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Biomedical subjects

G F Grauer

Publications and source records attributed to G F Grauer.

At least 19 recordsLinked to original sources

Canine glomerulonephritis: new thoughts on proteinuria and treatment.

Glomerular disease in the dog is not only a common form of renal disease but also an important cause of chronic renal failure. The presence of immune complexes in glomerular capillary walls is a major cause of canine glomerular disease and is commonly referred to as glomerulonephritis. Leakage of plasma proteins, principally albumin, across the damaged glomerular capillary walls results in persistent proteinuria--the clinicopathological hallmark of glomerulonephritis. Recent evidence suggests that, in addition to being a marker of disease, persistent proteinuria is associated with progressive glomerular and tubulointerstitial lesions and loss of additional nephrons. Perhaps the best treatment for glomerulonephritis is the identification and correction of any underlying inflammatory, immune-mediated or neoplastic disease that results in the deposition or formation of glomerular immune complexes. In cases of idiopathic glomerulonephritis, angiotensin-converting enzyme inhibitors have been shown to decrease proteinuria and potentially slow disease progression.

Angiotensin-Converting Enzyme Inhibitors↗

Fluid therapy in acute and chronic renal failure.

Fluid therapy is one of the mainstays of treatment for renal failure, and rehydration is the primary goal. In those patients with ARF or "acute on chronic" decompensated CRF, induction of a diuresis to facilitate renal excretory function is important. Measurement of urine production in these patients helps guide fluid and electrolyte therapy. In oliguric renal failure, retention of water and electrolytes is likely, whereas in nonoliguric ARF as well as CRF, loss of water and electrolytes is the primary concern.

Acute Kidney Injury↗

Safety and efficacy of 4-methylpyrazole for treatment of suspected or confirmed ethylene glycol intoxication in dogs: 107 cases (1983-1995).

OBJECTIVE: To evaluate safety and efficacy of 4-methylpyrazole (4-MP) treatment in dogs and to determine clinical signs and outcome of, and clinicopathologic abnormalities in, dogs treated in early or late stages of ethylene glycol (EG) intoxication. DESIGN: Retrospective study. ANIMALS: 107 dogs. PROCEDURE: For dogs treated with 4-MP, 1 of 2 dosage regimens was usually used: 20 mg/kg of body weight, IV, initially, 15 mg/kg 17 hours later, and 5 mg/kg 25 and 36 hours after the initial dose, or 20 mg/kg, IV, initially, 15 mg/kg 12 and 24 hours later, and 5 mg/kg 36 hours after the initial dose. RESULTS: Neither adverse clinical signs nor clinicopathologic abnormalities were associated with the administration of 4-MP except in 1 dog, which developed tachypnea, gagging, excess salivation, and trembling after the second dose of 4-MP was given. Ethylene glycol intoxication was confirmed in 37 dogs. Of these, 21 were azotemic or became azotemic within 18 hours after admission, and only 1 of the 21 survived. All 16 dogs that did not become azotemic survived. Median time from EG ingestion to treatment with 4-MP was 5 hours (range, 2 to 8.5 hours) for dogs that were not azotemic at admission and 14.5 hours (range, 8.5 to 38 hours) for dogs that were azotemic at admission. CLINICAL IMPLICATIONS: 4-MP was a safe and effective treatment for EG intoxication when it was given before sufficient quantities of EG had been metabolized to induce renal failure. Dogs treated within 8 hours of EG ingestion had a good prognosis.

Acid-Base Equilibrium↗

Hospital-acquired acute renal failure in dogs: 29 cases (1983-1992).

OBJECTIVE: To assess factors associated with development of hospital-acquired acute renal failure (HARF) and to determine outcome of and prognostic indicators for dogs with HARF. DESIGN: Retrospective case series. ANIMALS: 29 dogs. RESULTS: The most common inciting causes for developments of HARF were exposure to a nephrotoxicant and advanced age. Mortality was 62%, and factors that contributed to mortality were age and initial urine output. Dogs > or = 7 years old and dogs that were initially oliguric had an odds ratio of mortality of 8.8 and 20, respectively. The effect of preexisting heart disease on mortality approached significance (P = 0.053). The magnitude of azotemia at the time of diagnosis was not related to the chance for survival. Dogs that died had a significantly higher initial anion gap and serum phosphorus concentration than did dogs that survived. We did not detect a relationship between cause of HARF and outcome (survived vs died or euthanatized). CLINICAL IMPLICATIONS: In most cases, HARF is associated with a poor outcome. Older dogs may be at increased risk for development of HARF, and once HARF has developed, have a greater chance of dying. Prognosis can not be determined on the magnitude of azotemia at the time of diagnosis or on the inciting cause of HARF.

Acid-Base Equilibrium↗

Prevention of acute renal failure.

Acute renal failure (ARF) induced by therapeutic agents that are nephrotoxic (e.g., gentamicin, cisplatin, amphotericin, and nonsteroidal anti-inflammatory drugs) or hypotension associated with anesthesia and surgery unfortunately occur with some regularity in small animal practice. Several clinical conditions have been identified that can increase the risk of hospital-acquired ARF in dogs. Recognition of these risk factors allows the clinician to assess the risk/benefit ratio for various drugs and/or procedures. Additionally, initiating protective measures and increasing the monitoring of renal function in those patients that require potentially harmful treatment may decrease the incidence of hospital-acquired ARF.

Animals↗

Effects of dietary n-3 fatty acid supplementation versus thromboxane synthetase inhibition on gentamicin-induced nephrotoxicosis in healthy male dogs.

OBJECTIVE: To evaluate the protective effects of dietary n-3 fatty acid supplementation versus treatment with a thromboxane synthetase inhibitor (TXSI) in dogs given high-dose gentamicin. DESIGN: Clinicopathologic and renal histopathologic changes induced by gentamicin (10 mg/kg of body weight, IM, q 8 h, for 8 days) were compared in dogs fed an n-3 fatty acid-supplemented diet containing a fatty acid ratio of 5.7:1 (n-6:n-3), dogs treated with CGS 12970 (a specific TXSI given at 30 mg/kg, PO, q 8 h, beginning 2 days prior to gentamicin administration), and control dogs. The TXSI-treated and control dogs were fed a diet with a fatty acid ratio of 51.5:1 (n-6:n-3). Both diets were fed beginning 42 days prior to and during the 8-day course of gentamicin administration. ANIMALS: Eighteen 6-month-old male Beagles, 6 in each group. RESULTS: After 8 days of gentamicin administration, differences existed among groups. Compared with n-3-supplemented and control dogs. TXSI-treated dogs had higher creatinine clearance. Both TXSI-treated and n-3-supplemented dogs had higher urinary prostaglandin E2 and E3 (PGE2/3) and 6-keto prostaglandin F1a (PGF1a) excretion, compared with control dogs. Urinary thromboxane B2 (TXB2) excretion was higher in n-3-supplemented and control dogs, compared with TXSI-treated dogs. Urine PGE2/3-to-TXB2 and PGF(in)-to-TXB2, ratios were increased in TXSI-treated dogs, compared with n-3-supplemented and control dogs, and these ratios were increased in n-3-supplemented dogs, compared with control dogs. In addition, TXSI-treated and n-3-supplemented dogs had lower urinary protein excretion, compared with control dogs. Proximal tubular necrosis was less severe in TXSI-treated dogs, compared with control dogs. CONCLUSION: Treatment with CGS 12970 prior to and during gentamicin administration prevented increases in urinary TXB2 excretion and reduced nephrotoxicosis. CLINICAL RELEVANCE: Increased renal production/excretion of thromboxane is important in the pathogenesis of gentamicin-induced nephrotoxicosis.

Animals↗

Effects of dietary protein conditioning on gentamicin pharmacokinetics in dogs.

Eighteen, six-month-old male Beagles with normal renal function were randomly divided into three groups of 6. Each group was fed a diet that was similar except for protein content (high = 26%, medium = 13% and low = 9%, all on an as fed basis) throughout the experimental period. After a 21 day dietary protein conditioning period (including a terminal 2 day testing period), gentamicin was administered at a dosage of 10 mg/kg q. 8 h for 8 days. The first dose on days 1 and 7 was administered i.v. and all others were given i.m. Pharmacokinetic parameters were determined using blood samples collected over an 8 h period following the i.v. dose on day 1. The elimination rate constant was calculated on days 1 and 7. The data best fit a two-compartment open model for all dogs on day 1. The volume of distribution was higher and the clearance greater in the high protein group compared to the other two groups. No difference was found in the rate of elimination between days 1 and 7 for the high protein group; however, in the medium and low protein groups the rate of elimination decreased over the 7 days of treatment. Therefore, high dietary protein prior to and during gentamicin administration induced faster gentamicin clearance and a larger volume of distribution and preserved the ability to eliminate gentamicin in dogs with normal renal function.

Animals↗

Effects of dietary protein conditioning on gentamicin-induced nephrotoxicosis in healthy male dogs.

Eighteen 6-month-old male Beagles with normal renal function were allotted at random to 3 groups of 6 dogs each. For 21 days, each group was fed a diet that was similar except for protein content (high protein, 27.3%; medium protein, 13.7%; and low protein, 9.4%). After the conditioning period, gentamicin was administered at a dosage of 10 mg/kg of body weight, IM, every 8 hours for 8 days, and the respective diet was continued. Clearance of endogenous creatinine, 24-hour urinary excretion of protein and enzymes (gamma-glutamyltransferase, and N-acetyl-beta-D-glucosaminidase, and fractional clearance of sodium and potassium (%) were determined before and after dietary protein conditioning and on days 2, 4, 6, and 8 of gentamicin administration. Additionally, trough serum gentamicin concentration was determined on days 2, 4, 6, and 8 of gentamicin administration. At the end of the study, all dogs were euthanatized; renal histologic features were graded, using a continuous ranking scale, and renal cortical gentamicin concentrations were measured. Data were ranked and analyzed, using a nonparametric equivalent of a two-way ANOVA; P < 0.05 was considered significant. After the dietary conditioning period (prior to gentamicin), dogs fed the high-protein diet had higher endogenous creatinine clearance and urinary excretion of protein, compared with dogs fed the low-protein diet. Differences existed among groups after 8 days of gentamicin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

Effects of a thromboxane synthetase inhibitor on established immune complex glomerulonephritis in dogs.

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-indolectanoic 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-3H 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/microns 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of low-dose aspirin and specific thromboxane synthetase inhibition on whole blood platelet aggregation and adenosine triphosphate secretion in healthy dogs.

Platelet aggregation and adenosine triphosphate (ATP) secretion in response to arachidonic acid (10 microM) or collagen (5 micrograms/ml) were compared in healthy, adult female Beagles treated with low-dosage aspirin (3.5 mg/kg of body weight, PO, q 12 h for 7 treatments) or with CGS 12970, a specific thromboxane synthetase inhibitor (10 mg/kg, PO, q 8 h for 10 treatments). Platelet aggregation was assessed in whole blood by use of an electrical impedance method. Baseline values obtained prior to treatment served as controls. Addition of arachidonic acid to blood from nontreated dogs resulted in significantly (P less than 0.001) increased impedance, but had no effect in blood from dogs treated with either aspirin or CGS 12970. Treatment with CGS 12970 or aspirin significantly (P less than 0.001) decreased platelet ATP secretion in response to arachidonic acid, compared with baseline values; however ATP secretion in aspirin-treated dogs was significantly (P less than 0.01) less than ATP secretion in CGS 12970-treated dogs. Differences in platelet aggregation were not observed between control dogs and aspirin- or CGS 12970-treated dogs in response to collagen as an aggregant, however, collagen-induced platelet ATP secretion was significantly (P less than 0.001) decreased in dogs treated with aspirin, compared with control values and values from dogs treated with CGS 12970. In dogs treated orally with 0.1, 0.2, 1.0, or 10 mg of CGS 12970/kg, dose-dependent inhibition of arachidonic acid-induced platelet aggregation was observed, with impedance changes not observed at the 10-mg/kg dosage and normal platelet aggregation associated with the 0.1-mg/kg dosage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Effects of thromboxane synthetase inhibition on immune complex glomerulonephritis.

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 histological changes associated with immune complex glomerulonephritis.

6-Ketoprostaglandin F1 alpha↗

Effects of a specific thromboxane synthetase inhibitor on thromboxane generation and excretion in healthy dogs.

A specific thromboxane synthetase inhibitor, 3-methyl-2 (3-pyridyl)-1-indoleoctanoic acid (CGS 12970) was administered orally to 6 healthy adult Beagles at a dosage of 30 mg/kg of body weight. Blood generation of thromboxane B2 and urinary excretion of thromboxane B2 were measured before and after administration of CGS 12970. Although 97 +/- 0.4% inhibition of thromboxane B2 generation was observed within 2 hours after a single dose of CGS 12970 was administered orally, an effect on urinary excretion of thromboxane B2 was not observed. Additionally, oral administration of 30 mg/kg every 12 hours resulted in 80 +/- 14% inhibition of thromboxane B2 generation but had no effect on urinary thromboxane B2 excretion.

Administration, Oral↗

Experimental Dirofilaria immitis-associated glomerulonephritis induced in part by in situ formation of immune complexes in the glomerular capillary wall.

Eight dogs were immunized with an aqueous-soluble extract of adult Dirofilaria immitis. Subsequent to at least 7-fold increases in antibody titer, the left renal artery of each dog was infused with 6 mg of D. immitis antigen. Fourteen days after infusion, the left kidney was compared to the right kidney and preinfusion biopsies. All dogs developed glomerular lesions in the left kidney characterized by 1 or more of the following: mesangial cell proliferation, neutrophil infiltration, increased periodic acid-Schiff-positive staining of the mesangium and glomerular basement membrane (GBM), fibrin deposition, and thickening of the GBM. Left kidney glomerular immunofluorescence was positive in 7 of the 8 dogs using polyclonal antisera for canine IgG and C3 in a linear or fine granular pattern. Ultrastructural lesions were present in the left kidney of all dogs and consisted of irregular GBM thickening, intramembranous and mesangial electron-dense deposits, and mesangial and endothelial cell proliferation. Antibodies directed against D. immitis antigen were demonstrated in all kidney eluates from the left kidney. The right kidneys of 3 of the dogs developed lesions; however, in comparison to the left kidney, the lesions in the right kidneys were inconsistent, mild, and focal. The histologic findings in the left kidney were similar to those observed in dogs with naturally occurring D. immitis infections. In sham-immunized control dogs, renal arterial infusion of D. immitis antigen did not cause consistent immune complex glomerulonephritis; however, antigen adherence to glomerular capillary walls was observed by immunofluorescent microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Renal lesions associated with Borrelia burgdorferi infection in a dog.

Borrelia burgdorferi infection was diagnosed serologically in a dog with lethargy, stiffness, and anorexia. Treatment with ampicillin and chloramphenicol did not alleviate the signs. Azotemia, proteinuria, cylindruria, pyuria, and hematuria developed over a 3-month period. Antibody titer for B burgdorferi remained high (1:8,192) during this time. Renal histopathologic findings included severe, chronic, diffuse, membranoproliferative glomerulonephritis and moderate chronic, multifocal, interstitial nephritis. Borrelia burgdorferi organisms were identified in renal tissue and in urine by results of immunofluorescent studies and bacteriologic culture, respectively.

Animals↗

Parasite excretory-secretory antigen and antibody to excretory-secretory antigen in body fluids and kidney tissue of Dirofilaria immitis infected dogs.

Excretory-secretory (ES) antigens of adult Dirofilaria immitis were detected by enzyme-linked immunosorbent assay (ELISA) in serum and urine from each of 12 experimentally infected dogs. Excretory-secretory antigens in serum were first detected 154 days postinfection. Serum antibodies directed against parasite ES antigens were detected by ELISA in all dogs. Kidney tissue elution studies were performed in 10 dogs, and antibody and parasite ES antigens were demonstrated in each case. Antibody or parasite antigen was not detected in serum, urine, or kidney eluates from uninfected dogs. At peak concentrations of the ES antigens in serum, there were correlations with the number of adult D. immitis present in the dogs (r2 = 23.8, P less than 0.05) and with the antigen concentration in kidney eluates (r2 = 73.5, P less than 0.001). Peak serum antibody concentrations were not correlated with either the number of adult worms or the antibody concentrations in kidney eluates. This study suggests that detection of parasite antigens in urine may be an important diagnostic aid. In addition, the correlation between the concentration of D. immitis ES antigens in kidney tissue and in serum without a similar correlation between serum and kidney antibody concentrations suggests that D. immitis ES antigens adhere to kidney tissue.

Animals↗

Renal microcirculatory and correlated histologic changes associated with dirofilariasis in dogs.

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.

Animals↗

Reversal of ethylene glycol-induced nephrotoxicosis in a dog.

Ethylene glycol-induced nephrotoxicosis was diagnosed in a dog with acute renal failure. Histologically, the dog had proximal tubular degeneration and necrosis, intraluminal calcium oxalate crystals, generally intact tubular basement membranes, and evidence of tubular regeneration. After 20 days of peritoneal dialysis and diuresis, renal function was adequate to maintain homeostasis without supportive care. Nine weeks after onset of the ethylene glycol-induced renal failure, the dog's kidneys were histologically and functionally normal.

Acute Kidney Injury↗