Effects of combination cyclosporine/mizoribine immunosuppression on canine renal allograft recipients.

Abstract:

:Heterotopic renal allografts following bilateral nephrectomies were placed in 21 healthy mongrel dogs. One group of 11 dogs received cyclosporine (5 mg/kg/24 hr, orally), and 1 group of 10 dogs received cyclosporine and mizoribine (5 mg/kg and 3 mg/kg/24 hr, orally). Body weights, blood cell counts, serum chemistry profiles, serum electrolyte levels, urinalysis with cytology and culture, lymphocyte stimulation assays, immunoglobulin levels, whole blood levels of cyclosporine, and serum levels of mizoribine were followed. At the end of each survival period, necropsy and histopathologic examinations were performed. The mean survival time for the cyclosporine group was 12.8 +/- 7 days. The mean survival time for the cyclosporine/mizoribine group was 33.6 +/- 16.4 days, significantly longer (P = .0006) than the cyclosporine group. Death in the cyclosporine/mizoribine group was attributed to the combined effects of renal allograft rejection and development of a mizoribine-dependent enteritis. Serum levels of mizoribine were greater in the last half of the survival period due to compromised renal excretion of the drug. There were no complications due to infection, myelosuppression, or hepatotoxicity. Combination cyclosporine/mizoribine immunosuppression enhanced canine renal allograft survival in this study. Monitoring serum concentrations of mizoribine is imperative to determine toxic (enteritis) levels. Availability of an intravenous form of mizoribine would facilitate immunoregulation during periods of variable intestinal absorption or renal excretion.

journal_name

Transplantation

journal_title

Transplantation

authors

Gregory CR,Gourley IM,Cain GR,Broaddus TW,Cowgill LD,Willits NH,Patz JD,Ishizaki G

doi

10.1097/00007890-198805000-00003

subject

Has Abstract

pub_date

1988-05-01 00:00:00

pages

856-9

issue

5

eissn

0041-1337

issn

1534-6080

journal_volume

45

pub_type

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