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- Title
Lymphocyte-sensitivity to glucocorticoid correlates with the sensitivity to cyclosporin A and tacrolimus in chronic renal failure patients.
- Authors
Horigome; Hirano; Oka; Takeuchi; Sakurai; Kozaki; Matsuno; Nagao
- Abstract
Aims Association between lymphocyte-sensitivity to immunosuppressants in transplant recipients in vitro and clinical outcomes has been demonstrated. In general, renal transplant recipients are treated with a combination of immunosuppressants such as either glucocorticoid/cyclosporin A (CsA) or glucocorticoid/tacrolimus (FK506) but the pharmacological complementarity of these drugs is still controversial. We examined relationships between the lymphocyte-sensitivities to these immunosuppressants. Methods We examined lymphocyte-sensitivities to prednisolone (PSL), CsA, and FK506 in vitro in a total of 190 chronic renal failure (CRF) patients and 140 healthy subjects. The lymphocyte-sensitivity was evaluated from the IC[sub 50] value against mitogen-stimulated lymphocyte-blastogenesis in vitro. Results Statistically significant correlations of the IC[sub 50] values in CRF patients between the following pairs of drugs were observed: PSL and CsA (P<0.0001; n=129, r=0.419), PSL and FK506 (P<0.001; n=54, r=0.441), and CsA and FK506 (P<0.0001; n=45, r=0.608).Similar correlations were also observed in lymphocytes from healthy subjects. The population of CRF patients who exhibited high IC[sub 50] values (low sensitivities) to PSL and FK506 was significantly larger than that of healthy subjects (P<0.05). Conclusions Patients who showed low lymphocyte-sensitivity to either of the drugs also may exhibit low sensitivity to the others, and thus they may have a high risk of unsatisfactory outcome under combination therapy after renal transplantation. To overcome this risk, the selection of immunosuppressants is recommended to be restricted according to individual lymphocyte-sensitivities to these drugs in vitro, or alternatively, by addition of other drugs with different mechanisms for immunosuppression.
- Subjects
LYMPHOCYTE metabolism; GLUCOCORTICOIDS; CYCLOSPORINE; CHRONIC kidney failure; DRUG side effects; DIAGNOSIS
- Publication
British Journal of Clinical Pharmacology, 1999, Vol 48, Issue 4
- ISSN
0306-5251
- Publication type
Article