Advanced therapeutic approaches for the management of uraemia--'the met and unmet needs'.
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Biomedical subjects
Publications and source records attributed to L D Cowgill.
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OBJECTIVE: To evaluate quantification of the amount of carbamylated hemoglobin (CarbHb), using capillary electrophoresis (CE) and a new dynamic capillary coating system to separate hemoglobin derivatives, and to assess the use of CarbHb amounts to evaluate long-term urea exposure and differential diagnoses of azotemia in dogs. ANIMALS: 8 dogs with renal failure, 2 dogs with diabetes mellitus, and 7 control dogs. PROCEDURE: Optimal analytic conditions for separation of CarbHb and other hemoglobin derivatives in blood samples obtained from dogs were determined, using a commercial analysis system developed for the detection of glycohemoglobin Hb A1c (GlycHb) in human blood samples. Relative content of hemoglobin derivatives in blood from 10 dogs with renal failure or endocrine diseases were compared with values for 7 dogs without renal or endocrine diseases. RESULTS: Satisfactory resolution of hemoglobin derivatives was obtained, which permitted identification and quantitation of the amount of CarbHb as a percentage of the total amount of hemoglobin. Normal or increased amounts of GlycHb did not interfere with CarbHb analysis. Dogs with chronic renal failure had considerably higher peak amounts of CarbHb than dogs with acute renal failure, a dog with chronic renal failure that was treated by use of hemodialysis, or dogs without renal disease. CONCLUSIONS AND CLINICAL RELEVANCE: Amounts of CarbHb in blood samples obtained from dogs can be readily quantified by use of capillary electrophoresis. Assessment of the amount of CarbHb can be used to facilitate evaluation of the cause of azotemia in dogs.
OBJECTIVE: To characterize serologic and clinical features and outcome of dogs with leptospirosis that were treated conservatively (i.e., medical management alone) or with hemodialysis. DESIGN: Retrospective study. ANIMALS: 36 dogs with leptospirosis. PROCEDURE: History; results of physical examinations, ultrasonography, and serologic, hematologic, and serum biochemical analyses; time to resolution of azotemia; and outcome were obtained from medical records. Dogs were treated conservatively (n = 22) or with hemodialysis (14). RESULTS: Between 1990 and 1998, amount of rainfall was positively correlated with number of cases of leptospirosis identified per year. Serum antibodies against 6 Leptospira serovars were measured, and titers were highest to Leptospira pomona in 16 (44%) dogs, L bratislava in 9 (25%) dogs, and L hardjo in 1 (3%) dog. Eight (22%) dogs had equally high titers to L pomona and L bratislava, 1 (3%) had equally high titers to L grippotyphosa and L canicola, and 1 (3%) had high titers to L grippotyphosa, L pomona, L canicola, and L bratislava. During initial evaluation, all dogs were azotemic. Thirty (83%) dogs survived, including 12 of 14 (86%) dogs treated with hemodialysis and 18 of 22 (82%) treated conservatively. Serum creatinine concentration was similar in both groups after resolution of clinical signs. CONCLUSIONS AND CLINICAL RELEVANCE: Infection with L pomona and L bratislava was recognized as a cause of leptospirosis in dogs, and resulted in development of acute renal failure with various degrees of azotemia. Prognosis for dogs with mild to moderate azotemia was good with conservative treatment, whereas treatment with hemodialysis appeared to improve prognosis for dogs with severe azotemia.
OBJECTIVE: To characterize the effect of maintenance hemodialysis on plasma amino acid concentrations and to quantitate free amino acid losses into the dialysate during hemodialysis in healthy dogs. ANIMALS: 8 healthy adult dogs. PROCEDURE: Five dogs received hemodialysis treatments 3 times per week for 4 weeks. Plasma amino acid concentrations were evaluated once per week for 4 weeks in each of the 5 dogs prior to hemodialysis (time 0), 90 minutes during hemodialysis, and immediately after hemodialysis (180 minutes). Total free amino acid concentrations and plasma amino acid concentrations (time 0, 90 minutes, and 180 minutes) in the dialysate were evaluated in 3 dogs that received 1 hemodialysis treatment. RESULTS: Significant time versus week interactions with any plasma amino acid were not detected; however, significant decreases in all plasma amino acid concentrations measured were detected at the midpoint of dialysis (46 +/- 2%) and at the end of each dialysis session (38 +/- 2%). Mean (+/- SEM) total free amino acid loss into the dialysate was 2.7 +/- 0.2 g or 0.12 g/kg of body weight. CONCLUSIONS AND CLINICAL RELEVANCE: Hemodialysis is associated with significant alterations in plasma amino acid concentrations and loss of free amino acids into the dialysate. Loss of amino acids into the dialysate, coupled with protein calorie malnutrition in uremic patients, may contribute to depletion of amino acid stores.
OBJECTIVE: To characterize potential changes in preprandial plasma amino acid concentrations in cats with naturally acquired chronic renal failure (CRF), compared with healthy cats, and to assess potential effects of the severity of renal failure on plasma amino acid concentrations in these cats. ANIMALS: 62 adult cats. PROCEDURE: Preprandial plasma amino acid concentrations were evaluated in 38 cats with mild, moderate, or severe CRF and in 24 apparently healthy cats. Effects of severity of renal failure, amount of dietary protein, degree of weight loss, appetite, and body condition on plasma amino acid profiles were evaluated. RESULTS: Cats with various stages of CRF had significantly (P< 0.05) decreased plasma concentrations of o-hydroxyproline, glutamate, proline, glycine, alanine, tyrosine, tryptophan, and arginine, and significantly increased plasma concentrations of asparagine, citrulline, ornithine, 1-methylhistidine, and 3-methylhistidine. Significant (P < 0.05) alterations in amino acid concentrations also were identified when cats with CRF were grouped by appetite or severity of renal disease. Amount of dietary protein, body condition, or degree of weight loss had no significant effect on plasma amino acid concentrations. CONCLUSIONS: Compared with those in healthy cats, preprandial plasma amino acid profiles in cats with mild, moderate, or severe CRF are abnormal. CLINICAL RELEVANCE: Despite frequency of altered plasma amino acid concentrations in cats with CRF, the magnitude of these changes is mild and of little clinical relevance. Short-term use of a commercial protein-restricted diet has no deleterious effects on plasma amino acid concentrations.
OBJECTIVE: To determine the prevalence of hypergastrinemia in cats with naturally developing chronic renal failure (CRF) and the correlation between gastrin concentration in plasma and severity of CRF. DESIGN: Cohort study. ANIMALS: 30 cats with naturally developing CRF and 12 clinically normal control cats. PROCEDURE: Gastrin concentrations in plasma were determined by double-antibody radioimmunoassay of blood samples obtained from cats after food was withheld 8 hours. Concentrations were compared, using a nonparametric Kruskal-Wallis ANOVA. RESULTS: 18 cats with CRF had high gastrin concentrations (median, 45 pg/ml; range, < 18 to > 1,333 pg/ml), compared with those for control cats (< 18 pg/ml). Prevalence of hypergastrinemia increased with severity of renal insufficiency. Three of 9 cats with mild CRF, 6 of 11 cats with moderate CRF, and 9 of 10 cats with severe CRF had high gastrin concentrations. Gastrin concentrations were significantly different between control cats and cats with CRF, regardless of disease severity. CLINICAL IMPLICATIONS: The potential role of high concentrations of gastrin on gastric hyperacidity, uremic gastritis, bleeding from the gastrointestinal tract, and associated clinical signs of hypergastrinemia (e.g., anorexia and vomiting) may justify use of histamine2-receptor antagonists or proton pump inhibitors to suppress gastric acid secretion in cats with CRF that have these clinical signs.
OBJECTIVE: To test efficacy and safety of recombinant human erythropoietin (r-HuEPO) administration in dogs and cats with naturally developing chronic renal failure. DESIGN: Case series. ANIMALS: 6 client-owned dogs and 11 client-owned cats with chronic renal failure. PROCEDURES: r-HuEPO was administered intravenously or subcutaneously. Erythropoietic effects were monitored by determining CBC, performing cytologic examination of bone marrow aspirates, and measuring serum iron concentration before and during treatment. Development of adverse effects was monitored by performing sequential clinical assessments, CBC, and serum biochemical tests and by measuring indirect blood pressure and anti-r-HuEPO antibody titers. RESULTS: Administration of r-HuEPO increased RBC and reticulocyte counts, hemoglobin concentration, and Hct comparably in dogs and cats. Assessments of clinical well-being, including appetite, energy, weight gain, alertness, strength, and playfulness, were improved variably. Adverse effects, including anemia, anti-r-HuEPO antibody production, seizures, systemic hypertension, and iron deficiency, were demonstrated inconsistently in dogs and cats. CLINICAL IMPLICATIONS: Anemia contributes to clinical manifestations of chronic renal failure in dogs and cats. Administration of r-HuEPO has the potential to resolve anemia and improve clinical well-being. However, its administration poses risks of antibody production and adverse effects associated with correction of RBC mass. Use of r-HuEPO in dogs and cats requires conscientious assessment of risks and benefits until homologous forms of erythropoietin are available.
OBJECTIVE: To compare blood pressure and heart rate measurements performed in a veterinary clinic to similar measurements performed in a dog's home. DESIGN: Prospective study. ANIMALS: 14 client-owned, clinically normal dogs. PROCEDURE: Sequential blood pressure and heart rate measurements were recorded from the metatarsus and metacarpus of conscious dogs by indirect oscillometry. Measurements were performed in the dogs' homes and were repeated in a veterinary clinic. Blood pressures and heart rate were derived from 7 serial estimates over 8 to 10 minutes. Statistical differences between the home and clinic and between recording sites were calculated. RESULTS: Systolic, diastolic, and mean blood pressure and heart rate measurements obtained from the metatarsus and metacarpus in the dogs' homes were significantly lower than measurements from the metatarsus in the clinic, but were similar to measurements from the metacarpus in the clinic. Significant differences were not found between blood pressure measurements from the metatarsus and metacarpus in the dogs' homes, but systolic and mean blood pressure and heart rate measurements from the metacarpus in the clinic were significantly lower than measurements from the metatarsus. Whereas all dogs had normal blood pressure in their homes, 5 of 14 dogs had transient hypertension (systolic pressure > 165 mm of Hg or diastolic pressure > 95 mm of Hg) in the clinic. CLINICAL IMPLICATIONS: Blood pressure and heart rate measurements obtained in the clinic initially overestimate comparable measurements in a dog's home. The differences are best explained by transient autonomic responses to the stress of the clinic. Blood pressure must be measured by use of standardized techniques on dogs acclimated to the clinic environment.
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OBJECTIVE: To determine usefulness of carbamylated hemoglobin (CarHb) concentration for differentiation of acute renal failure (ARF) from chronic renal failure (CRF) in dogs. SAMPLE POPULATION: Samples from dogs with ARF or CRF and from nonazotemic control dogs. PROCEDURE: CarHb concentration was determined in heparinized blood samples by measuring the micrograms of valine hydantoin (VH) per gram of hemoglobin (Hb), using a high-performance liquid chromatography assay, in which carbamyl valine is converted to VH via acid hydrolysis. RESULTS: CarHb concentration was significantly higher in dogs with ARF and CRF, compared with values in control dogs (ARF vs control, P < 0.05; CRF vs control, P < 0.001). Furthermore, CarHb concentration was significantly (P < 0.001) higher in dogs with CRF, compared with that in dogs with ARF. Carbamylated hemoglobin concentration did not correlate with serum urea nitrogen or creatinine concentration. Using a cutoff value of 100 micrograms of VH/g of Hb, the sensitivity and specificity of CarHb concentration for differentiating ARF from CRF was 96.1 and 84.2%, respectively. CONCLUSIONS: CarHb concentration was useful in the differentiation of ARF from CRF in the dogs of this study. CLINICAL RELEVANCE: CarHb concentration may be used to increase the accuracy of identifying ARF, so that early, aggressive management can be instituted, thereby increasing the chance of recovery.
OBJECTIVE: To determine prevalence and severity of systemic arterial hypertension and proteinuria in dogs with naturally developing hyperadrenocorticism and to determine whether these abnormalities resolve with adequate management of the disease. DESIGN: Case series and cohort study. ANIMALS: 77 dogs with naturally developing hyper-adrenocorticism examined once; 15 dogs examined before and after treatment. RESULTS: Among dogs examined only once, hypertension was diagnosed in 21 of 26 dogs with untreated pituitary-dependent hyperadrenocorticism (PDH), 17 of 21 with inadequately controlled PDH, 8 of 16 with well-controlled PDH, 10 of 10 with an untreated adrenocortical tumor, and 0 of 4 that had undergone adrenalectomy because of an adrenocortical tumor. Untreated dogs and dogs with inadequately controlled PDH had significantly higher blood pressures than did other dogs. Proteinuria was documented in 12 of 26 dogs with untreated PDH, 5 of 16 with inadequately controlled PDH, 3 of 14 with well-controlled PDH, 5 of 8 with an untreated adrenocortical tumor, and 1 of 3 that had undergone adrenalectomy. Dogs with untreated PDH and dogs with an untreated adrenocortical tumor had higher urine protein/creatinine ratios than did dogs with well-controlled PDH. Among dogs evaluated before and after treatment, blood pressure and urine protein/creatinine ratio did not change in 8 dogs with inadequately controlled hyperadrenocorticism, but decreased in 7 dogs with well-controlled disease. CLINICAL IMPLICATIONS: Results suggest that systemic hypertension and proteinuria are common in dogs with untreated hyperadrenocorticism and that successful treatment of hyperadrenocorticism will result in resolution of these abnormalities in many, but not all, dogs.
OBJECTIVE: To describe 7 cases of acute postoperative azotemia in dogs and to examine by use of a case-control study the possible association between this complication and administration of nafcillin. DESIGN: Retrospective and case-control study. ANIMALS: 7 case dogs and 28 matched control dogs. PROCEDURE: Cases of acute renal failure or acute renal insufficiency were identified by retrospective study of records of dogs treated between July 1, 1992, and Feb 28, 1995, and from information received from a practitioner. A random sample of records of dogs undergoing invasive procedures between Dec 1, 1992, and Nov 30, 1993, was examined to determine the prevalence of nafcillin use. Each case dog was matched with 4 control dogs, and data were subjected to logistic regression analysis, employing exact conditional inference on the parameter estimates. RESULTS: Case dogs were between 1 and 9 years old and weighed between 21 and 60 kg. Preoperatively, none of the dogs had a history of renal disease, and BUN concentrations, hematocrit, and plasma protein concentrations were within reference ranges. Postoperatively, each dog became azotemic and had clinical signs consistent with uremia. Hyponatremia was recorded in 6 case dogs. One dog did not respond to treatment and was euthanatized. Two dogs had persistent isosthenuria, and 4 dogs recovered. Nafcillin was used in approximately 502 of 2,184 (23%) dogs that underwent invasive procedures between Dec 1, 1992, and Nov 30, 1993. The use of nafcillin ceased on Nov 30, 1993, and no further cases were recorded in the following 15 months. In the case-control study, the only factor that was significantly associated with the occurrence of acute postoperative azotemia was administration of nafcillin. CLINICAL IMPLICATIONS: Intraoperative use of nafcillin maybe associated with development of acute postoperative azotemia in dogs.
Hemodialysis is a technically sophisticated therapy used to remove accumulated uremia toxins and correct the electrolyte, hydrogen ion, and fluid imbalances associated with renal failure. Hemodialysis is indicated when the morbidity or potential mortality from either acute or chronic renal failure cannot be alleviated by conventional therapies. Additionally, it is useful for the rapid removal of excessive fluid loads associated with congestive heart failure or iatrogenic fluid administration and the elimination of dialyzable poisons like ethylene glycol. The requirements for hemodialysis include repeated access to the vasculature, an artificial kidney, and a dialysis delivery system. Technologic advancements in all these requirements make the delivery of hemodialysis feasible, effective, and safe for both dogs and cats. To date, the limitation of facilities offering dialytic therapy has restricted its use in uremic animals but current improvements in dialysis techniques and the increased sophistication of specialty practice make hemodialysis a realistic adjunct to the conservative management of uremia in veterinary medicine.
Feline dysautonomia was diagnosed in a 2-year-old cat with a history of regurgitation, constipation, mydriasis, and dry eyes. The diagnosis of parasympathetic and sympathetic failure was confirmed by abnormal physiologic autonomic function tests and decreased urinary catecholamine measurements. Despite intensive supportive care, the cat failed to improve and was euthanatized 70 days after the onset of illness. Feline dysautonomia is rarely reported in the United States, and the cat had no history of travel to a country where the disease is more prevalent.
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Acute renal failure in a 4-day-old foal secondary to oxytetracycline toxicosis was treated by hemodialysis. Oxytetracycline had been administrered as treatment for forelimb flexor tendon contracture. Conservtive treatment with fluids, furosemide, and dopamine partially alleviated serum electrolyte concentration imbalances, but was ineffective in promoting diuresis or decreasing azotemia. Three hemodialysis treatments over 4 days were administered, after which the clinical appearance of the foal improved, and biochemical and electrolyte values returned to within reference ranges. The nephrotoxic potential of oxytetracycline should be considered prior to its administration. Hemodialysis may be a treatment option in management of acute renal failure in foals that are nonresponsive to conservative medical treatment.