Taler S J, Textor S C, Canzanello V J, Schwartz L, Porayko M, Wiesner R H, Krom R A
Division of Hypertension, Mayo Clinic, Rochester, Minnesota 55905, USA.
Transplantation. 1996 Dec 15;62(11):1588-92. doi: 10.1097/00007890-199612150-00011.
Transplant immunosuppression using either cyclosporine (CsA) or tacrolimus (FK506) leads to renal vasoconstriction and nephrotoxicity. Despite producing similar effects within the kidney and blood vessels, clinical hypertension occurs less frequently with tacrolimus during the first year after transplantation, compared with CsA. To examine the role of steroid dose in early posttransplant hypertension, we measured blood pressure and kidney function in liver transplant recipients treated with tacrolimus and either high-dose (TAC-HI-P, n = 19) or low-dose (TAC-LO-P,n = 20) prednisone, compared with CsA-treated recipients (n = 29) receiving prednisone doses similar to the TAC-HI-P group. At 1 month, hypertension occurred more often with CsA (72%) than with TAC-HI-P (42%, P < 0.05) or TAC-LO-P (30%, P < 0.05). By 4 months after transplantation, hypertension developed in nearly twice as many TAC-HI-P (63%) as TAC-LO-P patients (32%, P < 0.05), with no difference between TAC-HI-P and CsA (86%, NS). Daily prednisone dose at 1 month closely paralleled cumulative steroid dose in the first month in the TAC-HI-P and TAC-LO-P groups. Fourteen of 19 TAC-HI-P patients (74%) required bolus steroids for treatment of rejection within the first month, compared with 3/20 (15%) TAC-LO-P and 10/29 (34%) CsA recipients. Glomerular filtration rate fell from pretransplant levels at 1 month and 4 months to the same degree in CsA, TAC-HI-P, and TAC-LO-P patients. These results demonstrate a central role for steroid dose in the rate of onset of hypertension early after liver transplantation using tacrolimus immunosuppression. Both daily dose and cumulative dosage, including bolus treatment for rejection, may impact on the development of hypertension. Since prevalence rates rise to levels comparable to CsA by 24 months regardless of steroid dose, hypertension after liver transplant may be mediated by different mechanisms at different stages of the posttransplant course.
使用环孢素（CsA）或他克莫司（FK506）进行移植免疫抑制会导致肾血管收缩和肾毒性。尽管在肾脏和血管内产生相似的效应，但与CsA相比，移植后第一年他克莫司导致临床高血压的情况较少见。为了研究类固醇剂量在移植后早期高血压中的作用，我们测量了接受他克莫司和高剂量（TAC-HI-P，n = 19）或低剂量（TAC-LO-P，n = 20）泼尼松治疗的肝移植受者的血压和肾功能，并与接受与TAC-HI-P组相似泼尼松剂量的CsA治疗受者（n = 29）进行比较。在1个月时，CsA组高血压发生率（72%）高于TAC-HI-P组（42%，P < 0.05）或TAC-LO-P组（30%，P < 0.05）。移植后4个月时，TAC-HI-P组高血压发生率（63%）几乎是TAC-LO-P组患者（32%，P < 0.05）的两倍，TAC-HI-P组与CsA组（86%，无显著性差异）之间无差异。在TAC-HI-P组和TAC-LO-P组中，1个月时的每日泼尼松剂量与第一个月的累积类固醇剂量密切相关。19例TAC-HI-P患者中有14例（74%）在第一个月内需要大剂量类固醇治疗排斥反应，相比之下，TAC-LO-P组为3/20（15%），CsA组为10/29（34%）。在CsA组、TAC-HI-P组和TAC-LO-P组患者中，肾小球滤过率在1个月和4个月时从移植前水平下降到相同程度。这些结果表明，在使用他克莫司免疫抑制的肝移植后早期，类固醇剂量在高血压发病速率中起核心作用。每日剂量和累积剂量，包括用于治疗排斥反应的大剂量治疗，都可能影响高血压的发生。由于无论类固醇剂量如何，24个月时高血压患病率都会上升到与CsA相当的水平，肝移植后的高血压可能在移植后病程的不同阶段由不同机制介导。
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