Trull A, Hue K, Tan K, Gore S, Whitewood S, Smyth R, Scott J, Price C, Wallwork J
Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, U.K.
Clin Chem. 1990 Aug;36(8 Pt 1):1474-8.
Cross-correlation of cyclosporine concentrations with results of biochemical tests of renal and liver function, measured during the first three months post-operatively, was carried out retrospectively in 24 heart and eight heart-lung transplant recipients to assess the temporal relationship between cyclosporine treatment and the development of possible toxic side-effects. We found a statistically significant negative correlation (95% confidence interval of the mean correlation coefficient did not overlap zero) between the five-day mean concentration of cyclosporine in whole blood (but not plasma) as measured with nonselective (NSRIA) and selective radioimmunoassays (SRIA) and the mean reciprocal creatinine concentration measured in the subsequent five days. In 15 of 32 (47%) patients the negative correlation coefficient exceeded 0.7 (high susceptibility), whereas in 11 of 32 (34%) it was between 0.5 and 0.7 (medium susceptibility), and in only six of 32 (19%) was it less than 0.3 (low susceptibility). We found no consistent correlations between cyclosporine measurements and results of other renal-function tests or liver-function tests. This suggests that therapeutic doses of the drug are not hepatotoxic in most patients. There was, however, a significantly correlated decrease in the NSRIA/SRIA ratio and in serum bilirubin concentration with time post-operatively, reflecting improvement in hepatic function and clearance of the cyclosporine metabolites that are detected by NSRIA. Assays of cyclosporine in whole blood, but not in plasma, are of value in anticipating changes in renal function after heart and heart-lung transplantation.
对24例心脏移植受者和8例心肺移植受者进行了回顾性研究，分析术后前三个月测定的环孢素浓度与肾和肝功能生化检测结果的交叉相关性，以评估环孢素治疗与可能的毒副作用发生之间的时间关系。我们发现，采用非选择性放射免疫分析法（NSRIA）和选择性放射免疫分析法（SRIA）测定的全血（而非血浆）中环孢素的五日平均浓度与随后五日测定的肌酐平均倒数浓度之间存在统计学显著的负相关（平均相关系数的95%置信区间不与零重叠）。在32例患者中的15例（47%）中，负相关系数超过0.7（高敏感性），而在32例中的11例（34%）中，负相关系数在0.5至0.7之间（中等敏感性），在32例中只有6例（19%）小于0.3（低敏感性）。我们未发现环孢素测量值与其他肾功能检测或肝功能检测结果之间存在一致的相关性。这表明该药物的治疗剂量在大多数患者中无肝毒性。然而，NSRIA/SRIA比值和血清胆红素浓度与术后时间呈显著相关下降，反映肝功能改善以及NSRIA检测到的环孢素代谢产物清除。全血中环孢素的检测，而非血浆中的检测，对于预测心脏和心肺移植后肾功能的变化具有价值。
