Instituto de Investigación Hospital 12 de Octubre, Department of Nephrology, Madrid, Spain.
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Centro de Investigación Biomédica en Red en Enfermedades Raras, Madrid, Spain.
Kidney Int. 2019 Oct;96(4):995-1004. doi: 10.1016/j.kint.2019.05.014. Epub 2019 May 31.
Malignant hypertension is listed among the causes of secondary thrombotic microangiopathy, but pathogenic mutations in complement genes have been reported in patients with hypertension-induced thrombotic microangiopathy. Here we investigated the frequency and severity of hypertension in 55 patients with primary atypical hemolytic uremic syndrome (aHUS). A genetic analysis was performed in all patients, and funduscopic examination was performed in all the patients with Grades 2 and 3 hypertension. A cohort of 110 patients with malignant hypertension caused by diseases other than aHUS served as control. Thirty-six patients with aHUS presented Grade 2 or Grade 3 hypertension and funduscopic examination showed malignant hypertension in 19. Genetic abnormalities in complement were found in 19 patients (37% among patients with malignant hypertension). Plasmapheresis was performed in 46 patients and 26 received eculizumab. Renal and hematological responses were significantly lower after plasmapheresis (24%) than after eculizumab (81%). Renal survival was significantly higher in patients treated with eculizumab (85% at one, three and five years) compared to patients who did not receive this treatment (54%, 46% and 41%), respectively. Response to eculizumab was independent of hypertension severity and the presence of complement genetic abnormalities. Among patients with malignant hypertension caused by other diseases the prevalence of thrombotic microangiopathy was very low (5%). Thus, severe and malignant hypertension are common among patients with aHUS and eculizumab treatment leads to a higher renal survival when compared to plasmapheresis. However, thrombotic microangiopathy is uncommon among patients presenting with malignant hypertension caused by diseases other than aHUS.
恶性高血压被列为继发性血栓性微血管病的原因之一,但在高血压引起的血栓性微血管病患者中已报道补体基因突变。在这里,我们调查了 55 例原发性非典型溶血尿毒综合征(aHUS)患者的高血压发生率和严重程度。对所有患者进行了基因分析,并对所有 2 级和 3 级高血压患者进行了眼底检查。一组 110 例由非 aHUS 疾病引起的恶性高血压患者作为对照组。36 例 aHUS 患者出现 2 级或 3 级高血压,眼底检查显示恶性高血压 19 例。在 19 例患者(恶性高血压患者中占 37%)中发现了补体异常。对 46 例患者进行了血浆置换,26 例患者接受了依库珠单抗治疗。血浆置换后的肾脏和血液学反应明显低于依库珠单抗(分别为 24%和 81%)。接受依库珠单抗治疗的患者的肾脏存活率明显高于未接受治疗的患者(分别为 85%、3 年和 5 年,54%、46%和 41%)。依库珠单抗的反应与高血压严重程度和补体基因突变的存在无关。在由其他疾病引起的恶性高血压患者中,血栓性微血管病的发生率非常低(5%)。因此,严重和恶性高血压在 aHUS 患者中很常见,与血浆置换相比,依库珠单抗治疗可提高肾脏存活率。然而,由非 aHUS 疾病引起的恶性高血压患者中,血栓性微血管病并不常见。