Abstract
BackgroundChronic kidney disease and occurrence of atrial fibrillation (AF) are closely related. No studies have examined whether renal impairment (RI) without severe renal dysfunction is associated with the occurrence of AF.MethodsUnilateral RI with mild renal insufficiency was induced in beagles by embolization of small branches of the renal artery in the left kidney for 2 weeks using gelatin sponge granules in the model group (n = 5). The sham group (n = 5) underwent the same procedure, except for embolization. Parameters associated with RI and renal function were tested, cardiac electrophysiological parameters, blood pressure, left ventricular pressure, and AF vulnerability were investigated. The activity of the sympathetic nervous system, renin-angiotensin-aldosterone system, inflammation, and oxidative stress were measured. Histological studies associated with atrial interstitial fibrosis were performed.ResultsEmbolization of small branches of the renal artery in the left kidney led to ischemic RI with mild renal insufficiency. The following changes occurred after embolization. Heart rate and P wave duration were increased. Blood pressure and left ventricular systolic pressure were elevated. The atrial effective refractory period and antegrade Wenckebach point were shortened. Episodes and duration of AF, as well as atrial and ventricular rate during AF were increased in the model group. Plasma levels of norepinephrine, renin, and aldosterone were increased, angiotensin II and aldosterone levels in atrial tissue were elevated, and atrial interstitial fibrosis was enhanced after 2 weeks of embolization in the model group.ConclusionsWe successfully established a model of RI with mild renal insufficiency in a large animal. We found that RI with mild renal insufficiency was associated with AF in this model.
Highlights
The prevalence of atrial fibrillation (AF) in the general population is 1% [1] A recent meta-analysis showed that the prevalence of AF in end-stage renal disease patients was 11.6% [2]
After 2 weeks of operation, Creatinine clearance (CCr) in the model group was slightly decreased by 27.5% (P,0.05) compared with the sham group
The main findings of our study were: 1) embolization of small renal artery branches of the left kidney for 2 weeks resulted in ischemic renal impairment (RI) with mild renal insufficiency; 2) RI with mild renal insufficiency was associated with vulnerability to AF; 3) increased vulnerability of AF might be associated with increased activity of the sympathetic nervous system (SNS), renin-angiotensin-aldosterone system (RAAS), and atrial fibrosis in the model of RI with mild renal insufficiency
Summary
The prevalence of atrial fibrillation (AF) in the general population is 1% [1] A recent meta-analysis showed that the prevalence of AF in end-stage renal disease patients was 11.6% [2]. The Chronic Renal Insufficiency Cohort study suggested that the prevalence of AF is 2–3-fold higher in patients with mild-tomoderate chronic kidney disease (CKD) than in the general population [3]. Renal dysfunction is associated with an increased risk of stroke and mortality in patients with AF [5]. Exploring the inherent pathogenic mechanisms responsible for the development of AF among CKD patients and identifying effective therapeutic targets are urgent. Chronic kidney disease and occurrence of atrial fibrillation (AF) are closely related. No studies have examined whether renal impairment (RI) without severe renal dysfunction is associated with the occurrence of AF
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