Holt D W, Marsden J T, Johnston A, Bewick M, Taube D H
Br Med J (Clin Res Ed). 1986 Oct 25;293(6554):1057-9. doi: 10.1136/bmj.293.6554.1057.
Forty nine renal allograft recipients taking oral cyclosporin suffered 76 episodes of renal dysfunction within six months of transplantation. These episodes were diagnosed as graft rejection or cyclosporin induced nephrotoxicity on the basis of histological findings in allograft biopsy specimens and the response to treatment. Mean predose blood cyclosporin concentrations measured by radioimmunoassay during the week before the onset of renal dysfunction were significantly higher when the cause was cyclosporin toxicity rather than graft rejection (392 v 741 nmol/l (471 v 891 ng/ml). During this period there was a significant association between both the frequency of measurements above 666 nmol/l (800 ng/ml) and the diagnosis of toxicity and the frequency of measurements below 333 nmol/l (400 ng/ml) and the diagnosis of allograft rejection. Cyclosporin measurements made at the time of biopsy and reference to the highest or lowest concentrations measured during the week preceding biopsy were of less value in distinguishing between the two groups. Despite lacking specificity for the parent compound, the radioimmunoassay used produced results which were of clinical value in optimising cyclosporin treatment.
49名接受口服环孢素治疗的肾移植受者在移植后6个月内出现了76次肾功能障碍发作。根据移植肾活检标本的组织学检查结果及对治疗的反应,这些发作被诊断为移植肾排斥反应或环孢素诱导的肾毒性。在肾功能障碍发作前一周,通过放射免疫测定法测得的环孢素给药前平均血药浓度,在病因是环孢素毒性而非移植肾排斥反应时显著更高(分别为392对741纳摩尔/升(471对891纳克/毫升))。在此期间,血药浓度高于666纳摩尔/升(800纳克/毫升)的测量频率与毒性诊断之间,以及血药浓度低于333纳摩尔/升(400纳克/毫升)的测量频率与移植肾排斥反应诊断之间均存在显著关联。在活检时进行的环孢素测量以及参考活检前一周测得的最高或最低浓度,在区分这两组时价值较小。尽管所用的放射免疫测定法对母体化合物缺乏特异性,但所产生的结果在优化环孢素治疗方面具有临床价值。