INHIBITION OF THE REJECTION OF RENAL HOMOGRAFTS IN DOGS BY DRUGS

Journal Article · Wed May 01 00:00:00 EDT 1963 · Ann. Roy. Coll. Surg. Engl.

OSTI ID:4058461

Calne, R Y

The use of cytostntic drugs and whole-body irradiation to reduce the immunologic response to kidney transplantation is reported. In the absence of such trentments, canine renal transplarts usually cease to function 5 to 8 days after operation, although occasionally a transplant will function for 14 days. To prevent rejection of homologous tissue, a very high dose of x rays is necessary. To inhibit renal homograft rejection experimentally, it is necessary to destroy the hematopoietic tissue in the bone marrow. Thus, below 1000-r doses of total-body x irradiation, typical rejection occurs, while above 1300 r rejection is inhibited, but only one of the dogs studied survived more than a few days. The use of thiopurines and other drugs was compared with sublethal whole- body irradiation for effectiveness in prolonging homologous kidney grafts in dogs. The percentages of dogs (104 were studied) surviving beyond 3 months after bilateral renal homografts and treated with x rays, 6-mercaptopurine, nitrogen mustard, cyclophosphamide, Actinomycin D, Actinomycin C were 8, 0, 17, 0, 20, and 25%, respectively. The respective mean survival times with these treatments were 34, 22, 32, 16, 28, and 58 days. When the 104 animals from all groups are considered, only 10% survived beyond 3 months. This marked variability could be attributed to one or a combination of the following: variability of the aggressiveness of immune reaction in different animals; alternative pathways of purine metabolism that can bypass the specific blocks of the purine analogs; variability in absorption and excretion of the drugs; chance relation of histocompatibility factors between random outbred dogs. The significance of these results for human kidney grafting is discussed. Of the various methods of preventing renal homograft rejection discussed, thiopurine drugs appear to be the only agents that have a repeatable effect on adult animals and the lethal effect of irradiation above 1300 r precludes the use of such a dose clinically. (BBB)

• Research Organization: Westminster Medical School, London
• NSA Number: NSA-18-017495
• OSTI ID: 4058461
• Journal Information: Ann. Roy. Coll. Surg. Engl., Vol. Vol: 32; Other Information: Orig. Receipt Date: 31-DEC-64
• Country of Publication: Country unknown/Code not available
• Language: English

Related Subjects

BIOLOGY AND MEDICINE
ACTINOMYCIN
AMIDES
ANTIBIOTICS
ANTIMITOTIC DRUGS
BIOCHEMISTRY
BLOOD FORMATION
BODY
BONE MARROW
CYTOLOGY
DIFFUSION
DISTRIBUTION
DOGS
DRUGS
EFFICIENCY
HETEROCYCLICS
IMMUNITY
IRRADIATION
KIDNEYS
LETHAL DOSE
MEDICINE
METABOLISM
NITROGEN MUSTARD
NUMERICALS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PHOSPHORIC ACID
PHYSIOLOGY
PURINES
QUANTITY RATIO
RADIATION DOSES
RADIATION INJURIES
SAFETY
SENSITIVITY
STATISTICS
SURGERY
SURVIVAL TIME
TISSUES
TOXICITY
TRANSPLANTS
VARIATIONS
X RADIATION