Comparison of adrenal functions in kidney transplant recipients with different long-term immunosuppressive treatments--prednisolone and azathioprine versus prednisolone and cyclosporine.
Adverse effects of cyclosporine on the adrenal cortex have been documented in animal experiments, but nothing has been reported in human subjects. Endogenous cortisol in peripheral blood was monitored for three years after transplantation, with 30 kidney recipients on two different immunosuppressive treatments. In the azathioprine group, 16 patients were treated with coadministration of prednisolone at an initial dose of 120 mg/day. In the cyclosporine group, 14 patients were also treated with prednisolone, using an initial dose of 60 mg per day. Short ACTH stimulation tests were performed to reconfirm the results obtained by basal cortisol monitoring. During the first year following transplant, cortisol concentrations in the cyclosporine group were higher, though not significantly so, than those in the azathioprine group, in accordance with cumulative amounts of prednisolone administered. At three years, however, the mean cortisol concentrations in the azathioprine group were 2-3 times higher than those in the cyclosporine group (P < 0.05). All patients in the azathioprine group responded well to ACTH, whereas 4 patients out of 14 in the cyclosporine group showed continuous severe suppression without considerable response to ACTH (P < 0.01). In conclusion, we would like to suggest that adrenocortical toxicity of long-term cyclosporine use may appear one year after transplant, resulting in chronic suppression of the adrenal cortex, and, accordingly, difficulty in further reduction of prednisolone use.
Oka
K
K
Division of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.
Shimodaira
H
H
Hirano
T
T
Sakurai
E
E
Tamaki
T
T
Kozaki
M
M
D000311:Adrenal Glands / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000502:physiology; D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004702:Endocrine Glands / Q000187:drug effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000502:physiology; D007674:Kidney Diseases / Q000139:chemically induced; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced; D011014:Pneumonia / Q000139:chemically induced; D011239:Prednisolone / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000324:Adrenocorticotropic Hormone; D011239:Prednisolone; D001379:Azathioprine; D006854:Hydrocortisone