Increased heart rate is associated with intrarenal renin-angiotensin system activation in chronic kidney disease patients.

Abstract

A higher heart rate is one of the risk factors for heart failure and cardiovascular disease. Activation of the intrarenal renin-angiotensin system (RAS) plays an important role in the development of hypertension and renal damage. However, the association between heart rate and intrarenal RAS activation is unclear. We investigated the relationship between heart rate and urinary angiotensinogen (U-AGT) excretion, a surrogate marker for intrarenal RAS activity, in ten subjects without chronic kidney disease (CKD) and 72 CKD patients who were not taking medications that influence heart rate and RAS blockers (age 50.0 ± 17.4years, 27 men and 45 women, serum creatinine (sCr) 1.85 ± 2.71mg/dL, blood pressure 120.5 ± 15.8/72.9 ± 10.1mmHg, heart rate 67.3 ± 8.9 /min, urinary protein excretion 1.27 ± 2.63g/day, and U-AGT excretion 747.4 ± 2714.6µg/day). As heart rate is influenced by behavior and emotion, we divided it into daytime and nighttime. Heart rate had a significant positive association with sCr levels during daytime and nighttime in CKD patients but not in non-CKD subjects. Moreover, although heart rate was not associated with U-AGT excretion levels in non-CKD subjects, it was associated with U-AGT excretion levels during daytime (r = 0.23 and p = 0.047) and nighttime (r = 0.45 and p < 0.01) in CKD patients. Multiple linear regression analysis revealed that heart rate had a significant positive association with the U-AGT excretion levels during nighttime, but not daytime, after adjustments for age, sex, body mass index, and sCr (β = 0.31 and p = 0.034). Heart rate is associated with U-AGT excretion levels, especially during the nighttime, in CKD patients.