Bolin Paul, Shihab Fuad S, Mulloy Laura, Henning Alice K, Gao Jeff, Bartucci Marilyn, Holman John, First M Roy
Division of Nephrology, Department of Medicine, East Carolina University, Greenville, NC, USA.
Transplantation. 2008 Jul 15;86(1):88-95. doi: 10.1097/TP.0b013e31817442cf.
The determination of optimal tacrolimus (TAC) trough levels is needed to prevent adverse effects of calcineurin inhibitors.
Stable transplant recipients currently receiving cyclosporine (CsA) were assigned randomly (1:1:1) to continue CsA (target trough level of 50-250 ng/mL); or convert to "reduced" TAC (target trough level 3.0-5.9 ng/mL) or "standard" TAC (target trough level 6.0-8.9 ng/mL).
At 12 months, there was a significant improvement in renal function in the reduced TAC versus CsA group with lower serum creatinine (P=0.004) and cystatin C (P<0.001), and higher estimated creatinine clearance (P=0.017). However, there were no statistically significant differences in any renal parameter in the standard TAC versus CsA group. Total and low-density lipoprotein cholesterol were significantly reduced in both TAC groups versus the CsA group (P<0.001). Patient and graft survival and episodes of biopsy-confirmed acute rejection were similar for all treatment groups, and no statistically significant differences were observed between groups in the incidence of new-onset diabetes or cardiac conditions, or in the prevalence of hyperglycemia, hypertension, or hyperlipidemia among patients who did not have these conditions at baseline. Alopecia developed more commonly among TAC-treated patients than CsA-treated patients (P<0.001).
Compared with CsA continuation, conversion to reduced TAC target trough concentrations resulted in significantly improved renal function without increasing the risk of rejection. Conversion to TAC, regardless of target concentration, resulted in improved serum lipid profiles in kidney transplant recipients at 12 months.
为预防钙调神经磷酸酶抑制剂的不良反应，需要确定他克莫司（TAC）的最佳谷浓度。
将目前正在接受环孢素（CsA）治疗的稳定移植受者随机（1:1:1）分配，继续使用CsA（目标谷浓度为50 - 250 ng/mL）；或转换为“低剂量”TAC（目标谷浓度3.0 - 5.9 ng/mL）或“标准剂量”TAC（目标谷浓度6.0 - 8.9 ng/mL）。
在12个月时，与CsA组相比，低剂量TAC组的肾功能有显著改善，血清肌酐（P = 0.004）和胱抑素C（P < 0.001）较低，估计肌酐清除率较高（P = 0.017）。然而，标准剂量TAC组与CsA组在任何肾脏参数上均无统计学显著差异。与CsA组相比，两个TAC组的总胆固醇和低密度脂蛋白胆固醇均显著降低（P < 0.001）。所有治疗组的患者和移植物存活率以及活检证实的急性排斥反应发生率相似，在新发糖尿病或心脏疾病的发生率方面，以及在基线时没有这些疾病的患者中高血糖、高血压或高脂血症的患病率方面，各组之间均未观察到统计学显著差异。TAC治疗的患者比CsA治疗的患者更常出现脱发（P < 0.001）。
与继续使用CsA相比，转换为低剂量TAC目标谷浓度可显著改善肾功能，而不增加排斥风险。无论目标浓度如何，转换为TAC均可使肾移植受者在12个月时的血脂谱得到改善。
