Effects of Aliskiren on blood pressure and the predictive biomarkers for cardiovascular disease in hemodialysis-dependent chronic kidney disease patients with hypertension

摘要

The renin-angiotensin-aldosterone system (RAAS) has pivotal roles in the pathogenesis of hypertension in hemodialysis-dependent chronic kidney disease (HDD-CKD) patients. Activated RAAS also increases inflammatory mediators by directly increasing proinflammatory gene expression and by putting oxidative stress on the vascular endothelium. Both hypertension and inflammation are major risk factors for cardiovascular disease (CVD) in HDD-CKD patients. In this study, we assessed the efficacy of a direct renin inhibitor, aliskiren, on blood pressure (BP) and CVD predictive biomarkers, such as brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hs-CRP) and diacron-reactive oxygen metabolite (d-ROM). A total of 30 hypertensive HDD-CKD patients were assigned to receive aliskiren (150 mg) orally once daily with their existing antihypertensives. After 8 weeks, aliskiren treatments reduced systolic blood pressure (SBP) from 169.0 +-20.1 to 153.7 +- 19.6 mm Hg (P<0.001) and diastolic blood pressure (DBP) from 78.1 +- 12.0 to 73.0+- 13.6 mm Hg (P=0.048). RAAS was suppressed by aliskiren treatment as follows: PRA (from 3.6 +-4.0 to 1.0 +- 1.5 ng ml~(-1) (P=0.004)), angiotensin I (from 1704.0+-2580.9 to 233.7+- 181.0 pg ml~(-1) (P=0.009)), angiotensin II (from 70.2+- 121.5 to 12.4+- 11.5 ng ml~(-1) (P=0.022)) and aldosterone (from 107.9 +- 148.0 to 73.1 +-34.6 pg ml~(-1) (NS)), The biomarkers for CVD were inhibited by aliskiren: BNP (from 362.5 +-262.1 to 300.0 +- 232.0 pg ml~(-1) (P=0.043)), hS-CRP (from 6.2 +-8.1 to 3.5+-3.7 mg l~(-1) (P=0.022)) and d-ROM (from 367.0 +-89.8 to 328.3 +- 70.9 U.CARR (P=0.022)). The inhibition levels of biomarkers for CVD by aliskiren did not correlate with the decreased levels of SBP and DBP. These results suggested that aliskiren was effective for BP control and may have cardiovascular protective effects in hypertensive HDD-CKD patients.