The Use of Darbepoetin to Stimulate Erythropoiesis in the Treatment of Anemia of Chronic Kidney Disease in Dogs.

BACKGROUND: Darbepoetin alfa (darbepoetin) is an erythropoiesis-stimulating agent used for the treatment of anemia secondary to chronic kidney disease (CKD) in dogs, but reports describing response are lacking. HYPOTHESIS/OBJECTIVES: To evaluate the effectiveness of darbepoetin in dogs with anemia secondary to CKD, dosing protocols, and adverse events. ANIMALS: Thirty-three client-owned dogs with naturally occurring CKD, including 26 with comorbidities. METHODS: Multi-institutional retrospective study. RESULTS: The median starting dosage and highest dosage of darbepoetin administered were 0.5 and 0.8 µg/kg SC once weekly, respectively. Response to treatment was defined as achieving a packed cell volume (PCV) ≥30% or an increase in PCV ≥10%. Twenty-eight of 33 dogs (85%) achieved a PCV ≥30% and 22 of 33 (67%) dogs achieved an increase in PCV ≥10%. Median time to achieve a PCV ≥30% was 29 days. A higher starting dosage was associated with achieving an increase in PCV ≥10% (P = .01). No dog sustained a response at a dosing interval >q21d. Potential adverse events included increased blood pressure requiring treatment (n = 12), seizures (n = 5), vomiting (n = 3), diarrhea (n = 3), and possible pure red cell aplasia (PRCA) (n = 2). CONCLUSIONS AND CLINICAL IMPORTANCE: Darbepoetin, when combined with treatment of comorbidities, is an effective treatment for anemia secondary to CKD in dogs. A dosing interval >q21d was ineffective at maintaining a response to treatment. PRCA was a possible adverse event in 2 of 33 dogs (6%).

The pharmacokinetics of intravenous fenoldopam in healthy, awake cats.

Fenoldopam is a selective dopamine-1 receptor agonist that improves diuresis by increasing renal blood flow and perfusion and causing peripheral vasodilation. Fenoldopam has been shown to induce diuresis and be well-tolerated in healthy cats. It is used clinically in cats with oliguric kidney injury at doses extrapolated from human medicine and canine studies. The pharmacokinetics in healthy beagle dogs has been reported; however, pharmacokinetic data in cats are lacking. The goal of this study was to determine pharmacokinetic data for healthy, awake cats receiving an infusion of fenoldopam. Six healthy, awake, client-owned cats aged 2-6 years old received a 120-min constant rate infusion of fenoldopam at 0.8 µg/kg/min followed by a 20-min washout period. Ascorbate stabilized plasma samples were collected during and after the infusion for the measurement of fenoldopam concentration by HPLC with mass spectrometry detection. This study showed that the geometric mean of the volume of distribution, clearance, and half-life (198 mL/kg, 46 mL/kg/min, and 3.0 mins) is similar to pharmacokinetic parameters for humans. No adverse events were noted. Fenoldopam at a constant rate infusion of 0.8 µg/kg per min was well tolerated in healthy cats. Based on the results, further evaluation of fenoldopam in cats with kidney disease is recommended.

Consensus recommendations for immunosuppressive treatment of dogs with glomerular disease based on established pathology.

The purpose of this report was to provide consensus recommendations for the use of immunosuppressive therapy in dogs with active glomerular diseases. Recommendations were developed based on comprehensive review of relevant literature on immunosuppressive therapy of glomerular disease in dogs and humans, contemporary expert opinion, and anecdotal experience in dogs with glomerular disease treated with immunosuppression. Recommendations were subsequently validated by a formal consensus methodology. The Study Group recommends empirical application of immunosuppressive therapy for dogs with severe, persistent, or progressive glomerular disease in which there is evidence of an active immune-mediated pathogenesis on kidney biopsy and no identified contraindication to immunosuppressive therapy. The most compelling evidence supporting active immune-mediated mechanisms includes electron-dense deposits identified with transmission electron microscopic examination and unequivocal immunofluorescent staining in the glomeruli. For diseases associated with profound proteinuria, attendant hypoalbuminemia, nephrotic syndrome, or rapidly progressive azotemia, single drug or combination therapy consisting of rapidly acting immunosuppressive drugs is recommended. The Study Group recommends mycophenolate alone or in combination with prednisolone. To minimize the adverse effects, glucocorticoids should not be used as a sole treatment, and when used concurrently with mycophenolate, glucocorticoids should be tapered as quickly as possible. For stable or slowly progressive glomerular diseases, the Study Group recommends mycophenolate or chlorambucil alone or in combination with azathioprine on alternating days. Therapeutic effectiveness should be assessed serially by changes in proteinuria, renal function, and serum albumin concentration. In the absence of overt adverse effects, at least 8 weeks of the rapidly acting nonsteroidal drug therapy and 8-12 weeks of slowly acting drug therapy should be provided before altering or abandoning an immunosuppressive trial.

Preliminary pharmacokinetics and cardiovascular effects of fenoldopam continuous rate infusion in six healthy dogs.

Fenoldopam is a selective dopamine-1 receptor agonist that causes peripheral arterial vasodilation, increased renal blood flow, and diuresis. Enthusiasm exists for the use of fenoldopam in nonpolyuric kidney injury in dogs, although pharmacokinetic data are lacking. The purpose of this study was to collect basic pharmacokinetic and hemodynamic effect data for fenoldopam when administered to healthy awake dogs. Six healthy, awake beagles were given a 180-min fenoldopam constant rate infusion at 0.8 µg/kg per minute followed by a 120-min washout period. Citrated blood was collected during and after infusion for the measurement of plasma fenoldopam concentration by HPLC with mass spectrometry. Heart rate and indirect systolic blood pressure were concurrently measured. Mean ± SD, steady-state plasma fenoldopam concentrations of 20 ± 17 ng/mL were achieved within 10 min of starting the infusion. Area under the plasma concentration-time curve was 3678 ± 3030 ng/mL · min, and plasma clearance was 66 ± 43 mL/min per kg. Elimination was rapidly achieved in all dogs. Heart rate and systolic blood pressure were unaffected by the fenoldopam infusion. Based on the results of this study, further evaluation of the effects of fenoldopam in dogs at differing doses and in dogs with clinical conditions such as acute nonpolyuric kidney injury is warranted.

Peritoneal dialysis in cats with acute kidney injury: 22 cases (2001-2006).

BACKGROUND: Peritoneal dialysis (PD) has been described for use in animals with acute kidney injury refractory to fluid therapy. However, no study has examined the use of PD in a large group of cats. HYPOTHESIS: PD is an important adjunctive therapy to treat acute kidney injury in cats. ANIMALS: The medical records of 22 cats with acute kidney injury that had received PD were examined. Animals were excluded if acute uremia was a result of postrenal causes such as uroabdomen or urethral obstruction. METHODS: Medical records were reviewed for the following: indication for PD, outcome, number of cycles performed, survival time, and predialysis and postdialysis results for blood urea nitrogen (BUN), creatinine, potassium, chloride, sodium, phosphorus, total protein, and albumin concentrations, and urine output. RESULTS: Indications for PD include acute-on-chronic kidney injury, acute kidney injury caused by toxins, bilateral ureteroliths, bilateral ureteral ligation as a complication of ovariohysterectomy, and unknown causes. The median survival time for all cats on PD was 4 days, although the median survival time for the cats that were discharged was 774 days. The most common complications were dialysate retention and sequestration of dialysate SC. There was a significant (P < .05) decrease between predialysis and postdialysis results for BUN, creatinine, potassium, phosphorus, total protein, and albumin concentrations. There was a significant (P < .05) difference in survival times between sexes. CONCLUSIONS AND CLINICAL IMPORTANCE: PD is an effective option for treatment of cats with acute kidney injury refractory to fluid therapy.

Strategies for management of acute renal failure.

Acute renal failure (ARF) is often defined as the sudden inability of the kidneys to regulate water and solute balance. ARF may be more broadly defined as rapid deterioration of renal function resulting in the accumulation of nitrogenous wastes such as urea and creatinine. Clinically, oliguria is defined as urine flow of less than 2 mL/kg/h and anuria has no measurable urine production. In animals, the most common cause of ARF is nephrotoxicity; ischemia ranks second, with interstitial and glomerular diseases following.

Ultrasonography of the normal feline pancreas and associated anatomic landmarks: a prospective study of 20 cats.

The sonographic appearance of the feline pancreas and associated anatomic landmarks including the pancreatic duct, duodenum, duodenal papilla, portal vein, and gastric lymph node were evaluated in 20 healthy, awake cats. The pancreas appeared nearly isoechoic to surrounding mesenteric tissues, isoechoic to slightly hyperechoic to adjacent liver lobes, and hypoechoic to the spleen. The mean thickness measurements for the right pancreatic lobe, body, and left pancreatic lobe were 4.5 mm (range 2.8-5.9), 6.6 mm (range 4.7-9.5), and 5.4 mm (range 3.4-9.0), respectively. The pancreatic duct was consistently visualized in the left pancreatic lobe and had a mean thickness of 0.8 mm (range 0.5-1.3). It could be differentiated from the pancreatic vessel, by its central location, and the duct's lack of Doppler flow signal. The duodenum was used as a landmark to identify the right lobe of the pancreas. The mean duodenal wall thickness measurement was 2.8 mm (range 2.1-3.8) in sagittal section, and 3.0 mm (range 2.2-4.4) in transverse section. The duodenal papilla was identified in 4 of 20 cats. It ranged in size from 2.9 to 5.5 mm in width, and had a maximum height of 4.0 mm in transverse section. The portal vein was used as a consistent anatomic landmark for identification of the left lobe and body of the pancreas. The mean diameter of the portal vein at the level where the pancreatic body joins the left pancreatic lobe was 4.3 mm (range 2.7-5.9) when viewed in sagittal section, and 4.5 mm (range 3.6-6.1) in transverse section. The gastric lymph node was identified cranial and ventromedial to the pyloroduodenal angle in 6 of 20 cats. It had an asymmetrical shape with a larger caudal pole in five of the six cats. The largest dimensions of the gastric lymph node were 10 mm in length, and 6 mm in width for the larger caudal pole, and 5.1 mm in width for the smaller cranial pole.

Peritoneal dialysis in emergency and critical care medicine.

Peritoneal dialysis is a technique that has been used to treat acute renal failure in humans since 1923. Peritoneal dialysis is used in people to manage acute and chronic renal failure, as well as to remove dialyzable toxins (ethylene glycol, barbiturates, and ethanol), reduce severe metabolic disturbances, and for the treatment of peritonitis, pancreatitis, uroabdomen, hypothermia, and fluid overload. In veterinary medicine, acute renal failure is the prevailing indication for dialysis. This report will discuss the pathophysiology of peritoneal dialysis, indications, and contraindications. Catheter selection and placement will be reviewed. Types of dialysate solution will be discussed and the protocol established for instituting peritoneal dialysis. The report will conclude with a discussion of potential complications and methods to minimize them.

Familial glomerulonephropathy in a litter of beagles.

Membranoproliferative glomerulonephropathy was diagnosed in 5 of 7 adult Beagles from the same litter. Dogs were raised in more than 1 area of the United States. One died without evidence of renal disease when it was 3 years old. At 8 years of age, 2 dogs developed signs of uremia, including polyuria, polydipsia, and infrequent episodes of anorexia and vomiting. Serum biochemical variables and urine specific gravity values were consistent with renal azotemia. Both dogs had proteinuria. Although healthy, 3 of the 4 remaining Beagles had proteinuria. Of these 3, only 1 was azotemic. Membranoproliferative glomerulonephritis was diagnosed on the basis of results of histologic examination of renal biopsy specimens from 4 of the dogs. Electron microscopy performed on 3 of the renal biopsy specimens revealed identical lesions, consisting of an extremely thickened glomerular basement membrane with multilaminar splitting. Immunoglobulin or amyloid deposits were not detected. On the basis of similar clinicopathologic abnormalities, common genetic background, and identical histopathologic and electron microscopic findings, familial renal disease was diagnosed. Additional studies involving other related Beagles are needed to identify the hereditary nature of membranoproliferative glomerulonephropathy in Beagles.

Management of the uncomplicated canine diabetic.

Managing the uncomplicated canine diabetic may still be a challenging endeavor. Client education is the most important treatment to provide. The client must understand the technique of drug handling and administration, the importance of diet in treating the animal, how to handle an emergency situation, and, most importantly, the disease itself. The clinician must realize that although "tight" glycemic control is the optimal goal; the reality is often a compromise of mild hyperglycemia with resolution of clinical signs. When regulation cannot be maintained it is necessary to investigate the causes of insulin resistance.

Use of synthetic prostaglandin E1 (misoprostol) for prevention of aspirin-induced gastroduodenal ulceration in arthritic dogs.

A randomized, double-blind, controlled study was performed with 18 arthritic dogs administered aspirin (25 mg/kg of body weight, PO, q 8 h) and excipient (control group) or aspirin and misoprostol (100 micrograms, PO, q 8 h). Dogs in the misoprostol (n = 10) and control (n = 8) groups were primarily compared by use of sequential gastroduodenoscopy, changes in PCV, and prevalence of clinical signs of gastrointestinal disturbance over a 14-day treatment period. The misoprostol/aspirin-treated group had significantly (P < 0.05) less gastroduodenal hemorrhage and ulceration and a significantly (P < 0.05) lower prevalence of vomiting than did the control group.

Plasma disappearance of creatinine as a renal function test in the dog.

The serum concentration of creatinine at 120 minutes (SC120) after intravenous injection of 88 mg kg-1 of creatinine, the plasma half-life (t1/2) and the plasma clearance of creatinine (PCC) were evaluated as renal function tests in 30 healthy adult dogs and six adult dogs with known or suspected renal disease. The mean SC120 in the normal dog was 0.31 +/- 0.08 mmol litre-1 and in the clinical cases 0.71 +/- 0.19 mmol litre-1. The correlation coefficients between SC120 and renal creatinine clearance (RCC) for the normal dogs and the clinical cases were -0.76 and -0.69, respectively. At 120 minutes after injection, 95 per cent of normal dogs would be predicted to have a serum creatinine concentration below 0.46 mmol litre-1. The mean plasma t1/2 of creatinine for the normal dogs was 107.7 +/- 17.96 minutes, while the clinical cases had a wide range of values (148.8 to 620.1 minutes). Plasma t1/2 of creatinine was correlated with RCC for both the normal dogs and the clinical cases (r = -0.55, r = -0.91, respectively). The mean PCC for the normal dogs was 7.42 +/- 2.22 ml min-1 kg-1 (range 4.95 to 13.28 ml min-1 kg-1). There was a good correlation between RCC and PCC (r = 0.7). The PCC for the clinical cases ranged from 0.76 to 3.37 ml min-1 kg-1. The correlation between RCC and PCC was significant (r = 0.91). Thus SC120, t1/2 and PCC may be useful methods of assessing renal function in dogs with renal impairment insufficient to cause azotaemia.

Ketoconazole therapy in a dog with systemic cryptococcosis.

A 2-year-old dog had bilateral chorioretinitis and a cough. Systemic cryptococcosis was diagnosed by evaluating a trans-tracheal aspirate and a cryptococcal latex-particle agglutination antigen titer. Clinical remission was achieved with ketoconazole administration, an imidazole antifungal agent. Serial antigen titers were used to monitor treatment, which was continued for 12 months. Ketoconazole therapy was well tolerated by the dog.

Cytochemical localization of hydrogen peroxide generating sites in the rat thyroid gland.

Sites of H2O2 generation in lightly prefixed, intact thyroid follicles were studied by two cytochemical reactions: peroxidase-dependent DAB oxidation and cerium precipitation. In both cases reaction product accumulated on the apical surface of the follicle cell at the membrane-colloid interface. The former reaction was inhibited by the peroxidase inhibitor, aminotriazole; both reactions were blocked by the presence of catalase. NADH in the medium slightly increased the amount of cerium precipitation. The ferricyanide technique for oxidoreductase activity was also applied; reaction product again was associated with the apical surface. These results strongly imply that the follicle cells have a NADH oxidizing system generating H2O2 at the apical plasma membrane.