| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
1. Glucocorticoid Sensitivity in Peripheral-blood Lymphocytes of Chronic Renal Failure
Four glucocorticoids, hydrocortisone (Cor), prednisolone (PSL), methylprednisolone (MPSL), and dexamethasone (Dex) were examined for their ability to suppress in vitro blastogenesis of mitogen-stimulated peripheral lymphocytes obtained from 134 chronic renal failure (CRF) patients waiting for renal transplantation and 102 healthy volunteers. Lymphocyte response to each glucocorticoid showed wide deviations among the subjects. PSL IC_<50> values of the CRF patients showed the largest deviation ranging from 1.0 to 10,000ng/ml. Thus, a significantly large population of the CRF patients (25.4%) when compared with the healthy subjects (3.6%), showed a marked decrease in lymphocyte response to PSL (p<0.01). The anti-lymphocyte potency of PSL assessed by IC_<50> of the steroid was less than that of Cor, whereas MPSL was >12-fold superior to PSL.It is concluded that MPSL could be of benefit to PSL-resistrant
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recipients, who can be identified by the preperative lymphocyte culture.
2. Cyclosporine Sensitivity of Peripheral Blood Lymphocytes and Its Effect on Clinical Outcome in Renal Transplant Recipients.
We estimated individual circrosporin (CYA) sensitivity by determining CYA concentration that would give 50% suppression of preoperative lymphocyteblastogenesis in vitro (IC_<50>), and then relationship between CYA sensitivity and clinical outcome was investigated retrospectively. Venous blood was taken from 31 renal transplant patients (19 males and 12 females) before CYA administration. These patients were divided into two groups based on their lymphocyte sensitivity to CYA,i.e., low sensitive (LS) group (IC_<50> of CYA higher than 10ng/ml) and high sensitive (HS) group (IC_<50> of CYA less than 10ng/ml). We estimated clinical efficacy of CYA by investigating incidence of acute rejection episode and changes of serum creatinine concetraion (S-Cr). Mean numbers of acute rejection episode occurred in LS group were 2.25<plus-minus>1.88 times/patient while those in HS group were 1.16<plus-minus>1.27 times. Thus, the incidence of acute rejection episode was tended to be fewer in HS group, though there was no statistical significance in the incidence between the groups. The mean S-Cr level gradually increased in LS group during 18 months after operation. The mean S-Cr level in LS groups at 18 months after transplantation was 2.90<plus-minus>2.29mg/dl, which was significantly higher than that of HS group (1.72<plus-minus>2.16mg/dl) (p<0.02). It is suggested that individualized immunosuppressive therapy with CYA based on both of phamacokinetic and pharmacodynamic views could be performed by determining CYA through level and lymphocyte sensitivity to CYA in combination. Less
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