrophil cell line.

Coincident with the changes in laboratory values, the lithium-treated cats became ill. Changes in behavior and vocalization were seen, followed by anorexia, vomiting, and diarrhea. In later stages of intoxication, cats became hyperexcitable and manifested coarse muscular tremors. It was concluded that lithium carbonate does not have potential value as a bone marrow stimulant and is toxic to cats at serum concentration > 2 mEq/L.

Free access
in American Journal of Veterinary Research

Summary

Exogenous creatinine clearance rate was determined in 8 partially (approx 75%) nephrectomized dogs fed 2 concentrations of dietary sodium, beginning 9 weeks after partial nephrectomy was performed. In a double crossover design, dogs were then fed low-sodium diet (0.18% sodium on a dry-weight basis) or high-sodium diet (1.3% sodium on a dry-weight basis) in 2 sequences (l/h/l or h/l/h) for 3 consecutive 4-week observation periods. Glomerular filtration rate (gfr) was measured by exogenous creatinine clearance before and after partial nephrectomy, and every 2 weeks during the experimental diet periods. Initial mean ± sd gfr (3.76 ± 0.78 ml/min/kg of body weight) decreased precipitously after nephrectomy (1.25 ± 0.45 ml/min/kg); however, during the postnephrectomy and experimental diet periods, gfr gradually increased in all dogs to nearly half the prenephrectomy values (1.87 ± 0.22 ml/min/kg). Significant differences ingfr were not observed when dogs were fed the l/h/l or the h/l/h sequence. Therefore, it was concluded that abrupt change from high dietary sodium (1.3%) to restricted dietary sodium (0.18%), or vice versa, does not cause deterioration of renal function in dogs with moderate renal impairment. However, caution should be used in extrapolating these findings to dogs with clinically evident (azotemia, isosthenuria) renal failure.

Free access
in American Journal of Veterinary Research