Kupin W L, Venkat K K, Norris C, Florence-Green D, Dienst S, Oh H K, Feldkamp C, Levin N W
Transplantation. 1987 Feb;43(2):214-8. doi: 10.1097/00007890-198702000-00010.
Nephrotoxicity and cost are the major problems in the use of cyclosporine (CsA) in renal transplantation. Thus, maintenance of CsA levels at the lower limits of the therapeutic range is desirable. The lowest CsA level effective in preventing rejection while avoiding nephrotoxicity has not been defined. We report on 44 primary cadaveric renal transplant recipients treated with a protocol that involved a progressive reduction in the trough CsA levels. CsA was initiated at an oral dose of 15 mg/kg, and this dose was adjusted to achieve serum trough levels, as measured by radioimmunoassay, of 150-200 ng/ml during the first month, 100-150 ng/ml during the second month, 75-100 ng/ml during the third month, and 50-75 ng/ml thereafter. Patient and graft survival at 18 months were 94% and 83.6%, respectively. The mean daily CsA doses were 6.7 +/- 3.1 mg/kg at 6 months, 5.5 +/- 3.2 mg/kg at 12 months, and 4.7 +/- 2.4 mg/kg at 18 months. Corresponding trough serum CsA levels were 94 +/- 59 ng/ml, 64 +/- 22 ng/ml, and 44 +/- 21 ng/ml at 6, 12, and 18 months, respectively. Mean serum creatinine concentrations were 1.8 +/- 0.6 mg/dl at 6 months, 1.7 +/- 0.5 mg/dl at 12 months, and 1.6 +/- 0.5 mg/dl at 18 months. The mean serum creatinine concentration at 18 months was not significantly different from that of 18 conventionally treated primary cadaveric renal transplant recipients (1.6 +/- 0.5 vs. 1.4 +/- 0.4 mg/dl, P = .31). A total of 67% of patients did not have any rejection episodes under this protocol, while 71% of patients never developed CsA nephrotoxicity. No patient was taken off CsA for progressive nephrotoxicity. We conclude that trough serum CsA levels of 50-75 ng/ml, as measured by radioimmunoassay, are sufficient to maintain effective immunosuppression in the long-term management of primary cadaveric renal transplant recipients. These values are much lower than previously recommended, and this approach ameliorates chronic CsA nephrotoxicity.
肾毒性和成本是肾移植中使用环孢素（CsA）的主要问题。因此，将CsA水平维持在治疗范围的下限是可取的。在避免肾毒性的同时有效预防排斥反应的最低CsA水平尚未确定。我们报告了44例接受原发性尸体肾移植的受者，他们采用了一种逐步降低CsA谷值水平的方案进行治疗。CsA开始时口服剂量为15mg/kg，并根据放射免疫测定法进行调整，以使血清谷值水平在第一个月达到150 - 200ng/ml，第二个月达到100 - 150ng/ml，第三个月达到75 - 100ng/ml，此后达到50 - 75ng/ml。18个月时患者和移植物的存活率分别为94%和83.6%。6个月时CsA的平均每日剂量为6.7±3.1mg/kg，12个月时为5.5±3.2mg/kg，18个月时为4.7±2.4mg/kg。6、12和18个月时相应的血清CsA谷值水平分别为94±59ng/ml、64±22ng/ml和44±21ng/ml。6个月时血清肌酐平均浓度为1.8±0.6mg/dl，12个月时为1.7±0.5mg/dl，18个月时为1.6±0.5mg/dl。18个月时的血清肌酐平均浓度与18例接受传统治疗的原发性尸体肾移植受者相比无显著差异（1.6±0.5与1.4±0.4mg/dl，P = 0.31）。在该方案下，共有67%的患者未发生任何排斥反应，而71%的患者从未发生CsA肾毒性。没有患者因进行性肾毒性而停用CsA。我们得出结论，通过放射免疫测定法测得的血清CsA谷值水平为50 - 75ng/ml足以在原发性尸体肾移植受者的长期管理中维持有效的免疫抑制。这些值远低于先前推荐的值，并且这种方法改善了慢性CsA肾毒性。
