PS-BPB01-8: IMPACT OF DIFFERENT DIURETIC TYPES ON ARTERIAL STIFFNESS AND CALCIFICATION IN A RAT MODEL OF CHRONIC KIDNEY DISEASE

Abstract

Introduction: We reported that antihypertensive therapy with a hydrochlorothiazide (HCTZ)-based regimen aggravates arterial stiffness and vascular calcification in a rat model of chronic kidney disease (CKD) with mineral and bone disorder (MBD). In this study, we investigated whether the aggravation of arterial stiffness and vascular calcification in CKD-MBD rats is induced by HCTZ and whether these abnormalities could also occur with other types of diuretic currently used in clinic. Methods: In rats with renal mass ablation-induced CKD, MBD was generated by a Ca/P-rich diet and calcitriol supplementation. The animals were divided into 4 groups; 1) CKD-MBD control; 2) CKD-MBD + HCTZ (thiazide diuretic, 5 mg/kg/d); 3) CKD-MBD + Chlorthalidone (thiazide-like diuretic, 5 mg/kg/d), and; 4) CKD-MBD + Furosemide (loop diuretics, 10 mg/kg/d). At week 6, hemodynamic parameters including systolic and mean blood pressure (SBP and MBP), pulse pressure (PP) and pulse wave velocity (PWV) were determined. The thoracic aorta was harvested to assess vascular calcification. Results: SBP was reduced by all types of diuretic in CKD-MBD rats. Contrary to chlortalidone nor furosemide, HCTZ treatment led to a reduction of MBP, but an increase in PP and PWV in CKD-MBD rats (p < 0.05). As expected from these hemodynamic changes, medial calcification in the thoracic aorta was significantly greater in CKD-MBD rats treated with HCTZ as compared to all the other groups of rats (p < 0.05). Conclusion: In rats with CKD-MBD, antihypertensive therapy with the thiazide diuretic HCTZ, but not other types of diuretic, exacerbated arterial stiffness and vascular calcification despite a reduction in SBP. The deleterious effect of HCTZ in CKD-MBD rats may have major clinical impact as this diuretic is widely use in patients with CKD that often develop MBD.