Evaluation of the Clinical and Histologic Features of Renal Allograft Rejection in Cats

OBJECTIVES: To describe the clinical signs and histopathologic features of renal allograft rejection in cats, and to provide a historical, untreated control group for use in future studies of feline renal allograft rejection. ANIMALS: Fourteen adult research cats. METHODS: Renal transplantation and bilateral nephrectomy were performed in pairs of immunogenically mismatched cats. A physical examination was performed, and packed cell volume, total protein, and plasma creatinine concentrations were measured each day after surgery. The cats were euthanatized when plasma creatinine concentration exceeded 7 mg/dL or when weight loss exceeded 20%. Renal histopathology was scored according to the Banff 97 criteria by 3 pathologists. RESULTS: Nine cats completed the study. Plasma creatinine exceeded 7 mg/dL in 5 cats, weight loss exceeded 20% in 3 cats, and 1 cat was found dead. Clinical signs in cats with rejection were nonspecific or absent. Rectal temperature decreased by 0.8 +/- 0.5 degrees C in the 24 hours before euthanasia. The pathologists agreed on the allograft histopathologic category in 6 of 9 cats. The histologic consensus was acute/active rejection in 8 cats and normal in 1 cat. Median survival time of the 8 cats with histologically confirmed allograft rejection was 23 days (range, 8-34 days). CONCLUSIONS AND CLINICAL RELEVANCE: Renal allograft rejection is associated with minimal clinical signs. Therefore, plasma creatinine concentration should be measured routinely in patients with a functioning allograft. An increase in plasma creatinine concentration is highly suspicious for allograft rejection, although a biopsy of the renal allograft is needed for definitive diagnosis.     

The effect of rectal temperature on perianesthetic serum concentrations of transdermally administered fentanyl in cats anesthetized with isoflurane

OBJECTIVES: To determine whether moderate hypothermia during 4 hours of anesthesia with isoflurane substantially affects serum concentrations of transdermally administered fentanyl in the perianesthetic period in cats. ANIMALS: 7 healthy mature cats. PROCEDURE: A fentanyl patch (25 microg/h) was applied to the shaved thorax 24 hours before induction of anesthesia. Anesthesia was induced at time 0. Each cat received 2 treatments in a random order. Treatments were isoflurane anesthesia with normothermia and isoflurane anesthesia with hypothermia. Cats were intubated, connected to a nonrebreathing circuit, and maintained at 1.3X minimum alveolar concentration for 4 hours. Cats in the hypothermia treatment groups were actively cooled to 35 degrees C following the induction of anesthesia. Serum fentanyl analysis was performed at -24, -12, 0, 1, 2, 3, 4, 4.5, 5, 6, 7, 8, 9, 10, 12, and 24 hours. RESULTS: Mean +/- SEM serum fentanyl concentration (SFC) for the hypothermia treatment group (0.598 +/- 0.3048 ng/mL) was significantly lower than the baseline concentration (1.834 +/- 0.6393 ng/mL) at 1 hour. This significant reduction persisted for the duration of anesthesia for the hypothermia treatment group. Serum fentanyl concentrations returned to baseline values within 1 hour of the end of anesthesia, regardless of body temperature. CONCLUSIONS AND CLINICAL RELEVANCE: Hypothermia during inhalant anesthesia induced a significant reduction in SFC obtained with transdermal administration. The impact of this reduction in SFC on the contribution of transdermally administered fentanyl to any reduction in the need for inhalant anesthesia remains to be determined.     

Possible Hemolytic Uremic Syndrome in Three Cats After Renal Transplantation and Cyclosporine Therapy

OBJECTIVE: To describe the clinical history of 3 cats with possible hemolytic uremic syndrome (HUS) after renal transplantation. STUDY DESIGN: This case series documents historical findings, physical examination findings, clinical pathologic features, necropsy and histopathologic findings of 3 cats with possible HUS. RESULTS: Two cats had chronic renal failure; 1 cat had acute renal failure secondary to ethylene glycol toxicity. A renal transplant was performed in each of the 3 cats without obvious problems. Complications that would support a diagnosis of HUS, including anemia, thrombocytopenia, and azotemia occurred within 24 hours in 1 cat, within 8 days in a second cat, and 2 months after transplantation in the third cat. In 2 cats, HUS was likely secondary to cyclosporine immunosuppression. In the third cat, HUS may have been secondary to allograft rejection. Renal biopsies from all 3 cats were suggestive of HUS. CONCLUSION AND CLINICAL RELEVANCE: In human beings, HUS in transplant recipients may occur secondary to immunosuppressive drugs, vascular rejection, or recurrence of original disease. Graft loss occurred in all 3 cats in this study and the mortality rate was 100%. Clinicians caring for these patients need to be aware of this disorder because early recognition and treatment is critical in the management of post-transplant HUS.     

Comparison of 3 techniques for ureteroneocystostomy in cats

OBJECTIVE: To compare 3 techniques for ureteroneocystostomy in cats. STUDY DESIGN: Experimental surgical study. ANIMALS: Fifteen adult cats. METHODS: Cats (15) had ureteroneocystostomy with ureteronephrectomy of the contralateral kidney: 5 cats had an intravesical mucosal apposition technique (modified Leadbetter-Politano; intravesical-MA group), 5 cats had extravesical ureteroneocystostomy (modified Lich Gregoir) using a simple continuous suture pattern (extravesical-SC group) and 5 cats had an extravesical technique using a simple interrupted suture pattern (extravesical-SI group). Renal function was evaluated by measuring serum creatinine concentration. Ultrasonographic assessment of the kidney and ureteroneocystostomy site was performed the day after surgery, twice weekly for 3 weeks and once weekly for the remainder of the study. Cats were euthanatized 50 days after surgery. The kidney and ureter removed at surgery, the remaining kidney, ureter, ureteroneocystostomy site, and bladder were examined histologically. RESULTS: Two extravesical-SC cats were euthanatized because of azotemia and uroabdomen, and 1 died acutely at day 4 for unknown reasons. In the intravesical-MA and extravesical-SI cats, the serum creatinine concentration increased after surgery, peaking at a mean (+/-SD) of 9.4+/-2.4 mg/dL and 4.9+/-3.3 mg/dL on day 3, and decreasing to 3.4+/-5.7 mg/dL and 1.5+/-0.4 mg/dL on day 7, respectively. The extravesical-SI technique was associated with consistently lower serum creatinine concentrations for the first week after surgery compared with the other techniques. The mean serum creatinine concentration was within the reference range in cats in the intravesical-MA and extravesical-SI groups by days 10 and 5, respectively. Renal pelvic dilatation occurred in all cats but resolved more rapidly in cats after extravesical techniques. There was no significant difference in serum creatinine concentrations or renal pelvic dilation between the intravesical-MA and extravesical-SI techniques. Bladder mass height at the anastomosis site was significantly larger and persisted for longer with intravesical-MA technique. CONCLUSION: An extravesical-SI technique is seemingly the choice for ureteroneocystostomy in cats with undilated ureters. Renal pelvic dilation on ultrasound examination should be expected after ureteroneocystostomy in cats. CLINICAL RELEVANCE: An extravesical ureteroneocystostomy technique using a simple interrupted pattern for anastomosis should be considered in cats undergoing renal transplantation.     

Microemulsified cyclosporine-based immunosuppression for the prevention of acute renal allograft rejection in unrelated dogs: preliminary experimental study

OBJECTIVES: To determine whether the microemulsified formulation of cyclosporine (MCsA; Neoral; Novartis A.G.), combined with azathioprine (Imuran; Glaxo Wellcome), and prednisolone (Delta-Cortef; Upjohn), would be effective in preventing acute renal allograft rejection in unrelated mongrel dogs. To document any toxic effects associated with this drug combination. STUDY DESIGN: rospective, pilot study. ANIMALS: Four healthy, adult, mongrel, canine renal allograft recipients. METHODS: Heterotopic renal transplantation, with bilateral nephrectomy, was performed in 4 dogs. Allografts were harvested from 2 unrelated dogs that were to be euthanatized for reasons unrelated to this study. The dogs were treated for 100 days or until signs of illness or allograft rejection required euthanasia. Microemulsified cyclosporine (20 mg/kg/day), azathioprine (5 mg/kg every other day), and prednisolone (1 mg/kg/day) were administered for the prevention of acute rejection. Body weight, serum biochemistry profiles, complete blood counts, and trough whole-blood cyclosporine concentrations were measured throughout the study. Cyclosporine dose was adjusted to maintain a trough concentration of 400-500 ng/mL. Azathioprine dose was decreased if evidence of hepatotoxicity developed or if the total blood white cell count was <4,000 cells/micro L. The prednisolone was tapered by 0.25 mg/kg increments every 3 weeks and discontinued 14 days before the end of the study in the surviving dogs. Complications were recorded. A complete necropsy and histopathologic examination were performed in each recipient. RESULTS: Two of the 4 dogs survived the 100-day period. One dog was euthanatized at 8 days because of an intestinal intussusception. One dog was euthanatized at 64 days because of a severe upper respiratory infection. At the time of death, these 2 dogs had plasma creatinine concentrations of 1.5 and 2.6 mg/dL, respectively, with no histopathologic evidence of allograft rejection. All dogs had transient weight loss (range, 4.6%-17.7% of preoperative body weight) between days 7 and 14. Two dogs had evidence of hepatotoxicity. The 2 dogs surviving to 100 days had normal serum creatinine concentrations and no clinical signs of rejection. One of these dogs had evidence of a grade IIa acute/active rejection based on the modified BANFF 97 histopathologic classification. The second dog had no evidence of rejection or inflammation within the allograft. CONCLUSIONS: This preliminary experimental study shows that immunosuppression using MCsA, combined with azathioprine and prednisolone, may be effective in preventing acute renal allograft rejection in unrelated mongrel dogs for 100 days. Complications included ileocolic intussusception, upper respiratory infection, weight loss, and transient hepatotoxicity. CLINICAL RELEVANCE: Immunosuppression using MCsA, azathioprine, and prednisolone may be effective in preventing acute renal allograft rejection in unrelated, mongrel dogs. This triple drug protocol is cost-effective and was easy to administer. Further investigation is warranted to minimize toxic effects and to determine the efficacy of prophylactic renal biopsies to detect and treat subclinical acute/active rejection.     

Evaluation of the prevalence of infections in cats after renal transplantation: 169 cases (1987-2003)

OBJECTIVE: To determine the prevalence of infections developing postoperatively, document the contribution of infection to increased risk of death, and identify risk factors associated with the development of infectious complications in cats after renal transplantation. DESIGN: Retrospective study. ANIMALS: 169 cats that received renal allograft transplants. PROCEDURES: Medical records of cats receiving renal transplants at the University of California from January 1987 through December 2003 were reviewed. RESULTS: 47 infections developed in 43 of 169 cats. Bacterial infections were most common (25/47 cats), followed by viral (13/47), fungal (6/47), and protozoal (3/47) infections. The median duration from transplant surgery to development of infection was 2.5 months. Infection was the second most common cause of death after acute rejection of the transplant, accounting for 14% of deaths overall. Cats with concurrent diabetes mellitus had a significantly increased risk of developing an infection after renal transplantation. Sex, increasing age, concurrent neoplasia, and previous treatment for transplant rejection were not associated with development of infection. CONCLUSIONS AND CLINICAL RELEVANCE: Infection was a common complication and an important cause of death or euthanasia in cats after renal transplantation. Development of diabetes mellitus after transplantation significantly increased the risk of infection.     

Evaluation of the effects of ischemic injury and ureteral obstruction on delayed graft function in cats after renal autotransplantation

OBJECTIVE: To determine the relative importance of ischemic injury to delayed graft function (DGF) in cats. STUDY DESIGN: Experimental study. ANIMALS: Six intact female cats. METHODS: Cats had renal autograft transplantation without ureteral transection and reimplantation and a contralateral nephrectomy. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured regularly and abdominal ultrasound was performed before surgery, the day after surgery and twice weekly thereafter. Ultrasound-guided renal biopsy was performed on day 7. Cats were euthanatized on day 21. Histology of the autograft, ureter, bladder, vascular anastomoses sites, and contralateral kidney were performed. Observations were compared with those from an historic group of research cats that had extravesicular ureteroneocystostomy and contralateral nephrectomy. RESULTS: Five cats completed the study. Serum creatinine and BUN concentrations increased after surgery, peaking at 3.2+/-0.8 and 77.6+/-15.9 mg/dL, respectively, 1-2 days after surgery. Serum creatinine concentration returned to the reference interval by 6 days after surgery. BUN gradually decreased in all cats but did not return to the reference interval by study end. Serum creatinine and BUN concentrations were consistently lower but not significantly so (P=.29 and .56, respectively) compared with the historic ureteroneocystostomy group. No ultrasonographic abnormalities or renal biopsy histologic abnormalities were observed. At necropsy, 1 autograft had generalized interstitial fibrosis. CONCLUSION: Harvesting the renal graft and the ischemia before revascularization causes impaired renal function after engraftment. CLINICAL RELEVANCE: The process of harvesting and reimplanting the renal graft can contribute to DGF in cats, independent of ureteral obstruction.     

Plasma fentanyl concentrations and analgesic effects during full or partial exposure to transdermal fentanyl patches in cats

OBJECTIVE: To compare plasma fentanyl concentrations and analgesic efficacy during full or partial exposure to 25-microg/h transdermal fentanyl patches (TFPs) in cats undergoing ovariohysterectomy. DESIGN: Randomized controlled clinical trial. ANIMALS: 16 client-owned cats. PROCEDURE: Cats were randomly assigned to receive full or partial exposure to a TFP; patches were applied approximately 24 hours prior to ovariohysterectomy. Rectal temperature, heart rate, respiratory rate, blood glucose concentration, and blood pressure were measured and pain severity was assessed periodically for 72 hours after patch application. Venous blood samples were collected for determination of plasma fentanyl concentration 0, 6, 12, 18, 24, 36, 48, 60, and 72 hours after patch application. RESULTS: Mean +/- SD steady state plasma fentanyl concentration in cats in the full TFP exposure group (1.78 +/- 0.92 ng/mL) was significantly greater than concentration in cats in the partial exposure group (1.14 +/- 0.86 ng/mL). Steady state plasma fentanyl concentrations were evident between 18 and 72 hours after patch application. Subjective scores used to evaluate analgesic efficacy were not significantly different between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that delivery of fentanyl from TFPs can be reduced by decreasing the amount of exposed surface area. In cats weighing < 4 kg (9 lb), exposure to half a 25-microg/h TFP appears to provide adequate analgesia following ovariohysterectomy.     

Anticoagulant effects of low-molecular-weight heparins in healthy cats

BACKGROUND: Low-molecular-weight heparin (LMWH) has potential benefit in cats at risk for thromboembolic disease. However, LMWH pharmacokinetics has not been characterized in the cat. Drug effect with LMWH may be evaluated with analysis of factor Xa inhibition (anti-Xa) or thromboelastography (TEG). HYPOTHESIS: Administration of LMWH at previously recommended dosages and schedules to healthy cats will result in inhibition of factor Xa and hypocoagulable TEG. ANIMALS: In vivo research with heparin was performed in 5 purpose-bred cats. METHODS: In a prospective study with randomized crossover design, heparin or placebo was administered. Treatments were unfractionated heparin (UFH), 250 IU/kg q6h; dalteparin, 100 IU/kg q12h; enoxaparin, 1 mg/kg q12h; or 0.9% saline, 0.25 mL/kg q6h. Each drug was administered for 5 consecutive days followed by a minimum washout of 14 days. Baseline and post-treatment analyses included anti-Xa, TEG, and prothrombin time/activated partial thromboplastin time. RESULTS: Mean anti-Xa activity 4 hours after enoxaparin (0.48 U/mL) approached the human therapeutic target (0.5-1.0 U/mL); however, mean trough anti-Xa activity was below detection limits. Mean anti-Xa activity 4 hours after dalteparin was lower, and only 1 cat attained therapeutic target at a single time point. Cats receiving UFH attained target anti-Xa activity and changes in TEG at trough and 4 hours. CONCLUSIONS: Cats have rapid absorption and elimination kinetics with LMWH therapy. On the basis of pharmacokinetic modeling, cats will require higher dosages and more frequent administration of LMWH to achieve human therapeutic anti-factor Xa activity of 0.5-1 U/mL. Peak anti-Xa activity is predicted at 2 hours after administration of LMWH.     

Pharmacokinetics and safety of penciclovir following oral administration of famciclovir to cats

OBJECTIVE: To investigate penciclovir pharmacokinetics following single and multiple oral administrations of famciclovir to cats. ANIMALS: 8 adult cats. PROCEDURES: A balanced crossover design was used. Phase I consisted of a single administration (62.5 mg, PO) of famciclovir. Phase II consisted of multiple doses of famciclovir (62.5 mg, PO) given every 8 or 12 hours for 3 days. Plasma penciclovir concentrations were assayed via liquid chromatography-mass spectrometry at fixed time points after famciclovir administration. RESULTS: Following a single dose of famciclovir, the dose-normalized (15 mg/kg) maximum concentration (C(max)) of penciclovir (350 +/- 180 ng/mL) occurred at 4.6 +/- 1.8 hours and mean +/- SD apparent elimination half-life was 3.1 +/- 0.9 hours. However, the dose-normalized area under the plasma penciclovir concentration-time curve extrapolated to infinity (AUC(0-->)) during phase I decreased with increasing dose, suggesting either nonlinear pharmacokinetics or interindividual variability among cats. Accumulation occurred following multiple doses of famciclovir administered every 8 hours as indicated by a significantly increased dose-normalized AUC, compared with AUC(0-->) from phase 1. Dose-normalized penciclovir C(max)following administration of famciclovir every 12 or 8 hours (290 +/- 150 ng/mL or 780 +/- 250 ng/mL, respectively) was notably less than the in vitro concentration (3,500 ng/mL) required for activity against feline herpesvirus-1. CONCLUSIONS AND CLINICAL RELEVANCE: Penciclovir pharmacokinetics following oral famciclovir administration in cats appeared complex within the dosage range studied. Famciclovir dosages of 15 mg/kg administered every 8 hours to cats are unlikely to result in plasma penciclovir concentrations with activity against feline herpesvirus-1.     

Comparison of pharmacodynamic variables following oral versus transdermal administration of atenolol to healthy cats

OBJECTIVE: To describe the disposition of and pharmacodynamic response to atenolol when administered as a novel transdermal gel formulation to healthy cats. ANIMALS: 7 healthy neutered male client-owned cats. PROCEDURES: Atenolol was administered either orally as a quarter of a 25-mg tablet or as an equal dose by transdermal gel. Following 1 week of treatment, an ECG and blood pressure measurements were performed and blood samples were collected for determination of plasma atenolol concentration at 2 and 12 hours after administration. RESULTS: 2 hours after oral administration, 6 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 579 +/- 212 ng/mL. Two hours following transdermal administration, only 2 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 177 +/- 123 ng/mL. The difference in concentration between treatments was significant. Trough plasma atenolol concentrations of 258 +/- 142 ng/mL and 62.4 +/- 17 ng/mL were achieved 12 hours after oral and transdermal administration, respectively. A negative correlation was found between heart rate and plasma atenolol concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol.     

Renal transplantation for treatment of end-stage renal failure in cats.

Renal transplantation was performed as treatment of end-stage renal failure in 23 cats. Twenty-two cats had chronic renal disease and 1 cat had acute renal disease associated with ethylene glycol-induced toxicosis. Sixteen cats were discharged from the hospital. Nine survived a mean of 8.4 +/- 6.5 months, and 7 cats continue to survive at the time of this report (mean 12.6 months). Seven cats died within 2 weeks of surgery. All renal allografts were obtained from unrelated blood-crossmatch-compatible donors. No deaths were attributable to acute renal allograft rejection, demonstrating the successful maintenance of renal allografts by use of cyclosporine and prednisolone immunosuppression in cats.     

Comparison of pharmacokinetics of fentanyl after intravenous and transdermal administration in cats

OBJECTIVE: To compare pharmacokinetic and pharmacodynamic characteristics of fentanyl citrate after IV or transdermal administration in cats. ANIMALS: 6 healthy adult cats with a mean weight of 3.78 kg. PROCEDURE: Each cat was given fentanyl IV (25 mg/cat; mean +/- SD dosage, 7.19 +/- 1.17 mg/kg of body weight) and via a transdermal patch (25 microg of fentanyl/h). Plasma concentrations of fentanyl were measured by use of radioimmunoassay. Pharmacokinetic analyses of plasma drug concentrations were conducted, using an automated curve-stripping process followed by nonlinear, least-squares regression. Transdermal delivery of drug was calculated by use of IV pharmacokinetic data. RESULTS: Plasma concentrations of fentanyl given IV decreased rapidly (mean elimination half-life, 2.35 +/- 0.57 hours). Mean +/- SEM calculated rate of transdermal delivery of fentanyl was 8.48 +/- 1.7 mg/h (< 36% of the theoretical 25 mg/h). Median steady-state concentration of fentanyl 12 to 100 hours after application of the transdermal patch was 1.58 ng/ml. Plasma concentrations of fentanyl < 1.0 ng/ml were detected in 4 of 6 cats 12 hours after patch application, 5 of 6 cats 18 and 24 hours after application, and 6 of 6 cats 36 hours after application. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, transdermal administration provides sustained plasma concentrations of fentanyl citrate throughout a 5-day period. Variation of plasma drug concentrations with transdermal absorption for each cat was pronounced. Transdermal administration of fentanyl has potential for use in cats for long-term control of pain after surgery or chronic pain associated with cancer.     

Effects of the calcium channel antagonist amlodipine in cats with surgically induced hypertensive renal insufficiency

OBJECTIVE: To determine whether amlodipine besylate decreases systemic arterial blood pressure (BP) and reduces the prevalence of complications in cats with induced hypertensive renal insufficiency. ANIMALS: 20 cats with partial nephrectomy. PROCEDURE: Following reduction in renal mass, 10 cats were administered 0.25 mg of amlodipine/kg, PO, q 24 h (group A). Ten cats served as a control group (group C). Systolic BP (SBP), diastolic BP (DBP), and mean BP (MBP), physical activity, and pulse rate were measured continuously for 36 days by use of radiotelemetric devices. RESULTS: Compared with values for clinically normal cats, SBP, DBP, and MBP were significantly increased in cats of group C. Cats in group A had significant reductions in SBP, DBP, and MBP, compared with values for cats in group C. Albuminuria but not urine protein-to-creatinine ratio was significantly correlated (R2 = 0.317) with SBP in hypertensive cats. Prevalence of ocular lesions attributable to systemic hypertension in group C (7 cats) was greater than that observed in group A (2). Two cats in group C were euthanatized on day 16 because of nuerologic complications attributed to systemic hypertension. One normotensive cat in group A was euthanatized because of purulent enteritis of unknown cause on day 27. CONCLUSIONS AND CLINICAL RELEVANCE: Amlodipine had an antihypertensive effect in cats with coexistent systemic hypertension and renal insufficiency. Its use may improve the prognosis for cats with systemic hypertension by decreasing the risk of ocular injury or neurologic complications induced by high BP.     

Neosporosis in cats

Six cats (Nos. 1-6) were inoculated intramuscularly with (1 x 10(6)) and orally (5 x 10(5)) tachyzoites of Neospora caninum. Three (Nos. 1-3) of the six cats were given 40 mg/kg methylprednisolone acetate 7 days before and on the day of inoculation with N. caninum tachyzoites, and three cats (Nos. 4-6) were not given methylprednisolone acetate. Two of the cats (cat Nos. 1 and 2) given methylprednisolone acetate died suddenly. Cat No. 1 died 8 days post-inoculation, and cat No. 2 died 16 days post-inoculation. Cat No. 3 was euthanatized 21 days post-inoculation. Cat No. 1 had lesions of gram-positive bacterial septicemia. Necrotizing encephalitis, myelitis, disseminated skeletal muscle necrosis, hepatic necrosis, interstitial pneumonia, and renal tubular necrosis were the main lesions in cat Nos. 2 and 3. The cats that were not given methylprednisolone acetate remained clinically normal except for slight weight loss in cat No. 6. All three of these cats were euthanatized 55 days post-inoculation. Mild myositis and encephalitis were noted on microscopic examination of tissues from these three cats. Neuromuscular lesions were not seen in six control cats (Nos. 7-12) not inoculated with N. caninum and euthanatized 21 or 22 days after administration of the first two doses of methylprednisolone acetate (40 mg/kg), given at a weekly interval.     

Evaluation of the clinical efficacy of benazepril in the treatment of chronic renal insufficiency in cats

BACKGROUND: Chronic renal insufficiency (CRI) is a common disease in cats. Angiotensin-converting enzyme inhibitors (ACEI) have beneficial effects in humans with CRI by reducing the loss of protein in the urine and increasing life expectancy. HYPOTHESIS: The ACEI benazepril has beneficial effects on survival, clinical variables, or both as compared with placebo in cats with CRI. ANIMALS: 61 cats with naturally occurring CRI. METHODS: The cats were enrolled into a prospective, randomized, double-blind, placebo-controlled clinical trial. Cats received placebo or 0.5-1 mg/kg benazepril once daily for up to 6 months. RESULTS: Urine protein/urine creatinine ratios were significantly (P < .05) lower with benazepril as compared with placebo at days 120 and 180. Three cats with placebo and 1 cat with benazepril were removed prematurely from the study because of deterioration of CRI or death. Cats were classified into 4 stages of CRI according to the International Renal Interest Society (IRIS) classification scheme. Incidence rates of cats with IRIS classification stage 2 or stage 3 that remained in stage 2 or 3 without progressing to stage 4 were higher with benazepril (93 +/- 5%) as compared with placebo (73 +/- 13%). CLINICAL IMPORTANCE: These results suggest a potential for benazepril to delay the progression of disease, extend survival time, or both in cats with CRI.     

Evaluation of transdermal fentanyl patches for analgesia in cats undergoing onychectomy

OBJECTIVE: To evaluate efficacy and safety of using transdermal fentanyl patches (TFP) for analgesia in cats undergoing onychectomy. DESIGN: Randomized controlled clinical trial. ANIMALS: 45 client-owned cats weighing > or = 2.7 kg (5.9 lb) undergoing onychectomy, onychectomy and ovariohysterectomy, or onychectomy and castration. PROCEDURE: Cats were randomly assigned to be treated with a TFP (25 micrograms/h) or butorphanol; TFP were applied a minimum of 4 hours before surgery (approx 8 hours prior to extubation). Rectal temperature, heart rate, respiratory rate, force applied by the forelimbs, and serum fentanyl concentration were measured, and temperament, recovery, degree of sedation, severity of pain, severity of lameness, and appetite were scored before and periodically for up to 40 hours after surgery. RESULTS: Cats treated with a TFP had better recovery scores at 2 of 4 evaluation times, lower sedation scores at 2 of 8 evaluation times, and lower pain scores at 6 of 8 evaluation times, compared with cats treated with butorphanol. Use of a pressure-sensitive mat to evaluate force applied by the forelimbs did not reveal any differences between groups but did reveal a significant difference between preoperative and postoperative values. Mean +/- SD serum fentanyl concentrations were 1.56 +/- 1.08, 4.85 +/- 2.38, 4.87 +/- 1.56, and 4.35 +/- 2.97 ng/ml approximately 8, 24, 32, and 48 hours, respectively, after TFP placement. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of a TFP (25 micrograms/h) for postoperative analgesia in cats undergoing onychectomy with or without surgical sterilization is safe and effective.     

An evaluation of combined immunosuppression with MNA 715 and microemulsified cyclosporine on renal allograft rejection in mismatched mongrel dogs

OBJECTIVE: To evaluate a combination of MNA 715 and microemulsifed cyclosporine for the prevention of renal allograft rejection in mismatched mongrel dogs. STUDY DESIGN: Randomized, experimental study. ANIMALS: Fourteen female mismatched mongrel dogs. METHODS: Heterotopic renal transplantation and bilateral nephrectomy were performed in each dog. Dogs were randomly assigned to receive either MNA 715 and cyclosporine (n = 8) or cyclosporine alone (n = 6). Dogs were killed at 100 days after transplantation or when plasma creatinine exceeded 7 mg/dL. RESULTS: In the cyclosporine and MNA 715 group: 4 dogs survived to 100 days with normal plasma creatinine concentrations; 2 dogs with intestinal intussusceptions were killed at 5 and 8 days, 1 dog with a wound infection and sepsis was killed at 14 days, and 1 dog with a serum creatinine concentration >7 mg/dL was killed at 51 days postoperatively. In the cyclosporine-alone group: 3 dogs with acute rejection were killed at 6 to 9 days and 3 dogs survived to 100 days. In dogs treated with cyclosporine and MNA 715, survival to histologically confirmed acute rejection was significantly longer (P =.044) and the degree of mononuclear cell infiltration was significantly reduced (P =.040), compared with dogs treated with cyclosporine alone. CONCLUSIONS: MNA 715 combined with cyclosporine prolonged allograft survival and reduced the severity of histologic rejection in a clinically relevant renal transplant model. CLINICAL RELEVANCE: An immunosuppressive regimen consisting of MNA715 and microemulsified cyclosporine may be effective in preventing allograft rejection in canine renal transplant patients.     

Evaluation of the safety of fenbendazole in cats

OBJECTIVE: To evaluate the safety of fenbendazole in domestic cats. ANIMALS: 28 six- to seven-month old domestic short-hair cats. PROCEDURE: Cats were randomly assigned to 1 of 3 treatment groups or a control group (n = 7/group). Cats in the treatment groups were given fenbendazole at a dosage of 50, 150, or 250 mg/kg, PO, every 24 hours for 9 days; control cats were given a placebo. A fecal examination, coagulation tests, serum biochemical analyses, CBC, and urinalyses were performed before and 5, 9, and 21 days after initiation of treatment; cats were closely monitored for adverse reactions. After the last dose of fenbendazole was given, 4 control cats and 4 cats given fenbendazole at the highest dosage were euthanatized, and necropsies were performed. RESULTS: None of the cats developed any adverse reactions. For cats in the control and all treated groups, laboratory test results were within reference limits, and there were no significant differences in results of laboratory tests among groups. No gross or histologic lesions were identified in the control or treated cats that were euthanatized. CONCLUSIONS AND CLINICAL RELEVANCE: Fenbendazole administered to healthy cats at a dosage 5 times the dosage and 3 times the duration approved for use in dogs and wild felids did not cause any acute or subacute adverse reactions or pathologic changes. Results suggest that cats may be safely treated with fenbendazole.     

The effects of ketoconazole on the pharmacokinetics of cyclosporine A in cats

OBJECTIVE: To determine the effects of ketoconazole (KC) on the pharmacokinetics of cyclosporine A (CsA) elimination in cats. STUDY DESIGN: Research study and prospective clinical trial. ANIMALS: Five healthy adult cats (pharmacokinetic studies) and 6 client-owned cats with chronic renal failure. METHODS: Blood CsA concentrations were measured after CsA (4 mg/kg i.v.) administration with or without concurrent oral KC (10 mg/kg). Subsequently, a combined CsA-KC immunosuppressive regimen was used in cats after kidney transplantation. Blood CsA concentrations were measured using high performance liquid chromatography. CsA elimination was analyzed using a computerized pharmacokinetics program. RESULTS: KC increased blood CsA concentrations 1.8-fold and 2.2-fold at 12 and 24 hours after CsA administration. KC significantly decreased the mean systemic CsA clearance from 2.73 mL/min/kg to 1.22 mL/min/kg resulting in an increase in the terminal phase half-life from 10.7 to 22.2 hours. The volume of distribution of steady-state of CsA was unaffected by KC. In a series of clinical feline kidney transplant patients, a once-a-day CsA-KC regimen was able to be used in most of the cats and was effective for prevention of allograft rejection in all of these cats. CONCLUSION AND CLINICAL RELEVANCE: KC is an effective adjunct treatment for immunosuppression in feline kidney transplant patients. KC suppresses CsA elimination, which reduces the need for CsA and allows once daily administration of CsA.