To determine the role of thromboxane A2 in the pathogenesis of experimentally induced immune complex glomerulonephritis, 12 concanavalin A-immunized Beagles were infused with 1 mg of concanavalin A via each renal artery and treated twice daily for 8 days with either 30 mg of CGS 12970/kg, PO, a specific thromboxane synthetase inhibitor, or placebo. The effect of treatment was assessed by measuring endogenous creatinine clearance and urine protein and eicosanoid excretion, and by evaluating changes in glomerular morphometric characteristics. On postinfusion day 8, urine protein, thromboxane B2, and 11-dehydro-thromboxane B2 excretion, glomerular epithelial crescent formation, and glomerular cell proliferation in the CGS 12970-treated dogs were significantly decreased when compared with values in the placebo-treated group. Differences were not observed in endogenous creatinine clearance, urine prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, or glomerular polymorphonuclear leukocyte infiltration between groups in this study. These findings suggest thromboxane A2 has a role in the development of immune complex glomerulonephritis and that thromboxane synthetase inhibition may be beneficial in attenuating some of the functional and histologic changes associated with immune complex glomerulonephritis.

In order to investigate the renal pathology of spontaneously occurring renal lesions, basic macroscopic inspection was conducted to 3,850 pigs randomly collected from local slaughter houses, and a total of 355 pigs (9.2 %) were detected with various gross pathological conditions. Renal morphologic patterns for gross lesions were classified histopathologically as 123 (34.5 %) congestion, 81 (22.8 %) acute interstitial nephritis, 52 (14.7 %) chronic interstitial nephritis, 49 (13.8 %) hemorrhage, 39 (11.0 %) renal cyst, 29 (8.2 %) chronic glomerulonephritis, 18 (5.1 %) acute glomeruonephritis, 14 (3.9 %) infarction, 11 (3.1 %) thrombosis, 5 (1.4 %) atrophy, 5 (1.4 %) pyelonephritis and 1 (0.3 %) lymphosarcoma.

A 1-year and 6-month-old, intact male, Shit-tzu dog was referred to the Konkuk University Veterinary Teaching Hospital, due to ascite, melena, severe anemia, and polyuria/polydipsia. Complete blood count showed moderate leukocytosis, lymphocytosis, monocytosis, and microcytic hypochromic nonregenerative anemia. On serum biochemistry profiles, hypoalbuminema and hypoproteinemia were observed, and proteinuria was detected on urinalysis.

Nine 7-month-old Beagle dogs were inoculated with 200 third-stage larvae of Dirofilaria immitis. The development of cardiac disease secondary to heartworm infection was confirmed by thoracic radiography, echocardiography, and angiography with blood pressure measurements. The only indication of renal disease was mild-to-moderate proteinuria. The dogs were euthanatized approximately 18 months after inoculation. The mean microfilarial count in blood at the time of euthanasia was 88,700/ml, with a mean of 89 adult heartworms in the vena cavae, heart, and pulmonary arteries. The kidneys were perfused for microangiographic and correlative histologic examination of the intrarenal microvasculature and associated renal morphologic features. Angiograms of whole kidneys from 6 dogs revealed attenuation or truncation of the major renal vessels. Microangiograms of all kidney slices revealed attenuation in the microangiographic appearance of the glomerular capillaries. Histologic examination of all kidney slices revealed mild-to-intense, diffuse, chronic interstitial nephritis and generalized membranoproliferative glomerulonephritis. Microfilariae were observed within the glomerular capillaries and the medullary vessels. The microangiographic changes correlated with and were explained in part by the histologic changes in the renal parenchyma.

Six male Beagles were inoculated with Ehrlichia canis. Transient proteinuria was confirmed during the acute phase of infection by serial determination of urinary protein-to-creatinine ratio. Peak urine protein loss, consisting principally of albumin, was observed 2.5 to 3.5 weeks after inoculation. Renal biopsy specimens were obtained before inoculation, during peak proteinuria, and 10 weeks after inoculation when proteinuria had resolved. Renal tissue was evaluated by use of light, immunofluorescent, and electron microscopy to correlate specific glomerular lesions with development of proteinuria. Histologic examination revealed perivenular and interstitial infiltrates of lymphocytes and plasma cells localized principally to the renal cortex. Glomerular lesions were minimal to absent. Immunofluorescent staining revealed moderate to marked deposition of anti-canine IgG and IgM in the glomerular tufts and mesangium. Depositions of anti-canine complement factor C3 were not observed. Immunofluorescent staining persisted 10 weeks after inoculation, despite resolution of proteinuria, and probably represented passive trapping of immunoglobulins. Ultrastructural examination revealed fusion of podocyte processes that coincided with development of proteinuria. Electron-dense deposits or changes in the basement membrane were not observed. Morphometric measurements of average podocyte process length and percentage of coverage of basement membrane by podocyte processes were used to quantify the degree of process fusion. Both measurements increased significantly (P < 0.05) during peak proteinuria, and returned to preinoculation values when proteinuria had resolved 10 weeks after E canis inoculation. These findings indicated possible minimal-change glomerulopathy, rather than immune-complex glomerulonephritis, during acute E canis infection and could explain transient proteinuria without histologic evidence of glomerular disease.

To determine the role of thromboxane A2 in the pathogenesis of experimentally induced immune complex glomerulonephritis, 12 concanavalin A-immunized Beagles were infused with 1 mg of concanavalin A via each renal artery and treated twice daily for 8 days with either 30 mg of CGS 12970/kg, PO, a specific thromboxane synthetase inhibitor, or placebo. The effect of treatment was assessed by measuring endogenous creatinine clearance and urine protein and eicosanoid excretion, and by evaluating changes in glomerular morphometric characteristics. On postinfusion day 8, urine protein, thromboxane B2, and 11-dehydro-thromboxane B2 excretion, glomerular epithelial crescent formation, and glomerular cell proliferation in the CGS 12970-treated dogs were significantly decreased when compared with values in the placebo-treated group. Differences were not observed in endogenous creatinine clearance, urine prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, or glomerular polymorphonuclear leukocyte infiltration between groups in this study. These findings suggest thromboxane A2 has a role in the development of immune complex glomerulonephritis and that thromboxane synthetase inhibition may be beneficial in attenuating some of the functional and histologic changes associated with immune complex glomerulonephritis.

Three methods of determining glomerular filtration rate (GFR) were performed in adult ferrets, 9 months to 7 years old. Endogenous creatinine clearance was determined, using serum and urine creatinine values obtained during 24- and 48-hour collection periods from 27 ferrets housed in metabolic cages. Creatinine and radiolabeled inulin were administered to 12 female ferrets by constant IV infusion during isoflurane-induced anesthesia. Serial 20-minute urine collections, together with serum samples obtained at the midpoint of urine collection, provided measures for clearance calculations of these substances. Mean +/- SD endogenous creatinine clearance in ferrets for metabolic cage collections was 2.50 +/- 0.93 ml/min/ kg of body weight. There were no significant differences between the 24- and 48-hour clearance rates. Mean inulin clearance was 3.02 +/- 1.78, and mean exogenous creatinine clearance was 3.32 +/- 2.16 ml/ min/kg. Analysis of variance, using least-squared means adjustment, did not yield any significant differences between inulin and exogenous creatinine clearance rates. Exogenous creatinine clearance-to-inulin clearance ratio was 0.99 +/- 0.46, and there was significant correlation between the 2 methods (r = 0.82, P = 0.0001). Significant body temperature effects on inulin or exogenous creatinine clearance were not found. Infused inulin clearance, the generally preferred method for GFR calculation in mammalian species, was significantly (P = 0.0069) higher in younger (3.65 ml/min/kg) vs older ferrets (2.29 ml/min/kg). Results of this study indicate that inulin clearance is an adequate measure of GFR in ferrets as it is in other species. Compared with inulin clearance, exogenous creatinine clearance also provides a reliable estimate of GFR in ferrets.

Twelve Beagles were inoculated with concanavalin A, and after a mean ninefold increase in antibody titer, 1 mg of concanavalin A was infused into each renal artery of each dog to induce in situ immune complex glomerulonephritis. Starting 4 weeks after renal arterial infusion, 6 dogs were treated orally 3 times daily with 30 mg of 3-methyl-2 (3 pyridyl)-1-indoleoctanoic acid (CGS 12970)/kg of body weight, a thromboxane synthetase inhibitor, and 6 dogs (control group) received a gelatin capsule 3 times daily. Endogenous creatinine clearance and 24-hour urinary excretion of protein and thromboxane B2 were determined for each dog prior to renal arterial infusion, at the initiation of treatment and at 2, 4, 6, and 8 weeks after initiation of treatment. In addition, methyoxy-(3)H inulin clearance was determined at initiation of treatment and 4 and 8 weeks later. Renal specimens were examined histologically at the initiation of treatment and 4 and 8 weeks later. Glomerular mononuclear profiles/micrometers(3) were determined from at least 10 equatorially sectioned glomeruli from each dog. Paired t tests were used to compare mean values at the various time points to the respective mean baseline value and 2-sample t tests were used to evaluate differences between treatment groups. At the start of treatment (4 weeks after renal arterial infusion of concanavalin A), histologic evaluation of renal specimens revealed glomerular epithelial crescent formation, mononuclear cell proliferation, and infiltration of neutrophils. Mononuclear cell profiles and urinary excretion of protein and thromboxane B2 were significantly increased, but endogenous creatinine clearance values were unchanged. Treatment with CGS 12970 did not affect endogenous creatinine clearance, methyoxy-(3)H inulin clearance, or glomeruli, however, CGS 12970 treatment significantly decreased urinary excretion of protein and thromboxane B2 when compared with values in the control group. These findings suggested that thromboxane has a role in the pathogenesis of established glomerulonephritis and that thromboxane synthetase inhibition treatment may be beneficial in dogs with established glomerulonephritis.