Cimetidine for kidney transplantation: experimental observations.

H2-histamine receptor antagonists may augment delayed hypersensitivity. The effect of cimetidine, a H2-histamine receptor antagonist, was assessed in renal allografts in dogs. The animals in the control group (I) (n = 5) received a renal transplant and moderate immunosuppression with azathioprine and prednisone. The dogs in the experimental group (II) (n = 8) were given cimetidine in two doses (300/150 mg, twice daily). Group III (n = 4) dogs were not operated upon and received all drugs in full dosage in order to test any direct toxic effect on normal kidneys. Biweekly gastric analysis, hemoglobin, white blood count, and daily serum creatinine were monitored. The dogs in group II that received the higher dose of cimetidine rejected the transplant earlier (mean survival, 20.4 days) than the dogs in the control group (mean survival, 37.8 days). No direct toxic effect from the drug was demonstrated in the control nontransplanted group. Cimetidine in high doses suppressed both basal and host stimulation secretion of gastric acid. In summary, the finding of increased rejection episodes and diminished survival after kidney transplantation in moderately immunosuppressed dogs that received cimetidine indicates that the use of this drug in transplantation is probably not safe until more is known about the immunological mechanisms involved in this situation.