title: Steroid withdrawal based on lymphocyte sensitivity to endogenous steroid in renal transplant recipients.
abstract: Though steroid withdrawal is done in many renal transplant recipients, some patients must restart steroids. Little report has investigated steroid withdrawal under pharmacodynamic monitoring. We assessed lymphocyte sensitivity to endogenous cortisol as a biomarker for determining the safety of steroid withdrawal in renal transplant patients, as we hypothesized that patients hyposensitive to cortisol could not be sufficiently immunosuppressed by their intrinsic cortisol as a substitute for the reduced or withdrawn steroid. Lymphocyte sensitivity to cortisol was examined in 30 long stable renal transplant recipients. Lymphocyte sensitivity to cortisol and its relationship with the clinical outcome after steroid reduction and withdrawal was investigated. The lymphocyte sensitivities to cortisol were estimated as IC(50) of lymphocyte blastogenesis. The lymphocyte proliferation rate for concentration of serum cortisol compared between incident and non-incident groups. Serum creatinine levels (S-Cr) increased in a significantly higher number of patients hyposensitive to cortisol (IC(50)≧10000 ng/ml) than in normally sensitive patients (IC(50)<10000 ng/ml). The incidences of steroid withdrawal syndrome and necessity for increasing steroid dose or restarting steroid administration were also higher in the patients hyposensitive to cortisol. The patients in whom the lymphocyte proliferation rate was less than 60% did not show increase in S-Cr, experience steroid withdrawal symptoms, or require an increase in the steroid dose or restart of steroid administration. The patients who have the normal IC(50) values of cortisol, can withdraw steroid more safely. The lymphocyte sensitivity to cortisol may be a useful biomarker for selecting patients who can sustain steroid withdrawal.
authors.affiliation: Department of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences, Japan. take@toyaku.ac.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Naoto
authors.initials: N
authors.lastname: Matsuno
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
authors.forename: Muhetaer
authors.initials: M
authors.lastname: Gulimire
authors.forename: Koichiro
authors.initials: K
authors.lastname: Hama
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Iwamoto
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Toraishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Okuyama
authors.forename: Sakae
authors.initials: S
authors.lastname: Unezaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagao
mesh_terms: D000305:Adrenal Cortex Hormones; D000328:Adult; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D016572:Cyclosporine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000097:blood / Q000502:physiology*; D007165:Immunosuppression Therapy / Q000706:statistics & numerical data; D007166:Immunosuppressive Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000379:methods / Q000502:physiology*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects; D013256:Steroids / Q000008:administration & dosage / Q000494:pharmacology; D016559:Tacrolimus / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones; D054316:Biomarkers, Pharmacological; D007166:Immunosuppressive Agents; D011956:Receptors, Cell Surface; D013256:Steroids; D016572:Cyclosporine; D011239:Prednisolone; D006854:Hydrocortisone; D016559:Tacrolimus; D008775:Methylprednisolone