Cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) is high, and the presence of CKD worsens outcomes of cardiovascular disease (CVD). CKD is associated with specific risk factors. Emerging evidence indicates that the pathology and manifestation of CVD differ in the presence of CKD. During a clinical update conference convened by the Kidney Disease: Improving Global Outcomes (KDIGO), an international group of experts defined the current state of knowledge and the implications for patient care in important topic areas, including coronary artery disease and myocardial infarction, congestive heart failure, cerebrovascular disease, atrial fibrillation, peripheral arterial disease, and sudden cardiac death. Although optimal strategies for prevention, diagnosis, and management of these complications likely should be modified in the presence of CKD, the evidence base for decision making is limited. Trials targeting CVD in patients with CKD have a large potential to improve outcomes.

Sudden cardiac arrest is the most common cause of death among patients with end-stage kidney disease (ESKD) maintained on hemodialysis. Here we sought to identify dialysis-related factors associated with this increased risk in a case-control study encompassing 43,200 patients dialyzed in outpatient clinics of a large organization. Within this group, we compared the clinical and dialysis-specific data of 502 patients who experienced a sudden cardiac arrest with 1632 age- and dialysis-vintage-matched controls. There were 4.5 sudden cardiac arrest events per 100,000 dialysis treatments during the 3-year study period. These patients were significantly more likely to have been exposed to low potassium dialysate of less than 2 meq/l. These differences could not be explained by predialysis serum potassium levels. There was no evidence for a beneficial effect of low potassium dialysate even among those with higher predialysis serum potassium levels. Other factors strongly associated with sudden cardiac arrest by multivariable analysis included increased ultrafiltration volumes, exposure to low calcium dialysate, and predialysis serum creatinine levels. These relationships persisted after adjustment for covariates, but traditional risk factors such as history of coronary heart disease and congestive heart failure were not significantly influential. Hence, our study suggests that modifications of the hemodialysis prescription may improve the risk of sudden cardiac arrest in patients with ESKD.

Sudden cardiac death is the most common cause of mortality among patients with end stage kidney disease maintained on hemodialysis. To examine whether this increased risk is also seen with less advanced kidney disease we studied the relationship between glomerular filtration rate and risk of sudden cardiac death in patients with moderate kidney disease and known coronary artery disease. This retrospective longitudinal study encompassed 19,440 consecutive patients who underwent cardiac catheterization at a single academic institution. There were 522 adjudicated sudden cardiac death events yielding an overall rate of 4.6 events per 1000 patient years. This figure reflected rates of 3.8 events in 14,652 patients with estimated glomerular filtration rates (eGFR) ≥60 (stage 2 CKD or better) and 7.9 events in 4788 patients with glomerular filtration rates <60 (stage 3–5 CKD), all normalized to 1000 patient years. After adjusting for differences in known cardiac risk factors and other covariates in a multivariate Cox proportional hazards model, the eGFR was independently associated with sudden cardiac death (HR 1.11 per 10 ml/min decline in the eGFR). Our analysis found that reductions in the eGFR in CKD stages 3–5 are associated with a progressive increase in risk of sudden cardiac death in patients with coronary artery disease. Additional studies are needed to better characterize the mechanisms by which reduced kidney function increases this risk.

Hemodialysis patients carry a large burden of cardiovascular disease; most onerous is the high risk of sudden cardiac death. Defining sudden cardiac death among hemodialysis patients as well as understanding its pathogenesis is challenging, but inferences from existing literature reveal differences between sudden cardiac death among hemodialysis patients and the general population. Vascular calcifications and left ventricular hypertrophy may play a role in the pathophysiology of sudden cardiac death whereas traditional cardiovascular risk factors seem to have a more muted effect. Arrhythmic triggers also differ in this group as compared to the general population, with some arising uniquely from the hemodialysis procedure. Combined, these factors may alter the types of terminal arrhythmias that lead to sudden cardiac death among hemodialysis patients, having important implications for prevention strategies. This review highlights current knowledge on the epidemiology, pathophysiology, and risk factors for sudden cardiac death among hemodialysis patients. We then examine strategies for prevention including use of specific cardiac medications and device-based therapies such as implantable defibrillators. We also discuss dialysis-specific prevention strategies including minimizing exposure to low potassium and calcium dialysate, extending dialysis treatment times or adding sessions to avoid rapid ultrafiltration, and lowering dialysate temperature.

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One of the fundamental goals of the hemodialysis prescription is to maintain serum potassium levels within a narrow normal range during both the intradialytic and interdialytic intervals. Considering the extraordinarily high rate of cardiovascular mortality in the hemodialysis population, clinicians are obligated to explore whether factors related to dialytic potassium removal can be modified to improve clinical outcomes. Observational studies and circumstantial evidence suggest that extreme concentrations of serum and dialysate potassium can trigger cardiac arrest. In this review, we provide an overview of factors affecting overall potassium balance and factors modulating potassium dialysate fluxes in dialysis, and we review data linking serum and dialysate potassium concentrations with arrhythmias, cardiovascular events, and mortality. We explore potential interactions between serum and dialysate magnesium levels and risks associated with dialysate potassium levels. Finally, we conclude with proposed dialytic and novel nondialytic approaches to optimize outcomes related to potassium homeostasis in patients on hemodialysis. Dialysis clinicians need to consider changes in the overall clinical scenario when choosing dialysate potassium concentrations, and an effective change in practice will require more frequent serum potassium monitoring and responsive dialysis care teams.

SummaryBackground and objectives The optimal dialysate calcium concentration to maintain normal mineralization and reduce risk of cardiovascular events in hemodialysis patients is debated. Guidelines suggest that dialysate Ca concentration should be lowered to avoid vascular calcification, but cardiac arrhythmias may be more likely to occur at lower dialysate Ca. Concurrent use of QT-prolonging medications may also exacerbate arrhythmic risk. This study examined the influence of serum Ca, dialysate Ca, and QT interval-prolonging medications on the risk of sudden cardiac arrest in a cohort of hemodialysis patients.Design, setting, participants, & measurements This case-control study among 43,200 hemodialysis patients occurred between 2002 and 2005; 510 patients who experienced a witnessed sudden cardiac arrest were compared with 1560 matched controls. This study examined covariate-adjusted sudden cardiac arrest risk associations with serum Ca, dialysate Ca, serum dialysate Ca gradient, and prescription of QT-prolonging medications using logistic regression techniques.Results Patients assigned to low Ca dialysate,2.5 mEq/L were more likely to be exposed to larger serum dialysate Ca gradient and had a greater fall in BP during dialysis treatment. After accounting for covariates and baseline differences, low Ca dialysate,2.5 mEq/L (odds ratio=2.00, 95% confidence interval=1.40-2.90), higher corrected serum Ca (odds ratio=1.10, 95% confidence interval=1.00-1.30), and increasing serum dialysate Ca gradient (odds ratio=1.40, 95% confidence interval=1.10-1.80) were associated with increased risk of sudden cardiac arrest, whereas there were no significant risk associations with QT-prolonging medications.Conclusions Increased risk of sudden cardiac arrest associated with low Ca dialysate and large serum dialysate Ca gradients should be considered in determining the optimal dialysate Ca prescription.

Background-The benefit of a primary prevention implantable cardioverter defibrillator (ICD) among patients with chronic kidney disease (CKD) is uncertain.