Background: Patients suffering from chronic kidney disease (CKD)
have a higher risk of atrial fibrillation (AF) compared with the general
population, although the exact pathophysiological mechanisms underlying the
development of AF in CKD are incompletely understood. Furthermore, renal
denervation (RDN) resulting in decreased sympathetic activity has been
suggested to reduce both risk of spontaneous and inducible AF. Thus, this study
aims at characterizing the influence of CKD on development of AF and assessing whether
RDN may help to inhibit AF vulnerability in CKD.
Methods and Results: We compared left atrial (LA) fibrosis content by
Sirius red staining from 14 patients with AF and concomitant CKD
(GFR<60ml/min/1,73m2) to 16 AF-patients without CKD and 8 patients with
sinus rhythm. LA fibrosis formation was significantly increased in patients
with AF and CKD compared to AF without CKD or sinus rhythm. Furthermore, in a
translational approach, male Sprague-Dawley rats were fed for 16 weeks with
0.25% adenine (AD) diet to mimic slow development of CKD. After four weeks,
AD-treated rats were randomly subjected to either bilateral surgical renal
denervation (RDN; AD-RDN rats; n=15) or sham surgery (AD-rats; n=15). Rats on
normal chow served as control (Ctr; n=11). After 16 weeks, left atrial (LA)
dimension and function were assessed by echocardiography, inducibility of
arrhythmic episodes was tested by transesophageal burst-stimulation (20
burst-stimulations per animal), and in
vivo epicardial mapping of the LA was performed under anesthesia. Compared
with Ctr, both AD and AD-RDN rats exhibited higher plasma levels of creatinine
as well as higher plasma levels of urea. Echocardiography revealed pronounced diastolic
dysfunction as assessed by E/A ratio (Ctr: 1.10±0.02;
AD: 1.75±0.11, p<0.001 vs Ctr; AD-RDN: 1.19±0.07, p<0.001 vs AD) and increased left atrial diameters (Ctr: 4.22±0.05 mm; AD:
4.76±0.06 mm, p<0.0001 vs Ctr;
AD-RDN: 4.23±0.06 mm, p<0.0001 vs AD) in AD compared with
Ctr and AD-RDN rats. Analogously, induction of AF by transesophageal burst
stimulation was more likely in AD than in Ctr and AD-RDN rats. Moreover, in vivo epicardial mapping demonstrated impaired
LA conduction latency (Ctr: 1.4±0.1 s/m; AD: 2.3±0.2 s/m, p<0.01 vs Ctr) and increased absolute conduction
inhomogeneity (Ctr: 4.4±0.3 P5/P95; AD: 7.5±0.6
P5/P95, p<0.01 vs Ctr) in AD compared with Ctr. RDN-treatment decreased
AF-susceptibility and ameliorated LA conduction latency (AD-RDN: 1.5±0.2 s/m, p<0.01 vs AD) and absolute conduction inhomogeneity
(AD-RDN: 5.3±0.6 P5/P95, p<0.05 vs AD), independent of blood
pressure reduction and renal function.
Conclusion: In a rat model, induction of CKD leads to atrial structural
and electrophysiological remodeling. RDN resulting in decreased sympathetic
activity may preserve atrial function and reduce the risk of atrial
fibrillation in CKD independent of renal function and blood pressure reduction.