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Among patients with end-stage renal disease (ESRD) treated with renal replacement therapy, cardiovascular disease is a leading cause of morbidity and mortality. Although the incidence and outcomes of congestive heart failure, strokes, myocardial infarction and other atherosclerotic complications among dialysis patients have been well characterized, scant attention has been paid to cardiac conduction system diseases. Sudden death is the direst manifestation of such a disease and is now eminently treatable with the use of permanent pacemakers (PPMs) and automatic intracardiac defibrillator devices [1]. Nonetheless, few studies have evaluated the magnitude of this problem. In this issue of Nephrology Dialysis Transplantation, Wang et al. [2] report the incidence of cardiac conduction system disorders that are severe enough to lead to implantation of a PPM utilizing the large Taiwan National Health Insurance Database. Between 2000 and 2010, the investigators identified over 28 000 newly diagnosed ESRD patients [9700 on peritoneal dialysis (PD) and 18 771 on hemodialysis (HD)] and 113 769 controls randomly selected without clinical kidney disease to evaluate the incidence of PPM implantation through 31 December 2011. Control subjects were matched to the ESRD group by age sex and index year. There were 143 PPM implantations in the control group (n = 113 769) and 139 in the ESRD group (n = 28 471). The incidence rate of PPM implantation per 1000 patient years was 0.25 in controls and 1.27 among those with ESRD. The incidence rate of PPM implantation was 0.88 in PD patients and 1.46 in HD patients. Compared with the control group, the crude hazard ratio adjusted for age and sex was 5.1 for ESRD. The crude hazard ratio among PD patients was 3.5 and among HD patients 5.8. The higher incidence rate among HD patients was not surprising given that HD patients had a greater age, and higher incidences of coronary artery disease, diabetes mellitus, stroke, dyslipidemia and congestive heart failure, and they also used more antiplatelet agents. Adjusting for the baseline differences revealed that the adjusted hazard ratio among PD patients was 2.4 compared with 3.2 among HD patients. In propensity-matched analyses, the two adjusted hazard ratios were not statistically different. Accordingly, compared with PD, HD per sewas not associated with increased risk of pacemaker implantation. Compared with the control group, the crude hazard ratio of pacemaker implantation was 5.1 in ESRD. Adjusted for various comorbidities such as diabetes, previous coronary artery disease, stroke, etc., the hazard ratio fell to 2.9 [95% confidence interval (CI) 2.22–3.89]. Thus, it appears that ESRD is strongly associated with conduction system disease and not simply related to conditions such as the presence of diabetes or coronary artery disease. ESRD is plausibly related to accelerated conduction system disease for several reasons [3]. It has now long been recognized that chronic kidney disease is associated with cardiomyocyte capillary mismatch [4]. Ischemia to the conduction system is therefore a real possibility in ESRD. Enhanced myocardial fibrosis may promote the substrate for arrhythmogenesis in this vulnerable population. Like the propensity for vascular calcification, it is possible that the cardiac conduction system is also vulnerable to calcify [5]. This may further worsen the cardiac conduction system disease. Volume overload and therefore cardiac chamber dilatation are common in this population and may predispose to arrhythmias. ESRD is a state of enhanced sympathetic activation, which may further promote arrhythmias [6]. An interesting observation made in this cohort is that the tempo of disease among the PD and HD patients was quite different. The incidence rate of PPM implantation (per 1000 patient-years) was 0.54 in the PD group and 1.99 HD group in the first year of follow-up. In an analysis that was propensity score matched, the adjusted hazard ratio was 3.81 (95% CI 1.41–10.3). When the follow-up time was 1–3 years, the incidence rate in the PD group was 0.68 versus 1.32 in the HD group. When the follow-up time was >3 years, the incidence rate of PPM implantation was 1.30 in the PD group and 1.28 in the HD. Thus, it appears that there is an accelerated rate of conduction system disease among HD patients. However, if ESRD patients lived >3 years, PD patients ultimately had the same degree of conduction system disease as those on HD. IN F O C U S

The natural history of symptomatic cardiac conduction-system disease in end-stage renal disease