Vakilzadeh Nima, Muller Marie-Eve, Forni Valentina, Milani Bastien, Hoffman Lucie, Piskunowicz Maciej, Maillard Marc, Zweiacker Carole, Pruijm Menno, Burnier Michel
Service of Nephrology and Hypertension, CHUV, University Hospital Lausanne, Switzerland.
Kidney Blood Press Res. 2015;40(5):542-54. doi: 10.1159/000368530. Epub 2015 Oct 26.
BACKGROUND/AIMS: The purpose of the present study was to compare the direct renin inhibitor aliskiren to the diuretic hydrochlorothiazide (HCTZ) in their ability to modulate renal tissue oxygenation in hypertensive patients.
24 patients were enrolled in this randomized prospective study and 20 completed the protocol. Patients were randomly assigned to receive either aliskiren 150-300 mg/d or HCTZ 12.5 - 25 mg/d for 8 weeks. Renal oxygenation was measured by BOLD-MRI at weeks 0 and 8. BOLD-MRI was also performed before and after an i.v. injection of 20 mg furosemide at week 0 and at week 8. BOLD-MRI data were analyzed by measuring the oxygenation in 12 computed layers of the kidney enabling to asses renal oxygenation according to the depth within the kidney and by the classical method of regions of interest (ROI).
The classical ROI analysis of the data showed no difference between the groups at week 8. The analysis of renal oxygenation according to the 12 layers method shows no significant difference between aliskiren and HCTZ at week 8 before administration of furosemide. However, within group analyses show that aliskiren slightly but not significantly increased oxygenation in the cortex and decreased medullary oxygenation whereas HCTZ induced a significant overall decrease in renal tissue oxygenation. With the same method of analysis we observed that the response to furosemide was unchanged in the HCTZ group at week 8 but was characterized by an increase in both cortical and medullary oxygenation in aliskiren-treated patients. Patients responding to aliskiren and HCTZ by a fall in systolic blood pressure of >10 mmHg improved their renal tissue oxygenation when compared to non-responders.
With the classical method of evaluation using regions no difference were found between aliskiren and HCTZ on renal tissue oxygenation after 8 weeks. In contrast, with our new method that takes into account the entire kidney, within group analyses show that aliskiren slightly increases cortical and medullary renal tissue oxygenation in hypertensive patients whereas HCTZ decreases significantly renal oxygenation at trough.
背景/目的：本研究旨在比较直接肾素抑制剂阿利吉仑与利尿剂氢氯噻嗪（HCTZ）对高血压患者肾组织氧合的调节能力。
24例患者纳入本随机前瞻性研究，20例完成研究方案。患者被随机分配接受阿利吉仑150 - 300mg/d或HCTZ 12.5 - 25mg/d，疗程8周。在第0周和第8周通过血氧水平依赖性功能磁共振成像（BOLD-MRI）测量肾氧合。在第0周和第8周静脉注射20mg呋塞米前后也进行BOLD-MRI检查。通过测量肾脏12个计算层面的氧合来分析BOLD-MRI数据，从而能够根据肾内深度评估肾氧合，并采用经典的感兴趣区域（ROI）方法。
数据的经典ROI分析显示第8周时两组之间无差异。根据12层面法对肾氧合的分析表明，在第8周给予呋塞米前，阿利吉仑和HCTZ之间无显著差异。然而，组内分析显示，阿利吉仑使皮质氧合略有增加但不显著，髓质氧合降低，而HCTZ导致肾组织氧合显著整体下降。采用相同的分析方法，我们观察到第8周时HCTZ组对呋塞米的反应未改变，但阿利吉仑治疗的患者皮质和髓质氧合均增加。收缩压下降>10mmHg的阿利吉仑和HCTZ反应者与无反应者相比，其肾组织氧合得到改善。
采用经典的感兴趣区域评估方法，8周后阿利吉仑和HCTZ在肾组织氧合方面无差异。相比之下，采用我们考虑整个肾脏的新方法，组内分析显示，阿利吉仑使高血压患者的皮质和髓质肾组织氧合略有增加，而HCTZ在谷值时显著降低肾氧合。
