The impact of antihypertensive drug therapy on endotoxemia in elderly patients with chronic kidney disease.

Abstract

BACKGROUND AND OBJECTIVES: Endotoxin (ET) is recognized to cause adverse effects on cardiovascular (CV) structure. Circulatory translocation of gut bacterial ET is described in heart failure. Chronic kidney disease (CKD) is common in older people and aggressive BP control is the cornerstone of management. We therefore studied ET after improvement of the overall CV milieu with introduction of optimized antihypertensive therapy (AHT). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We recruited 40 hypertensive nondiabetic patients (≥70 years) with CKD stages 3 and 4 and hypertensive non-CKD matched controls. Assessment was performed after complete AHT washout and repeated after AHT reintroduction to target BP 130/80 mmHg. Pulse wave velocity (PWV) and analysis were assessed by applanation tonometry, central hemodynamics by continuous digital pulse wave analysis, vascular calcification (VC) by superficial femoral artery CT, and serum ET by Limulus Amebocyte assay. RESULTS: Mean age was 76 ± 5 years, estimated GFR (eGFR) (CKD group) was 40 ± 14 ml/min per 1.73 m(2), and achieved BP was 128/69 mmHg. Washout ET was 0.042 ± 0.011 EU/ml and was independent of renal function, gender, age, BP, VC, arterial stiffness, and high-sensitivity C-reactive protein. ET significantly decreased with AHT (to 0.020 ± 0.028 EU/ml; P < 0.001) and was associated with eGFR (R = -0.38; P = 0.02), arterial wave reflection (Augmentation Index R = -0.42; P = 0.01), and degree of tonic vasodilatation (total peripheral resistance R = -0.37; P = 0.03), but not VC, PWV, gender, age, BP, or high-sensitivity C-reactive protein. CONCLUSIONS: Elderly patients with hypertension have elevated serum ET. Improvement of their CV status with optimized AHT is associated with a significant reduction in endotoxemia. Further investigation of the potential pathophysiological mechanisms linking CV disease and CKD with this previously unappreciated effect of AHT appears warranted.