Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Allergy. 2010 Nov;65(11):1381-7. doi: 10.1111/j.1398-9995.2010.02398.x.
Immunosuppressants decrease circulating dipeptidyl peptidase IV (DPPIV) activity in transplant patients, and decreased DPPIV activity has been associated with angiotensin-converting enzyme (ACE) inhibitor-associated angioedema. One study has reported an increased incidence of ACE inhibitor-associated angioedema among transplant patients compared to published rates, while several case series report angioedema in patients taking specific immunosuppressant agents.
To test the hypothesis that transplant patients are at increased risk of ACE inhibitor-associated angioedema.
We assessed the proportion of transplant patients in 145 cases with ACE inhibitor-associated angioedema and 280 ACE inhibitor-exposed controls. We measured the relationship between case-control status, transplant status, and immunosuppressant use and circulating DPPIV activity. We also assessed the incidence of angioedema among consecutive patients who underwent renal or cardiac transplant and were treated with an ACE inhibitor.
Transplant patients were significantly overrepresented among ACE inhibitor-associated angioedema cases compared to controls (odds ratio 18.5, 95% CI 2.3-147.2, P = 0.0004). Immunosuppressant use, chronic renal failure, seasonal allergies and smoking were also associated with ACE inhibitor-associated angioedema in univariate analysis. The association of transplant status with ACE inhibitor-associated angioedema was no longer significant after inclusion of immunosuppressant therapy in a multivariate analysis. Dipeptidyl peptidase IV activity was significantly decreased in sera from cases compared to ACE inhibitor-exposed controls, as well as in individuals taking immunosuppressants. Two of 47 ACE inhibitor-treated renal transplant patients and one of 36 ACE inhibitor-treated cardiac transplant patients developed angioedema.
Transplant patients are at increased risk of ACE inhibitor-associated angioedema possibly because of the effects of immunosuppressants on the activity of DPPIV.
免疫抑制剂会降低移植患者循环中二肽基肽酶 IV（DPPIV）的活性，而 DPPIV 活性降低与血管紧张素转换酶（ACE）抑制剂相关的血管性水肿有关。一项研究报告称，与已发表的发生率相比，移植患者中 ACE 抑制剂相关血管性水肿的发生率增加，而几项病例系列报告称，服用特定免疫抑制剂的患者发生血管性水肿。
检验移植患者 ACE 抑制剂相关血管性水肿风险增加的假设。
我们评估了 145 例 ACE 抑制剂相关血管性水肿病例和 280 例 ACE 抑制剂暴露对照者中移植患者的比例。我们测量了病例对照状态、移植状态与免疫抑制剂使用和循环 DPPIV 活性之间的关系。我们还评估了连续接受肾或心脏移植并接受 ACE 抑制剂治疗的患者中血管性水肿的发生率。
与对照组相比，ACE 抑制剂相关血管性水肿病例中移植患者的比例明显更高（比值比 18.5，95%置信区间 2.3-147.2，P = 0.0004）。在单变量分析中，免疫抑制剂使用、慢性肾衰竭、季节性过敏和吸烟也与 ACE 抑制剂相关血管性水肿有关。在多变量分析中纳入免疫抑制剂治疗后，移植状态与 ACE 抑制剂相关血管性水肿的相关性不再显著。与 ACE 抑制剂暴露对照者相比，ACE 抑制剂相关血管性水肿病例的血清中二肽基肽酶 IV 活性明显降低，且在服用免疫抑制剂的个体中也降低。47 例接受 ACE 抑制剂治疗的肾移植患者中有 2 例和 36 例接受 ACE 抑制剂治疗的心脏移植患者中有 1 例发生血管性水肿。
移植患者 ACE 抑制剂相关血管性水肿的风险增加，可能是因为免疫抑制剂对 DPPIV 活性的影响。
