Centre for Pharmacology and Toxicology, Hannover Medical School, Germany.
Department of General, Visceral and Transplant Surgery, Hannover Medical School, Germany.
Vascul Pharmacol. 2019 Apr;115:69-83. doi: 10.1016/j.vph.2018.06.012. Epub 2018 Jun 19.
Post-transplant hypertension (PTH) is a common complication in cyclosporine immunosuppressed patients; however choosing the right antihypertensive medication is challenging. In a long-term observational study (≤13y) we examined different antihypertensive medications on graft/patient survival of kidney recipients with pre-existing and PTH. Altogether thirty-three co-variables were analyzed including dose and type of immunosuppressive and antihypertensive medication, co-medications, serum biochemistries and the glomerular filtration rate (GFR). A Cox proportional-hazard multivariable survival model was developed to detect a Hazard Ratio (HR) of 3.0 at the Bonferroni corrected level α = 0.0015. Importantly, a significant relationship between immunosuppressive cyclosporine dose/serum concentration, systolic blood pressure (SBP) and GFR (p < 0.001) was observed with post-transplant hypertension being a major risk factor (HR6.1) for graft/patient survival. Although all medications lowered effectively elevated SBP the risk of graft failure/death was significantly increased when hypertension was treated with ACE inhibitors or β-blockers (HR3.3 and 3.1) but not with angiotensin receptor- and/or Ca-channel blockers. Antihypertensive medication was associated with a decline in GFR but β-blockers alone or in combination with ARB and/or CCB improved GFR. Neither BMI nor any of the drug combinations used in immunosuppression, i.e. prednisolone, mycophenolic acid, azathioprine and/or sirolimus influenced patient and/or graft survival while decision tree analyses informed on complex dependencies between immunosuppressive medications, dose of anti-hypertensive drug and diuretics in the management of hypertension. In conclusion, our study is suggestive for graft/patient survival to be influenced by the class of antihypertensive medication. A prospective randomized clinical trial is needed to confirm the results.
移植后高血压（PTH）是环孢素免疫抑制患者的常见并发症；然而，选择合适的降压药物具有挑战性。在一项长期观察研究（≤13 年）中，我们研究了患有既往和 PTH 的肾移植受者的不同降压药物对移植物/患者存活率的影响。共分析了 33 个协变量，包括免疫抑制和降压药物的剂量和类型、合并用药、血清生化和肾小球滤过率（GFR）。开发了 Cox 比例风险多变量生存模型，以检测 Bonferroni 校正水平 α = 0.0015 的风险比（HR）为 3.0。重要的是，观察到环孢素免疫抑制剂量/血清浓度、收缩压（SBP）和 GFR 之间存在显著的相关性（p < 0.001），移植后高血压是移植物/患者存活率的主要危险因素（HR6.1）。尽管所有药物都有效降低了升高的 SBP，但当高血压用 ACE 抑制剂或β受体阻滞剂治疗时，移植失败/死亡的风险显著增加（HR3.3 和 3.1），而血管紧张素受体和/或钙通道阻滞剂则不然。降压药物与 GFR 下降相关，但β受体阻滞剂单独或与 ARB 和/或 CCB 联合使用可改善 GFR。BMI 或免疫抑制中使用的任何药物组合，即泼尼松、霉酚酸酯、硫唑嘌呤和/或西罗莫司，都不影响患者和/或移植物存活率，而决策树分析则提供了关于免疫抑制药物、降压药物剂量和利尿剂在高血压管理中的复杂依赖性的信息。总之，我们的研究提示降压药物的种类会影响移植物/患者的存活率。需要进行前瞻性随机临床试验来证实这些结果。
