Ménard Joël, Guyene Than-Tam, Peyrard Severine, Azizi Michel
Université Paris-Descartes, Faculté de Médecine, INSERM-AP-HP Clinical Investigation Center, Hôpital Européen Georges Pompidou, Paris, France.
J Hypertens. 2006 Mar;24(3):529-34. doi: 10.1097/01.hjh.0000209989.59230.2e.
Some renin inhibitors induce changes in the conformation of prorenin in vitro and influence the quantification of active renin by immunoradiometric assays. Whether such changes in renin recognition by monoclonal antibodies exist after oral administration of aliskiren, the first orally available renin inhibitor, is not known.
Two commercially available immunoradiometric assays (Cisbio and Nichols) were compared to determine immunoreactive active renin concentrations in plasma samples collected in a single oral dose crossover study comparing the renin inhibitor, aliskiren (300 mg), with the angiotensin II antagonist, valsartan (160 mg), in healthy male subjects.
The addition of aliskiren to plasma samples in vitro, at concentrations of 1-100 micromol/l, increased active renin immunoreactivity in both the Cisbio and Nichols assays. In the crossover study, the two assays gave similar values for the plasma immunoreactive active renin concentration before treatment and following valsartan administration (intraclass coefficient for agreement between the two assays = 0.92). However, a Bland-Altman plot showed a systematic bias towards higher values (1.75-fold higher; 95% confidence interval = 1.02-3.01) in the Nichols than in the Cisbio assay following aliskiren administration. The difference between the results obtained with the two assays depended on incubation time.
Depending on incubation conditions, circulating renin inhibitors interfere with the recognition of active renin molecules by the monoclonal antibodies used in commercially available assays. Careful consideration must therefore be given to the methodology used for quantifying immunoreactive plasma active renin when patients are treated with renin inhibitors, to avoid an overestimation of the magnitude of active renin release attributable to conformational changes in plasma prorenin.
一些肾素抑制剂在体外可诱导血管紧张素原构象发生变化，并影响免疫放射分析法定量活性肾素。目前尚不清楚口服首个可利用的肾素抑制剂阿利吉仑后，单克隆抗体对肾素的识别是否会发生此类变化。
在一项单剂量交叉研究中，比较了两种市售免疫放射分析法（Cisbio和Nichols），以测定健康男性受试者服用肾素抑制剂阿利吉仑（300 mg）和血管紧张素II拮抗剂缬沙坦（160 mg）后采集的血浆样本中免疫反应性活性肾素浓度。
在体外向血浆样本中添加浓度为1 - 100 μmol/l的阿利吉仑，可增加Cisbio和Nichols两种分析法中的活性肾素免疫反应性。在交叉研究中，两种分析法在治疗前和缬沙坦给药后的血浆免疫反应性活性肾素浓度值相似（两种分析法之间的组内一致性系数 = 0.92）。然而，Bland - Altman图显示，服用阿利吉仑后，Nichols分析法所得结果系统性偏高（高1.75倍；95%置信区间 = 1.02 - 3. of1），高于Cisbio分析法。两种分析法所得结果的差异取决于孵育时间。
根据孵育条件，循环肾素抑制剂会干扰市售分析法中所用单克隆抗体对活性肾素分子的识别。因此，当患者接受肾素抑制剂治疗时，必须仔细考虑用于定量免疫反应性血浆活性肾素的方法，以避免因血浆血管紧张素原构象变化导致活性肾素释放量被高估。
