An Evaluation of Combined Immunosuppression with MNA 715 and Microemulsified Cyclosporine on Renal Allograft Rejection in Mismatched Mongrel Dogs

Kyles, Andrew E.; Gregory, Clare R.; Griffey, Stephen M.; Jackson, Jordan E.; Bernsteen, Lynda; Morris, Randall E.

doi:10.1053/jvet.2002.33615

Cited by 17 publications

(29 citation statements)

References 42 publications

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“…Enteroplication prevented postoperative intestinal intussusception that was observed in previous canine renalallograft studies using MNA (13)(14)(15). Vomiting and diarrhea were the most common adverse effects.…”

Section: Adverse Effectsmentioning

confidence: 55%

“…Higher trough concentrations were associated with gastrointestinal signs such as vomiting and diarrhea. In a previous study, three of six dogs treated with Neoral survived to 100 days posttransplantation using a dose rate of 10 mg/kg twice daily and a target trough drug concentration of 500 ng/mL (15). In this study, the dose rate was reduced to 5 mg/kg twice daily, and target drug concentration was 250 ng/mL, resulting in a median survival time of 14.5 days.…”

Section: Adverse Effectsmentioning

confidence: 83%

“…In one dog, myocardial necrosis appeared to be related to an episode of acute sepsis immediately preceding acute rejection. This dog had the most severe histologic changes of acute rejection observed in the study (Banff type III), and we have previously noted more severe rejection in dogs in which sepsis preceded acute rejection (15). It is not possible to determine whether the myocardial necrosis observed in the second dog was caused by drug-mediated effects or a previous episode of sepsis or predated transplantation.…”

Section: Adverse Effectsmentioning

confidence: 88%

“…We have previously shown that a combination of FK778 (MNA715) and the microemulsified formulation of cyclosporine (Neoral, Novartis) reduced the histologic changes associated with acute allograft rejection in dogs (15). However, the dose of Neoral was chosen based on previous studies with Sandimmune, and, because the survival times observed in dogs treated with Neoral alone were better than those reported with Sandimmune, we were unable to demonstrate a statistically significant increase in survival in dogs treated with the combination of FK778 and Neoral.…”

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confidence: 99%

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Immunosuppression with a combination of the leflunomide analog, FK778, and microemulsified cyclosporine for renal transplantation in mongrel dogs

et al. 2003

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Section: Adverse Effectsmentioning

confidence: 55%

Section: Adverse Effectsmentioning

confidence: 83%

Section: Adverse Effectsmentioning

confidence: 88%

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confidence: 99%

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Immunosuppression with a combination of the leflunomide analog, FK778, and microemulsified cyclosporine for renal transplantation in mongrel dogs

et al. 2003

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“…24,25 In canine renal transplant recipients, trough whole blood cyclosporine concentrations have been recommended to be maintained between 250 and 500 ng/mL. 24,26 However, at this time, there is no evidence-based recommendation for therapeutic concentrations of cyclosporine in veterinary medicine nor is it known whether trough or peak concentrations provide the best measure of the extent of immunosuppression. Similarly, the timing and target concentrations of cyclosporine are not standardized in human medicine.…”

Section: -12mentioning

confidence: 99%

Ralstonia pickettiiSepticemia in a Dog with Immune‐Mediated Thrombocytopenia

Herrera

Burkitt

Epstein

et al. 2009

Veterinary Internal Medicne

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A 4-year-old, female spayed, Rottweiler weighing 53.3 kg presented to the William R. Pritchard Veterinary Medical Teaching Hospital (VMTH) at the University of California, Davis for the primary complaint of epistaxis of 3 days' duration. Initial physical examination revealed severe bilateral epistaxis as well as petechiation and ecchymoses along the ventrum, inner pinnae, conjunctiva, and buccal mucosa. Melena was noted on rectal examination. A CBC revealed severe thrombocytopenia (14,000/mL; reference range, 150,000-400,000/mL); mild normocytic, normochromic nonregenerative anemia (PCV, 36%; reference range, 40-55%); and a normal leukogram (9,600 WBC/mL; reference range, 6,000-13,000 WBC/mL). Serum biochemistry results included mildly increased BUN concentration (23 mg/dL; reference range, 5-21 mg/dL), increased activities of alkaline phosphatase (ALP) (835 IU/L; reference range, 21-170 IU/L) and GGT (7 IU/L; reference range, 0-6 IU/L), and mild hypercholesterolemia (406 mg/dL; reference range, 135-361 mg/dL). Urinalysis (obtained by voiding) revealed a specific gravity of 1.030 with proteinuria (30 mg/dL). A bone marrow aspirate revealed mild megakaryocytic hyperplasia consistent with immune-mediated thrombocytopenia (IMTP). Thoracic radiographs and an abdominal ultrasound were normal. Serologic titers for Ehrlichia canis, Anaplasma phagocytophilum, Rickettsia rickettsii, and Babesia canis were negative.Treatment with prednisone (1 mg/kg PO q12h) and azathioprine (1.4 mg/kg PO q24h) was initiated. The platelet count remained below 14,000/mL for 8 consecutive days and epistaxis, petechiation, and melena persisted. Because of progressive anemia (PCV, 20%) as well as clinical signs of weakness and tachycardia, a cross-matched packed red blood cell (pRBC) transfusion was administered. The dog received 300 mL of pRBCs at an initial rate of 2 mL/kg/h, which then was increased to 4 mL/kg/h. The posttransfusion PCV was 28%. Two hours after the transfusion, the dog's rectal temperature increased from 101 to 1041F. A transfusion reaction was suspected and the dog was treated with dexamethasone (0.15 mg/kg IV, once) and diphenhydramine (2.0 mg/kg SC, once). Rectal temperature decreased to 101.51F over the next 4 hours and no other adverse effects were noted. Cyclosporine (3.8 mg/kg PO q12h) was added to the treatment regimen on day 8, and the dose of azathioprine was decreased (1.4 mg/kg PO q48h). On day 10, the platelet count increased to 48,000/mL and the dog was discharged from the hospital. Treatment at discharge included prednisone (1 mg/kg PO q12h), azathioprine (1.4 mg/kg PO q48h), cyclosporine (3.8 mg/kg PO q12h), and famotidine (0.5 mg/kg PO q12h).The dog was reevaluated on day 12 after initial presentation. Physical examination was unremarkable with resolution of petechiation and melena. A CBC revealed regenerative anemia (PCV, 22.8%; reticulocyte count, 210,900/mL; reference range 7,000-65,000/mL), mature neutrophilia (12,737/mL; reference range, 3,000-10,500 cells/mL), and a platelet count of 79,000/mL. A tro...

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Renal Transplantation

Adin¹

2011

Nephrology and Urology of Small Animals

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An Evaluation of Combined Immunosuppression with MNA 715 and Microemulsified Cyclosporine on Renal Allograft Rejection in Mismatched Mongrel Dogs

Abstract: An immunosuppressive regimen consisting of MNA715 and microemulsified cyclosporine may be effective in preventing allograft rejection in canine renal transplant patients.

Cited by 17 publications

References 42 publications

Immunosuppression with a combination of the leflunomide analog, FK778, and microemulsified cyclosporine for renal transplantation in mongrel dogs

Immunosuppression with a combination of the leflunomide analog, FK778, and microemulsified cyclosporine for renal transplantation in mongrel dogs

Ralstonia pickettiiSepticemia in a Dog with Immune‐Mediated Thrombocytopenia

Renal Transplantation

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