McDiarmid S V, Colonna J O, Shaked A, Ament M E, Busuttil R W
Department of Surgery, UCLA.
Transplantation. 1993 Oct;56(4):847-53. doi: 10.1097/00007890-199310000-00014.
In this randomized controlled trial comparing FK-506 to CsA, we report parameters of nephrotoxicity in adult patients surviving > 90 days after orthotopic liver transplant (OLT). Patients randomized to FK-506 first received 0.15 mg/kg IV/day followed by 0.3 mg/kg PO/day. Doses were modified to avoid toxicity and to achieve FK-506 levels of 0.5 to 1.5 ng/ml. CsA was administered in the usual manner with dose adjustments to whole blood HPLC levels. A pre-OLT glomerular filtration rate (GFR) of > or = 30 ml/min/1.73/m2 and/or serum creatinine < or = 2.0 mg/dl were required for inclusion in the study. GFRs were obtained at post OLT days 28, 180, and 360. Other parameters of renal function evaluated were creatinine, magnesium, serum electrolytes, blood pressure, use of antihypertensives, and magnesium supplements. There were 38 patients in the FK-506 group and 34 in the CsA group. The mean days of follow up for each group was similar: 456 +/- 135 days for the FK-506 group and 451 +/- 112 days for the CsA group. The mean oral dose for the FK-506 group ranged from 0.13-0.16 mg/kg/day with mean FK-506 levels of 0.6-0.8 ng/ml. In the FK-506 group, there was a significant fall in the pre-transplant GFR from 89 +/- 31 ml/min/173 m2 to 43 +/- 15 ml/min/173 m2 at day 360. Similarly, for the CsA group, the pre-transplant GFR of 75 +/- 31 ml/min/1.73 m2 fell to 49 +/- 17 ml/min/1.73 m2 at day 360. At each time point studied, there was no significant difference in mean GFR between the two groups. There were no significant differences in the monthly mean values for creatinine, electrolytes, magnesium, or blood pressure between the two groups. Magnesium levels were in the low normal range (1.4-1.6 mEq/L), and the mean potassium levels in the high normal range (4.4-4.7 mEq/L). In both groups, a similar number of patients required magnesium supplementation or hypertensive medications. The nephrotoxicity of FK-506 given at low oral doses and with concomitant low levels was comparable to that of CsA. The two drugs were remarkably similar in their spectrum of electrolyte disturbances and incidence of hypertension.
在这项比较FK-506与环孢素A（CsA）的随机对照试验中，我们报告了原位肝移植（OLT）术后存活超过90天的成年患者的肾毒性参数。随机分配至FK-506组的患者首先静脉注射0.15mg/kg/天，随后口服0.3mg/kg/天。调整剂量以避免毒性并使FK-506水平达到0.5至1.5ng/ml。CsA以常规方式给药，并根据全血高效液相色谱（HPLC）水平调整剂量。纳入研究要求OLT术前肾小球滤过率（GFR）≥30ml/min/1.73/m²和/或血清肌酐≤2.0mg/dl。在OLT术后第28、180和360天测定GFR。评估的其他肾功能参数包括肌酐、镁、血清电解质、血压、抗高血压药物的使用以及镁补充剂的使用。FK-506组有38例患者，CsA组有34例患者。每组的平均随访天数相似：FK-506组为456±135天，CsA组为451±112天。FK-506组的平均口服剂量范围为0.13 - 0.16mg/kg/天，FK-506平均水平为0.6 - 0.8ng/ml。在FK-506组，移植前GFR在第360天从89±31ml/min/1.73m²显著下降至43±15ml/min/1.73m²。同样，CsA组移植前GFR为75±31ml/min/1.73m²，在第360天降至49±17ml/min/1.73m²。在每个研究时间点，两组的平均GFR无显著差异。两组之间肌酐、电解质、镁或血压的月度平均值无显著差异。镁水平处于低正常范围（1.4 - 1.6mEq/L），平均钾水平处于高正常范围（4.4 - 4.7mEq/L）。两组中需要补充镁或使用抗高血压药物的患者数量相似。低口服剂量并伴有低水平的FK-506的肾毒性与CsA相当。这两种药物在电解质紊乱谱和高血压发生率方面非常相似。
