Effects of mizoribine on canine renal allograft recipients.
Heterotopic renal allograft transplantation and bilateral nephrectomies were performed on 12 mixed-breed dogs. Histoincompatibility was confirmed by serologically defined and lymphocyte-defined antigen testing. Mizoribine (5 mg/kg, q 24 h) was administered orally starting the day of surgery. Body weights, blood cell counts, serum biochemical and electrolyte values, immunoglobulin concentration, and serum mizoribine concentrations were determined. Complete urinalyses, including bacteriologic culturing and lymphocyte stimulation assays were performed. The mean survival time for the allograft recipients was 20 +/- 14 days; significantly longer than nontreated historic controls surviving 8.1 +/- 0.6 days (P = 0.0098). Death was attributed to the combined effects of renal allograft rejection and development of a mizoribine-dependent gastroenteritis. Serum mizoribine concentrations were greater in dogs undergoing rapid allograft rejection because of compromised renal excretion of the drug. This resulted in a rapid onset of gastroenteritis. There were no complications resulting from infection, myelosuppression, or hepatotoxicosis.
Gregory
C R
CR
Department of Surgery, School of Veterinary Medicine, University of California, Davis 95616.
Gourley
I M
IM
Haskins
S C
SC
Cain
G R
GR
Ishizaki
G
G
Cowgill
L D
LD
Willits
N H
NH
Patz
J D
JD
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D004283:Dog Diseases / Q000139:chemically induced / Q000473:pathology; D004285:Dogs / Q000601:surgery*; D004573:Electrolytes / Q000097:blood; D004906:Erythrocyte Count / Q000662:veterinary; D005260:Female; D005759:Gastroenteritis / Q000139:chemically induced / Q000473:pathology / Q000662:veterinary; D007136:Immunoglobulins / Q000032:analysis; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D008297:Male; D011183:Postoperative Complications / Q000473:pathology / Q000662:veterinary; D012263:Ribonucleosides / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D012709:Serum Albumin / Q000032:analysis; D012712:Serum Globulins / Q000032:analysis; D014184:Transplantation, Homologous; D014556:Urine / Q000032:analysis
D004573:Electrolytes; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D012263:Ribonucleosides; D012709:Serum Albumin; D012712:Serum Globulins; C010052:mizoribine; D003404:Creatinine; D000410:Alanine Transaminase