Gossmann J, Thürmann P, Bachmann T, Weller S, Kachel H G, Schoeppe W, Scheuermann E H
Abt. f. Nephrologie, Johann Wolfgang Goethe-Universität, Frankfurt/Main, Germany.
Kidney Int. 1996 Sep;50(3):973-8. doi: 10.1038/ki.1996.398.
To delineate the pathogenesis of the reduction in hemoglobin occurring in renal transplant patients treated with angiotensin converting enzyme inhibitors (ACEI) and azathioprine (AZA) a controlled, prospective trial of ACEI withdrawal was conducted. The ACEI was replaced by nifedipine or clonidine in 15 kidney transplant patients immunosuppressed with AZA and prednisone (enalapril in 14 and captopril in 1). Before and during 10 to 12 weeks after withdrawal of the ACEI, AZA metabolites, renal function parameters and hematological parameters including erythropoietin and reticulocytes were evaluated. Enalaprilat levels were measured and compared with 15 similar patients matched for transplant function and enalapril dosage immunosuppressed with cyclosporine and prednisone. AZA metabolites did not differ significantly in the presence or absence of the ACEI. Enalaprilat levels also showed no significant difference between the two patient groups treated with AZA or cyclosporine. Hematocrit and hemoglobin increased significantly from 37.5 +/- 6.4 to 39.7 +/- 3.6% (mean +/- SD, P = 0.02) and 12.8 +/- 2.2 to 13.5 +/- 1.2 g/dl, P = 0.04, respectively, 10 to 12 weeks after ACEI treatment had been discontinued. Simultaneously numbers of reticulocytes and erythropoietin concentrations rose significantly after 2, 4 and 10 weeks, with a peak at two weeks (from 14.1 +/- 3.8 to 20.6 +/- 8.0/1000, P < 0.05 and from 14.3 +/- 12.4 to 29.3 +/- 54.5 mU/ml, P < 0.05, respectively). In conclusion, ACEI-related anemia in renal transplant recipients seems to be due to the erythropoietin-lowering effect of this group of drugs. A pharmacokinetic interaction between AZA and enalapril is not likely since plasma enalaprilat levels were independent of the immunosuppressive regimen and AZA metabolite levels were unchanged in the presence and absence of the ACEI. Several mechanisms by which angiotensin converting enzyme blockade may cause a decrease in circulating erythropoietin are discussed.
为了阐明接受血管紧张素转换酶抑制剂（ACEI）和硫唑嘌呤（AZA）治疗的肾移植患者血红蛋白降低的发病机制，我们进行了一项关于停用ACEI的对照前瞻性试验。15例接受AZA和泼尼松免疫抑制治疗的肾移植患者（14例使用依那普利，1例使用卡托普利），将ACEI换成硝苯地平或可乐定。在停用ACEI后的10至12周内，评估AZA代谢产物、肾功能参数以及包括促红细胞生成素和网织红细胞在内的血液学参数。测量依那普利拉水平，并与15例移植功能和依那普利剂量匹配、接受环孢素和泼尼松免疫抑制治疗的类似患者进行比较。无论有无ACEI，AZA代谢产物均无显著差异。两组接受AZA或环孢素治疗的患者依那普利拉水平也无显著差异。在停用ACEI治疗10至12周后，血细胞比容和血红蛋白分别从37.5±6.4显著升至39.7±3.6%（均值±标准差，P = 0.02）和从12.8±2.2升至13.5±1.2 g/dl，P = 0.04。同时，网织红细胞数量和促红细胞生成素浓度在2周、4周和10周后显著升高，在2周时达到峰值（分别从14.1±3.8升至20.6±8.0/1000，P < 0.05和从14.3±12.4升至29.3±54.5 mU/ml，P < 0.05）。总之，肾移植受者中与ACEI相关的贫血似乎是由于这类药物降低促红细胞生成素的作用。AZA与依那普利之间不太可能存在药代动力学相互作用，因为血浆依那普利拉水平与免疫抑制方案无关，且无论有无ACEI，AZA代谢产物水平均无变化。文中讨论了血管紧张素转换酶阻断可能导致循环促红细胞生成素减少的几种机制。
