Effect of immunosuppressive drug therapy on blood urea nitrogen concentration in dogs with azotemia

Azotemic dogs receiving prednisone and azathioprine to enhance renal allograft survival had higher blood urea nitrogen (BUN):serum creatinine (SC) ratios, when compared with nontreated dogs with induced azotemia. The difference in ratios probably was attributable to increased BUN content secondary to the catabolic effects of the drugs used. However, dogs with naturally occurring renal failure had BUN:SC ratios that were similar to those for dogs receiving the catabolic drugs. It was concluded that even though catabolic drugs may influence BUN:SC ratios, the multiplicity of other factors affecting BUN and SC may interact to cause a wide range of BUN:SC ratios under conditions of naturally occurring primary renal failure in the dog.     

Ulcerative otitis externa responsive to immunosuppressive therapy in two dogs

Two middle-aged dogs were presented with bilateral severe ulcerative otitis externa without previous history of disease or evidence of other skin disease. Based on the exclusion of microbial infection and other primary causes, histopathological findings and response to immunomodulatory treatment, a diagnosis of presumed immune-mediated ulcerative otitis externa was made in both cases. However, the two cases differed with regard to their histopathological characteristics and the course of the disease. This report indicates that primary ulcerative disease needs to be considered in cases of ulcerative otitis externa which are unresponsive to appropriate antimicrobial therapy.     

Cutaneous neosporosis in two adult dogs on chronic immunosuppressive therapy.

Antemortem diagnosis of generalized ulcerative and pyogranulomatous dermatitis with numerous intralesional tachyzoites was made from skin biopsy specimens from 2 adult dogs on chronic immunosuppressive therapy. A 9-year-old Italian Greyhound was on long-term corticosteroid therapy for the treatment of a lupus-like systemic autoimmune disorder, and a 7-year-old Labrador Retriever had received several months of chemotherapy for lymphosarcoma. The tachyzoites were identified as Neospora caninum by immunoperoxidase immunohistochemistry. Both dogs were treated with clindamycin. Lesions in the Greyhound resolved; however, the Labrador Retriever was euthanized because of evidence of neuromuscular disease, despite improvement of the skin lesions. These 2 cases indicate that cutaneous neosporosis can occur in adult dogs on chronic immunosuppressive therapy. The disease may result from reactivation of a congenital infection and/or a recently acquired primary infection.     

Prolonged remission after immunosuppressive therapy in six dogs with pemphigus foliaceus

Limited information is available on the long-term outcome of treatment of pemphigus foliaceus in dogs. The purpose of this study is to report that a prolonged remission can occur after discontinuation of immunosuppressive regimens in some animals with this disease. Six dogs were diagnosed with pemphigus foliaceus based on suggestive clinical signs and histopathology. These patients were treated either with immunosuppressive doses of oral glucocorticoids or with a combination of oral glucocorticoids and azathioprine. After clinical signs underwent complete remission, which occurred 1.5-5 months after immunosuppression was initiated, the drugs were tapered progressively and eventually withdrawn. The total duration of immunosuppressive therapy varied between 3 and 22 months. Skin lesions of pemphigus foliaceus did not recur for 1.5-6 years after treatment was stopped. These observations suggest that, in some dogs with pemphigus foliaceus, immunosuppression can lead to long-term remission of skin lesions, and that discontinuation of treatment is not necessarily followed by a recurrence of clinical signs.     

Lesions in dogs following renal transplantation and immunosuppression

Renal allografts were transplanted into 20 dogs (12 beagles, eight mongrels) following a prescribed protocol for pre-transplantation blood transfusions and kidney exchange. Immunosuppressive therapy (azathioprine and prednisone) was modified as needed for each dog. Seven of the beagle dogs survived for 1 year and were then euthanized; all other dogs died or were euthanized prior to 1 year post-transplantation. Graft rejection and renal failure were the greatest causes of mortality. Renal lesions which contributed to the death of some animals included renal vein thrombosis, nephrosis, and pyelonephritis. Inflammation of the lower respiratory tract (bronchitis, pneumonia, and pleuritis) was a contributory cause of death in some dogs. Cystitis and ureteritis occurred in almost half of the dogs. Prostatitis was seen in six of the 16 male dogs. Adrenal cortical atrophy, parathyroid gland hyperplasia, and bone marrow hypocellularity were seen in a majority of the dogs which survived 1 year.     

Intussusception following renal transplantation in dogs (author's transl)]

In a consecutive and non-selected study of 54 kidney transplanted dogs, 12 cases of intussusception of the small intestine developed in 8 dogs. The patogenesis is still unknown. It has been postulated that the time of the operation (4--7 hours) and the segmental termination of the post-operative atony in the intestine are essential factors in this fatal complication. The last 16 dogs in this material were peroperatively treated with antikolinergics (Mestinon NFN), which was continued until normal function of the intestine. In these dogs there were no evidence of intussusception. The value of this profylaxis is open to discussion and it is essential to solve the problem of intussusception through a "blind" and controlled trial.     

Kidney transplantation in dogs with naturally occurring end-stage renal disease

Renal allografts were performed between unrelated donors and 15 dogs with naturally occurring end-stage renal disease. Donor selection was based on compatible dog erythrocyte antigen typing and cross-matching. An immunosuppressive protocol consisting of rabbit antidog antithymocyte serum, cyclosporin-A, azathioprine, and prednisone was used to control postoperative rejection of the donated kidney. Although seven animals died because of technical failures or rejection episodes, a median survival time of eight months has been achieved, with two dogs living for longer than five years after surgery. Long-term survivors have died from a variety of problems not related to renal allograft rejection.     

Acute vascular and interstitial rejection following renal allograft transplantation in dogs

Renal allograft transplantation was performed in four beagles. Immunosuppressive treatment using cyclosporine, mizoribin and prednisolone was continued from Day 5 pre- until Day 20 post-transplantation. Between Days 28 and 32 post-transplantation, an abrupt elevation of the serum creatinine values followed by the development of uremia was seen in all recipients. Histopathology of the allografts examined between Days 28 and 37 revealed edema, necrosis, hemorrhage and severe diffuse interstitial cellular infiltration as well as tubulitis. Glomerular changes notably included swelling of the tufts due to hypercellularity, which was consistent with transplant glomerulitis. The intrarenal arteries exhibited fibrinoid necrosis of the walls and intimal or transmural cellular infiltration. These renal lesions were consistent with those of acute vascular and interstitial rejection in humans.     

Use of capecitabine after renal allograft transplantation in dog erythrocyte antigen-matched dogs

OBJECTIVES: To investigate the use of a capecitabine (CAP)-based regimen after renal transplantation in dogs. STUDY DESIGN: Prospective, pilot study. ANIMALS: Healthy, unrelated, dog erythrocyte antigen (DEA)-matched, adult beagles. METHOD: Standard heterotopic renal transplantation with native nephrectomy was performed in 7 dogs. Dogs received oral, twice daily, CAP (250 mg/m2), cyclosporine-A (CsA) (4 mg/kg), ketoconazole (5 mg/kg), and prednisolone (0.25 mg/kg). After 90 days the surviving dogs were euthanatized and complete necropsy was performed. RESULTS: Seven transplants were performed. All dogs survived surgery. Six dogs had acute neurotoxicity, which resulted in death or euthanasia of 2 dogs within 2 days of surgery. In the remaining dogs, toxicity resolved rapidly with cessation of drug administration. Thereafter, modification of the regimen minimized toxicity. The 5 remaining dogs survived to study end; 4 dogs had no evidence of graft rejection. Necropsy examination was mostly unremarkable in all dogs. There were no major changes in CBC or biochemical values, except for a significant increase in serum calcium. CONCLUSIONS: CAP appeared well tolerated in most dogs. Toxicity occurred but abated with modification of the drug regimen. Efficacy for postoperative immunosuppression cannot be determined by this study, although results are promising. CLINICAL RELEVANCE: CAP-CsA-prednisolone is an effective, oral immunosuppressive regimen for prevention of acute allograft rejection in DEA-matched beagles. Further studies on dose, toxicity, and efficacy compared with current immunosuppressive regimens are needed before use in clinical practice.     

Renal allograft histopathology in dog leukocyte antigen mismatched dogs after renal transplantation

OBJECTIVE: To evaluate allograft histopathology in dog leukocyte antigen (DLA)-mismatched dogs undergoing renal transplantation, with transient immunosuppression. STUDY DESIGN: Prospective study. ANIMALS: Ten healthy adult mongrel dogs. METHODS: Reciprocal renal transplantation and bilateral nephrectomy were performed. Immune conditioning consisted of nonmyeloablative (200 cGy), total body irradiation (TBI), bone marrow transplantation (BMT; 7 dogs), cyclosporine (CSA; 15 mg/kg every 12 hours), mycophenolate mofetil (MMF; 10 mg/kg every 12 hours) and intermittent prednisone (1 mg/kg every 12-24 hours). Biopsies were collected at transplantation, during full immunosuppression (44-90 days), and once medications were reduced or discontinued (228-580 days). Biopsies were evaluated for interstitial, tubular, vascular, and glomerular lesions. Blood urea nitrogen, creatinine, serum CSA concentrations, and clinical score were determined at each biopsy. RESULTS: Seven dogs survived >200 days (mean, 380 days). Transient CSA toxicity was suspected in 6 dogs. Lymphocytic, plasmacytic interstitial inflammation, and tubulitis progressed when immunosuppressive medications were decreased. All 7 dogs had histologic lesions consistent with some degree of allograft rejection at study end. CONCLUSION: Nonmyeloablative TBI, BMT, and short-term immunosuppression with CSA, MMF, and prednisone allowed renal allograft function and dog survival for >200 days. It appears unlikely that total drug withdrawal will be possible in unrelated DLA-mismatched dogs using this protocol. CLINICAL RELEVANCE: Transient immunosuppression with MMF, CSA, and prednisone along with BMT and nonmyeloablative TBI may make kidney transplantation a clinical reality for treatment of kidney failure in dogs. Initiating both MMF and CSA at lower dosages may potentially eliminate early renal allograft injury.     

Experimental drug therapy for respiratory disorders in dogs and cats.

Experimental therapy in veterinary medicine is based on empiric reasoning. If a particular therapy is labeled experimental, it means that its effectiveness has not been demonstrated scientifically. Empiric therapy is experimental and is based on experience, not on scientific proof. The purpose of this article is to suggest the use of specific experimental drug therapies for certain respiratory disorders in dogs and cats.     

First-choice therapy for dogs presenting with diarrhoea in clinical practice

Computerised referral histories were reviewed for dogs admitted to the University of Liverpool Small Animal Teaching Hospital between January 2000 and December 2008 with diarrhoea among the clinical signs. A total of 371 cases presenting to the referring veterinary surgeon were included in the study, and information was compiled regarding signalment, clinical signs and treatment given at the initial consultation. Various breeds, ages and sexes were represented. Antibacterials were used in 263 (71 per cent) cases, steroids in 71 (19 per cent) cases and miscellaneous antidiarrhoeal products (including probiotics, prebiotics, adsorbents and antimotility drugs) in 98 (26 per cent) cases. Other drugs used included antiemetics (48 of 371 [13 per cent] cases), gastric protectants (37 of 371 [10 per cent] cases) and sulfasalazine (26 of 371 [7 per cent] cases). Antibacterial administration was positively associated with hyperthermia (odds ratio [OR]=2.97, P=0.012) and anorexia (OR=2.17, P=0.0075), but negatively associated with both weight loss (OR=0.55, P=0.036) and tenesmus (OR=0.43, P=0.035). In contrast, use of antidiarrhoeal products was positively associated with the presence of faecal mucus (OR=1.77, P=0.043), and negatively associated with vomiting (OR=0.57, P=0.025) and weight loss (OR=0.52, P=0.033).     

Adverse drug reactions in the treatment of filarial parasites: clinical reactions to diethylcarbamazine therapy in dogs infected with Dirofilaria immitis in Australia

The clinical signs associated with reactions to diethylcarbamazine therapy in dogs infected with Dirofilaria immitis include depression, vomiting and diarrhoea followed by bradycardia, softened heart sounds, weakened apex beat, low amplitude arterial pulse, pale mucosa, poor mucosal capillary refill and polypnoea. Subsequently the dogs become laterally recumbent and exhibit tachycardia and dyspnoea, with associated hepatomegaly and abdominal wall contractures. These signs are described in a group of eight reactive dogs and the possible pathophysiology, which is consistent with cardiac depression and hypovolaemic shock, is discussed.