Sijpkens Y W, Mallat M J, Siegert C E, Zwinderman A H, Westendorp R G, de Fijter J W, van Es L A, Paul L C
Department of Nephrology, Leiden University Medical Center, The Netherlands.
Clin Nephrol. 2001 Feb;55(2):149-55.
In 1995 - 1996, we switched from a once-daily Sandimmune dose to a twice-daily dose regimen of Neoral. Concurrent with the switch we changed our target trough level from 100 microg/l at 24 hours to the generally accepted 12-hour level of 150 microg/l. We performed a retrospective cohort study to assess cyclosporine toxicity following this switch and to identify risk factors for nephrotoxicity.
Of 212 patients with a stable graft function pre-conversion clinical parameters at 1 and 12 months post-conversion were compared with those at time of conversion. Cyclosporine nephrotoxicity was defined as a significant decline of the reciprocal of the serum creatinine concentration over time post-conversion in the absence of other obvious causes for declining graft function. Risk factors of cyclosporine nephrotoxicity were assessed using logistic regression analysis.
The mean cyclosporine trough level rose from 87 microg/l at the time of conversion to 139 microg/l at 12 months post-conversion whereas the daily drug dose increased over the same period from 233 mg to 252 mg. Mean serum creatinine increased by 10% from 135 to 148 micromol/l (p < 0.001). Cyclosporine nephrotoxicity was present in 42 patients (20%). Cyclosporine dose and trough level did not predict nephrotoxicity but beta-blockers (OR 0.35, 95% CI 0.17-0.72) and calcium channel blockers (OR 0.35, 95% CI 0.19-0.82) reduced the risk of nephrotoxicity, independent from an effect on blood pressure.
20% of stable renal transplant patients experienced chronic cyclosporine nephrotoxicity after conversion from a once-daily Sandimmune regimen to a twice-daily Neoral regimen with dose adjustments to a trough level of 150 microg/l. beta-blockers and calcium channel blockers reduced the risk of nephrotoxicity.
1995 - 1996年期间，我们将山地明的每日一次给药方案改为新山地明的每日两次给药方案。在方案转换的同时，我们将目标谷浓度从24小时的100微克/升改为普遍认可的12小时的150微克/升。我们进行了一项回顾性队列研究，以评估此次方案转换后环孢素的毒性，并确定肾毒性的危险因素。
在212例转换前移植肾功能稳定的患者中，将转换后1个月和12个月时的临床参数与转换时的参数进行比较。环孢素肾毒性定义为在转换后，血清肌酐浓度倒数随时间显著下降，且不存在移植肾功能下降的其他明显原因。使用逻辑回归分析评估环孢素肾毒性的危险因素。
环孢素的平均谷浓度从转换时的87微克/升升至转换后12个月时的139微克/升，而同期每日药物剂量从233毫克增加至252毫克。平均血清肌酐从135微摩尔/升增加10%至148微摩尔/升（p < 0.001）。42例患者（20%）出现环孢素肾毒性。环孢素剂量和谷浓度不能预测肾毒性，但β受体阻滞剂（比值比0.35，95%可信区间0.17 - 0.72）和钙通道阻滞剂（比值比0.35，95%可信区间0.19 - 0.82）可降低肾毒性风险，且与对血压的影响无关。
20%移植肾功能稳定的肾移植患者，在从山地明每日一次给药方案转换为新山地明每日两次给药方案并将剂量调整至谷浓度150微克/升后，出现了慢性环孢素肾毒性。β受体阻滞剂和钙通道阻滞剂可降低肾毒性风险。
