Glomerular Lesions in Proteinuric Miniature Schnauzer Dogs.

Miniature Schnauzer dogs are predisposed to idiopathic hypertriglyerceridemia, which increases risk for diseases such as pancreatitis and gallbladder mucocele. Recently, elevated triglyceride concentrations have been associated with proteinuria in this breed, although it is difficult to determine which abnormality is primary. Retrospective review of renal tissue from 27 proteinuric Miniature Schnauzers revealed that 20 dogs had ultrastructural evidence of osmophilic globules consistent with lipid in glomerular tufts. Seven of these dogs had lipid thromboemboli in glomerular capillary loops that distorted their shape and compressed circulating erythrocytes. Triglyceride concentrations were reported in 6 of these 7 dogs, and all were hypertriglyceridemic. In addition, glomerular lipidosis (defined as accumulation of foam cells within peripheral capillary loops) was identified in a single dog. The remaining 12 dogs had smaller amounts of lipid that could only be identified ultrastructurally. Neither signalment data nor clinicopathologic parameters (serum albumin, serum creatinine, urine protein-to-creatinine ratio, and blood pressure) differed among the various types of lipid lesions. During the time course of this study, all dogs diagnosed with glomerular lipid thromboemboli were Miniature Schnauzers, underscoring the importance of recognizing these clear spaces within capillary loops as lipid.

X-Linked Hereditary Nephropathy in Navasota Dogs: Clinical Pathology, Morphology, and Gene Expression During Disease Progression.

X-linked hereditary nephropathy (XLHN) in Navasota dogs is a spontaneously occurring disease caused by a mutation resulting in defective production of type IV collagen and juvenile-onset renal failure. The study was aimed at examining the evolution of renal damage and the expression of selected molecules potentially involved in the pathogenesis of XLHN. Clinical data and renal samples were obtained in 10 XLHN male dogs and 5 controls at 4 (T0), 6 (T1), and 9 (T2) months of age. Glomerular and tubulointerstitial lesions were scored by light microscopy, and the expression of 21 molecules was investigated by quantitative real-time polymerase chain reaction with selected proteins evaluated by immunohistochemistry. No significant histologic lesions or clinicopathologic abnormalities were identified in controls at any time-point. XLHN dogs had progressive proteinuria starting at T0. At T1, XLHN dogs had a mesangioproliferative glomerulopathy with glomerular loss, tubular necrosis, and interstitial fibrosis. At T2, glomerular and tubulointerstitial lesions were more severe, particularly glomerular loss, interstitial fibrosis, and inflammation. At T0, transforming growth factor ß, connective tissue growth factor, and platelet-derived growth factor α mRNA were overexpressed in XLHN dogs compared with controls. Clusterin and TIMP1 transcripts were upregulated in later stages of the disease. Transforming growth factor ß, connective tissue growth factor, and platelet-derived growth factor α should be considered as key players in the initial events of XHLN. Clusterin and TIMP1 appear to be more associated with the progression rather than initiation of tubulointerstitial damage in chronic renal disease.

World Small Animal Veterinary Association Renal Pathology Initiative: Classification of Glomerular Diseases in Dogs.

Evaluation of canine renal biopsy tissue has generally relied on light microscopic (LM) evaluation of hematoxylin and eosin-stained sections ranging in thickness from 3 to 5 µm. Advanced modalities, such as transmission electron microscopy (TEM) and immunofluorescence (IF), have been used sporadically or retrospectively. Diagnostic algorithms of glomerular diseases have been extrapolated from the World Health Organization classification scheme for human glomerular disease. With the recent establishment of 2 veterinary nephropathology services that evaluate 3-µm sections with a panel of histochemical stains and routinely perform TEM and IF, a standardized objective species-specific approach for the diagnosis of canine glomerular disease was needed. Eight veterinary pathologists evaluated 114 parameters (lesions) in renal biopsy specimens from 89 dogs. Hierarchical cluster analysis of the data revealed 2 large categories of glomerular disease based on the presence or absence of immune complex deposition: The immune complex-mediated glomerulonephritis (ICGN) category included cases with histologic lesions of membranoproliferative or membranous patterns. The second category included control dogs and dogs with non-ICGN (glomerular amyloidosis or focal segmental glomerulosclerosis). Cluster analysis performed on only the LM parameters led to misdiagnosis of 22 of the 89 cases-that is, ICGN cases moved to the non-ICGN branch of the dendrogram or vice versa, thereby emphasizing the importance of advanced diagnostic modalities in the evaluation of canine glomerular disease. Salient LM, TEM, and IF features for each pattern of disease were identified, and a preliminary investigation of related clinicopathologic data was performed.

X chromosome inactivation patterns in normal and X-linked hereditary nephropathy carrier dogs.

Alport syndrome (AS) and hereditary nephropathy (HN) are glomerular nephropathies caused by mutations in the genes encoding the type IV collagens. In a mixed breed of dog, termed Navasota (NAV) dogs, X-linked hereditary nephropathy (XLHN) is caused by a 10-bp deletion in exon 9 of COL4A5. Males harboring this mutation succumb to end-stage renal disease before 18 months of age. In contrast, female carriers of this disease survive much longer, most have a normal life-span, and vary in disease progression as compared with XLHN-affected males. X chromosome inactivation (XCI) patterns have been studied in human X-linked AS carriers and some have been shown to have a high degree of skewed XCI. However, similar studies have never been reported in an animal model of this disease. Therefore, patterns of XCI were examined in XLHN-carrier NAV dogs. The variation in XCI among the 26 XLHN-carrier and seven normal female NAV dogs studied was low and only three were found to preferentially inactivate one X chromosome, all of which were XLHN-carriers. The average skewedness among all dogs was 59% and 57% among the XLHN-carriers. No significant difference in XCI was found between the two groups (P = 0.477). It is clear from these data that genotype does not seem to have an effect on inactivation; the majority of these dogs have random patterns of XCI. Highly skewed X chromosome inactivation also appears to be random, given that no difference was observed between the XLHN-carriers and normal females. Because of the apparent rarity of skewed XCI, these dogs may not be a suitable model for studying a potential correlation between this phenomenon and disease progression.

Correlation of Urine and Serum Biomarkers with Renal Damage and Survival in Dogs with Naturally Occurring Proteinuric Chronic Kidney Disease.

BACKGROUND: Urine protein loss is common in dogs with chronic kidney disease (CKD). HYPOTHESIS/OBJECTIVES: To evaluate new biomarkers of glomerular and tubulointerstitial (TI) damage compared with histology and as survival indicators in dogs with naturally occurring, proteinuric CKD. ANIMALS: One hunderd and eighty dogs with naturally occurring kidney disease. METHODS: Retrospective study using urine, serum, and renal biopsies from dogs with kidney disease, 91% of which had proteinuric CKD. Biomarkers were evaluated and correlated with pathologic renal damage, and significant associations, sensitivities, and specificities of biomarkers for renal disease type were determined. RESULTS: Fractional excretions of immunogloblin M (IgM_FE) and immunoglobulin G (IgG_FE) correlated most strongly with glomerular damage based on light microscopy (r = 0.58 and 0.56, respectively; P < .01). Serum creatinine (SCr) correlated most strongly with TI damage (r = 0.70, P < .01). Urine IgM/creatinine and urine NAG/creatinine had the highest sensitivity (75%) and specificity (78%) for detection of immune complex-mediated glomerulonephritis. Although individually most biomarkers were significantly associated with decreased survival time (P < .05), in a multivariate analysis, SCr, IgM_FE, and glomerular damage based on transmission electron microscopy (TEM) were the only biomarkers significantly associated with survival time (SCr: P = .001; IgM_FE: P = .008; TEM: P = .017). CONCLUSIONS AND CLINICAL IMPORTANCE: Novel urine biomarkers and FEs are useful for detection of glomerular and TI damage in dogs with proteinuric CKD and might predict specific disease types and survival.

Symmetric Dimethylarginine Assay Validation, Stability, and Evaluation as a Marker for the Early Detection of Chronic Kidney Disease in Dogs.

BACKGROUND: Symmetric dimethylarginine (SDMA) is a small molecule formed by methylation of arginine, and released into blood during protein degradation. SDMA is primarily eliminated by renal excretion and is a promising endogenous marker of glomerular filtration rate (GFR). OBJECTIVES: To validate an assay for SDMA measurement, determine stability of SDMA in blood, and compare SDMA with serum creatinine concentration (sCr) and GFR for early detection of decreasing kidney function in dogs with chronic kidney disease (CKD). ANIMALS: Eight male dogs affected with X-linked hereditary nephropathy and 4 unaffected male littermates. METHODS: Prospective study validating SDMA measurement using liquid chromatography-mass spectrometry, assessing stability of SDMA in serum and plasma, and serially determining sCr, SDMA, and GFR (using iohexol clearance) in dogs during progression from preclinical disease to end-stage renal failure. Correlations were determined using linear regression. Timepoints at which sCr, SDMA, and GFR identified decreased renal function were compared using defined cutoffs, trending in an individual dog, and comparison with unaffected littermates. RESULTS: Symmetric dimethylarginine was highly stable in serum and plasma, and the assay demonstrated excellent analytical performance. In unaffected dogs, SDMA remained unchanged whereas in affected dogs, SDMA increased during disease progression, correlating strongly with an increase in sCr (r = 0.95) and decrease in GFR (r = -0.95). Although trending improved sCr's sensitivity, SDMA identified, on average, <20% decrease in GFR, which was earlier than sCr using any comparison method. CONCLUSIONS AND CLINICAL IMPORTANCE: Symmetric dimethylarginine is useful for both early identification and monitoring of decreased renal function in dogs with CKD.

Glomerular ultrastructural findings similar to hereditary nephritis in 4 English cocker spaniels.

Renal disease affecting 3 male and 1 female English Cocker Spaniels was studied. Clinical features of the disease included proteinuria and progressive deterioration of renal function. Dogs were 11 to 27 months old when euthanized because of severe chronic renal failure. Grossly, the renal cortices were thin. Light microscopic evaluation revealed diffuse glomerular disease characterized by mesangial thickening, glomerular fibrosis, periglomerular fibrosis, and glomerular obsolescence. Based on these clinical and pathologic features, familial nephropathy of English Cocker Spaniels was suspected despite the fact that the individual dogs were not closely related. On transmission electron microscopy, a distinctive ultrastructural lesion was observed in the glomerular basement membranes (GBM) of all dogs. The GBM exhibited extensive thickening, multilaminar splitting, and fragmentation. Electron dense deposits, suggestive of immunocomplex glomerular disease, were notably absent. A similar ultrastructural GBM lesion is found in human beings and Samoyeds with hereditary nephritis, diseases caused by mutations in the type IV collagen genes. Familial nephropathy in English Cocker Spaniels may be a form of hereditary nephritis caused by a mutation in one of the collagen IV genes.

Evaluation of renal function in cats, using quantitative urinalysis.

Two consecutive 24-hour quantitative urinalyses were performed on each of 12 healthy adult cats to evaluate the technique and obtain reference values for measurements of urinary excretion of several substances. Endogenous creatinine clearance (2.31 +/- 0.47 ml/min/kg) and urinary protein excretion (17.43 +/- 9.05 mg/kg/day) were determined. Additionally, clearances and ratios to creatinine clearances were calculated for phosphate, sodium, potassium, and chloride. The endogenous creatinine clearance value was compared with another estimate of glomerular filtration rate that was based on 99mTc(Sn) diethylene-triaminepentaacetic acid clearance (2.52 +/- 0.58 ml/min/kg). Evaluation of feline renal function, using 24-hour quantitative urinalysis techniques, has potential for clinical application, but has several important limitations as well.

Effects of single-dose and three-day trimethoprim-sulfadiazine and amikacin treatment of induced Escherichia coli urinary tract infections in dogs.

Efficacy of single-dose and 3-day trimethoprim-sulfadiazine (TMS) and amikacin treatment regimens for induced Escherichia coli urinary tract infections (UTI) in dogs was evaluated. Using each regimen, effects of giving TMS combination or amikacin were compared in males and females, and the response of treated dogs was compared with that of nontreated controls. Response to treatment was evaluated, using results of quantitative urine cultures and urinalyses obtained on 4 occasions. Abacteriuria was identified by finding a lack of bacterial organisms in specimens collected for the initial and final posttherapy evaluations. Before treatments, magnitudes of bacteriuria were similar in all experimental groups, and UTI persisted in all nontreated dogs. Single-dose treatment regimens did not reliably eradicate UTI in males or females, whether amikacin or TMS was administered. Magnitude of bacteriuria often diminished immediately after single-dose treatment, and such reductions of bacteriuria persisted in 2 of 8 dogs. However, no male dogs and only 1 of 4 females became abacteriuric after a single-dose treatment regimen. The single female in which UTI was eradicated was treated with a single dose of amikacin. The 3-day TMS treatment regimen eradicated UTI in each of 4 females, but the 3-day amikacin treatment regimen resulted in abacteriuria in only 1 of 4 females. Three-day treatment regimens were not effective in male dogs, regardless of the antimicrobial drug used. Of the short-course treatments for canine UTI evaluated by this model, only 3-day TMS treatment of females was consistently effective.

Simultaneous cystometry and uroflowmetry (micturition study) for evaluation of the caudal part of the urinary tract in dogs: studies of the technique.

A procedure similar to one used for urodynamic evaluation of persons was adapted for simultaneous cystometry and uroflowmetry in dogs. Percutaneous transabdominal urinary bladder catheterizations were used for bladder infusion and cystometry, so that urine flow during voiding would not be altered by urethra instrumentation. The technique was evaluated twice in each of 12 healthy dogs (6 males and 6 females). Studies of individual dogs were performed 1 week apart. Comparisons were made between xylazine and oxymorphone for sedation to accomplish the procedure. Although the 2 drugs provided adequate sedation, oxymorphone was unsatisfactory because it interfered with micturition, whereas xylazine generally did not. Adverse consequences of the procedure occurred infrequently and were minor. According to results of urinalyses, hematuria or pyuria, or both, appeared during the week after the procedure was done in a few dogs, and staphylococcal bacteriuria was induced in 4 dogs. Fluid leakage from urinary bladders was not demonstrated by abdominal paracentesis immediately after each procedure or by contrast radiography performed the day after the 2nd study for each animal. Micturition studies were concluded to be reasonably safe to do, especially when performed by experienced individuals. The studies were judged to have considerable potential value as a means to evaluate lower urinary tract function in dogs.

Simultaneous cystometry and uroflowmetry (micturition study) for evaluation of the caudal part of the urinary tract in dogs: reference values for healthy animals sedated with xylazine.

Micturition studies were performed in 12 healthy dogs (6 females and 6 males). The animals were sedated with xylazine given either IV (1.1 mg/kg) or IM (2.2 mg/kg). Separate antepubic catheters were used to perform bladder infusions and record intravesical pressures. Instantaneous urine flow measurements were obtained, using an apparatus specially designed and constructed for small animals. A total of 45 simultaneous cystometric and uroflowmetric recordings were obtained, and numerical values for 16 different micturition variables were tabulated. The variables were analyzed separately on the basis of sex of the animal, route of administration of the sedative, and the fact of having had a previous bladder instrumentation-micturition study performed. Significant differences within individual dogs were not seen in these analyses. Intravesical pressures, urine flow rates, compliances, and urethral resistance were significantly different (P less than 0.05) between male and female dogs. The micturition study was a simple and reliable urodynamic testing method that could be clinically useful in dogs. In contrast to urodynamic tests previously described in veterinary medicine, this method provided evaluation of the bladder and urethra as a functional unit during both the filling and the emptying phases of micturition. A micturition study should not be regarded as an absolute measure of the physiologic activity of the caudal part of the urinary tract. However, it can provide important additional information for clinical assessment when the lower part of the urinary tract is affected by disease, injury, or drugs.

Effects of dietary sodium intake on blood pressure measurements in partially nephrectomized dogs.

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.

Comparison of four methods of estimating glomerular filtration rate in cats.

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)-diethylene-triaminepentaacetic 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 less than or equal to 0.05). Correlation between ECC and DTPA 2 was not as good (r = 0.783; P less than or equal to 0.10), but the 2 DTPA methods significantly correlated with one another (r = 0.897; P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adverse effects caused by polypropylene and polyvinyl feline urinary catheters.

Effects of 3 days of open dwelling urethral catheterization were evaluated in normal male cats. Commercially manufactured polypropylene and polyvinyl feline urinary catheters of sufficient length to permit constant urine drainage were compared. Catheters were similar in length, diameter, and design. Hematuria occurred in 6 of 6 cats with polypropylene catheters and in 4 of 6 cats with polyvinyl catheters. For cats with polypropylene catheters, hematuria began within 24 hours of catheter insertion. Hematuria induced by polypropylene catheters was usually more severe in final urinalyses than that induced by polyvinyl catheters. Catheter-induced bacteriuria was found in 5 of 6 cats with polypropylene catheters and in 3 of 6 cats with polyvinyl catheters. Staphylococci and streptococci were the most common bacterial isolates. Microscopic lesions in urethras and bladders were significantly less severe in cats with polyvinyl catheters than cats with polypropylene catheters. With few exceptions, urethras of cats with polyvinyl catheters were microscopically indistinguishable from urethras of noncatheterized cats. Polypropylene catheters consistently induced urethritis which was most severe in some bacteriuric cats. Severe lesions were found in the bladders of all cats with polypropylene catheters. Bladder lesions were common in cats with polyvinyl catheters, but were usually less severe in cats with polypropylene catheters. There was no apparent relation between bacteriuria and bladder lesions.

Disposition of clorazepate in dogs after single- and multiple-dose oral administration.

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 less than 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 less than 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 less than 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 less than 0.01) than after a single dose (33 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dietary sodium intake on glomerular filtration rate in partially nephrectomized dogs.

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 in GFR were not observed when dogs were fed the L/H/L or the H/L/H sequence. Therefore, it was concluded that abrupt changes 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.

Comparison of species and numbers of bacteria in concurrently cultured samples of proximal small intestinal fluid and endoscopically obtained duodenal mucosa in dogs with intestinal bacterial overgrowth.

Concurrent bacterial culturing of duodenal/proximal jejunal fluid and duodenal mucosa was performed on 2 occasions in each of 16 IgA-deficient German Shepherd Dogs with small intestinal bacterial overgrowth. The interval between sample collections in each dog was 74 to 78 days. Species of bacteria and numbers of bacterial colony-forming units (CFU) per milliliter of fluid were compared with species and numbers found in the concurrent duodenal mucosa sample. There was inconsistent correlation for number of CFU and minimal correlation for species of bacteria isolated from the 2 sites. Fewer bacterial CFU usually were isolated from the mucosa than from the concurrent fluid sample. When the same numeric criteria used for diagnosing small intestinal bacterial overgrowth in samples of intestinal fluid (ie, > or = 10(5) bacterial or > or = 10(4) anaerobic CFU/ml) were used to interpret results of culturing duodenal mucosa, quantitations of bacterial CFU in duodenal mucosa was found to be a specific, but insensitive test.

Effects of lithium carbonate administration to healthy cats.

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 greater than 2 mEq/L was associated with significant decrease in numbers of circulating segmented neutrophils (less than 1,200 cells/microliter; P less than 0.01) and lymphocytes (less than 1,300 cells/microliter; P less than 0.0001), as well as significant (P less than 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 greater than 2 mEq/L.

Expression of the alpha6 chain of type IV collagen in glomerular basement membranes of healthy adult dogs.

OBJECTIVE: To evaluate expression of the alpha6 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 alpha6(IV) chains and examined by means of fluorescence microscopy. RESULTS: Immunolabeling of the alpha6(IV) chain was not observed in GBM of 6 dogs < or = 30 months old but was observed in GBM of the remaining 6 dogs, all of which were > or = 45 months old. Expression of the alpha6(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 alpha6(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.

New form of X-linked dominant hereditary nephritis in dogs.

OBJECTIVE: To determine features of a new form of hereditary nephritis (HN) in dogs. ANIMALS: Parents and 16 first-generation offspring (8 males, 8 females). PROCEDURE: Adolescent dogs that developed renal failure were euthanatized and necropsied. Unaffected dogs were monitored until they were at least 2 years old. Studies included light and electron microscopy of kidneys obtained from affected and unaffected dogs and immunolabeling for collagen-IV chains in renal and epidermal basement membranes (BM). The nucleotide sequence of a portion of exon 35 of the COL4A5 gene was determined in genomic DNA isolated from affected and unaffected males. RESULTS: 7 of 8 male and 2 of 8 female offspring had proteinuria and juvenile-onset chronic renal failure, which progressed more rapidly in the males. Labeling for alpha3-alpha6(IV) chains was completely absent in renal BM of affected males and segmentally absent in affected females. Expression of alpha1-alpha2(IV) chains in glomerular BM (GBM) of affected dogs was increased. Labeling for alpha5-alpha6(IV) chains in epidermal BM was absent in affected males and segmental in affected females. Ultrastructural changes characteristic of HN were observed in GBM of affected dogs. The sequence of exon 35 of COL4A5 was normal in affected dogs. CONCLUSIONS: This renal disease is an example of X-linked dominant HN, with typical abnormalities of GBM ultrastructure and alpha(IV) chain expression. CLINICAL RELEVANCE AND IMPLICATIONS FOR HUMAN MEDICINE: Dogs with this naturally acquired progressive renal disease can be used to investigate the pathogenesis and treatment of similar disorders in human beings and dogs.