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Background Hypokalemia is a risk factor for drug-induced QT prolongation. Larger serum-to-dialysate potassium gradients during hemodialysis (HD) may augment the proarrhythmic risks of selective serotonin reuptake inhibitors (SSRIs). Methods We conducted a cohort study using 2007–2017 data from the United States Renal Data System and a large dialysis provider to examine if the serum-to-dialysate potassium gradient modifies SSRI cardiac safety. Using a new-user design, we compared 1-year sudden cardiac death (SCD) risk among HD patients newly treated with higher (citalopram, escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, sertraline) QT-prolonging potential SSRIs, overall and stratified by baseline potassium gradient (≥4 versus <4 mEq/l). We used inverse probability of treatment-weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) and conducted a confirmatory nested case–control study. Results The study included 25   099 patients: 11   107 (44.3%) higher QT-prolonging potential SSRI new users and 13   992 (55.7%) lower QT-prolonging potential SSRI new users. Overall, higher versus lower QT-prolonging potential SSRI use was not associated with SCD [weighted HR 1.03 (95% CI 0.86–1.24)]. However, a greater risk of SCD was associated with higher versus lower QT-prolonging potential SSRI use among patients with baseline potassium gradients ≥4 mEq/l but not among those with gradients <4 mEq/l [weighted HR 2.17 (95% CI 1.16–4.03) versus 0.95 (0.78–1.16)]. Nested case–control analyses yielded analogous results. Conclusions The serum-to-dialysate potassium gradient may modify the association between higher versus lower QT-prolonging SSRI use and SCD among people receiving HD. Minimizing the potassium gradient in the setting of QT-prolonging medication use may be warranted. [ABSTRACT FROM AUTHOR]

Purpose: Polypharmacy is common in the hemodialysis population and increases the likelihood that patients will be exposed to clinically significant drug–drug interactions. Concurrent use of proton pump inhibitors (PPIs) with citalopram or escitalopram may potentiate the QT‐prolonging effects of these selective serotonin reuptake inhibitors through pharmacodynamic and/or pharmacokinetic interactions. Methods: We conducted a retrospective cohort study using data from the U.S. Renal Data System (2007–2017) and a new‐user design to examine the differential risk of sudden cardiac death (SCD) associated with citalopram/escitalopram initiation vs. sertraline initiation in the presence and absence of PPI use among adults receiving hemodialysis. We studied 72 559 patients:14 983 (21%) citalopram/escitalopram initiators using a PPI; 26 503 (36%) citalopram/escitalopram initiators not using a PPI;10 779 (15%) sertraline initiators using a PPI; and 20 294 (28%) sertraline initiators not using a PPI (referent). The outcome of interest was 1‐year SCD. We used inverse probability of treatment weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Compared with sertraline initiators not using a PPI, citalopram/escitalopram initiators using a PPI had the numerically highest risk of SCD (HR [95% CI] = 1.31 [1.11–1.54]), followed by citalopram/escitalopram initiators not using a PPI (HR [95% CI] = 1.22 [1.06–1.41]). Sertraline initiators using a PPI had a similar risk of SCD compared with those not using a PPI (HR [95% CI] = 1.03 [0.85–1.26]). Conclusions: Existing PPI use may elevate the risk of SCD associated with citalopram or escitalopram initiation among hemodialysis patients. [ABSTRACT FROM AUTHOR]

Nephrologists are faced with a difficult dilemma in choosing the ideal dialysis prescription to maintain neutral potassium mass balance. Should potassium mass balance goals prioritize the normalization of serum potassium levels using low potassium dialysate at the expense of provoking intradialytic arrhythmias, or should mass balance goals favor permissive hyperkalemia using higher dialysate potassium to avoid rapid intradialytic fluxes at the risk of more interdialytic arrhythmias? This review examines the factors that determine potassium mass balance among HD patients, the relationships between serum and dialysate potassium levels and outcomes, and concludes by examining currently available approaches to reducing risk of arrhythmias while managing potassium mass balance. [ABSTRACT FROM AUTHOR]

Among patients receiving hemodialysis, abnormalities in calcium regulation have been linked to an increased risk of cardiovascular events. Cinacalcet lowers serum calcium concentrations through its effect on parathyroid hormone secretion and has been hypothesized to reduce the risk of cardiovascular events. In observational cohort studies, prescriptions of low dialysate calcium concentration and larger observed serum-dialysate calcium gradients have been associated with higher risks of in-dialysis facility or peri-dialytic sudden cardiac arrest. We performed this study to examine the risks associated with dialysate calcium and serum-dialysate gradients among participants in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events ( EVOLVE) trial. In EVOLVE, 3883 hemodialysis patients were randomized 1:1 to cinacalcet or placebo. Dialysate calcium was administered at the discretion of treating physicians. We examined whether baseline dialysate calcium concentration or the serum-dialysate calcium gradient modified the effect of cinacalcet on the following adjudicated endpoints: (1) primary composite endpoint (death or first non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular event); (2) cardiovascular death; and (3) sudden death. In EVOLVE, use of higher dialysate calcium concentrations was more prevalent in Europe and Latin America compared with North America. There was a significant fall in serum calcium concentration in the cinacalcet group; dialysate calcium concentrations were changed infrequently in both groups. There was no association between baseline dialysate calcium concentration or serum-dialysate calcium gradient and the endpoints examined. Neither the baseline dialysate calcium nor the serum-dialysate calcium gradient significantly modified the effects of cinacalcet on the outcomes examined. The effects of cinacalcet on cardiovascular death and major cardiovascular events are not altered by the dialysate calcium prescription and serum-dialysate calcium gradient. [ABSTRACT FROM AUTHOR]

Background: Guidelines recommend that implantable cardioverter-defibrillator (ICD) candidates have an estimated longevity of ≥1 year. Longevity can be affected by chronic kidney disease (CKD).Methods and Results: Using the National Cardiovascular Data Registry ICD registry linked with the Social Security Death Master File, we assessed the rate of death after primary prevention ICD placement between January 1, 2006, and December 31, 2007, according to CKD stage. Using Cox models, we identified factors associated with death among patients with CKD. Compared with patients without CKD (n=26,056), those with CKD (n=21,226) were older, less commonly men, more often white, and more frequently had comorbid illness. Compared with patients without CKD, patients with a glomerular filtration rate 30 to 60, glomerular filtration rate <30, and end-stage renal disease on dialysis had a higher risk of death after ICD placement (hazard ratio, 2.08; 95% confidence interval, 1.99-2.18; P<0.0001; hazard ratio, 4.20; 95% confidence interval, 3.92-4.50; P<0.0001; and hazard ratio, 4.80; 95% confidence interval, 4.46-5.17; P<0.0001, respectively). Corresponding 1-year death rates were 4.4%, 9.1%, 20.2%, and 22.4%. Among patients with CKD, factors associated with increased risk of death included CKD severity, age >65 years, heart failure symptoms, diabetes mellitus, lung disease, serum sodium <140 mEq/L, atrial fibrillation or flutter, and a lower ejection fraction.Conclusions: The risk of death after primary prevention ICD placement is proportional to CKD severity. Among patients with CKD, several factors are prognostically significant and could inform clinical decision making on primary prevention ICD candidacy. [ABSTRACT FROM AUTHOR]

Sudden cardiac death is a major problem in hemodialysis patients, and our understanding of this disease is underdeveloped. The lack of a precise definition tailored for use in the hemodialysis population limits the reliability of epidemiologic reports. Efforts should be directed toward an accurate classification of all deaths that occur in this vulnerable population. The traditional paradigm of disease pathophysiology based on known cardiac risk factors appears to be inadequate to explain the magnitude of sudden cardiac death risk in chronic kidney disease, and numerous unique cofactors and exposures appear to determine risk in this population. Well-designed cohort studies will be needed for a basic understanding of disease pathophysiology and risk factors, and randomized intervention trials will be needed before best management practices can be implemented. This review examines available data to describe the characteristics of the high-risk patient and suggests a comprehensive common sense approach to prevention using existing cardiovascular medications and reducing and monitoring potential dialysis-related arrhythmic triggers. Other unproven cardiovascular therapies such as implantable cardioverter defibrillators should be used on a case-by-case basis, with recognition of the associated hazards that these devices carry among hemodialysis patients. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (hazard ratio (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. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) have an inordinate risk of cardiovascular disease. In addition to the metabolic state of uremia, the CKD-associated risk is partly explainable by unique cofactors such as dyslipidemia, systemic inflammation, and exposures that occur during renal replacement therapies. However, the comorbid condition of hypertension also enhances risk in patients with CKD. New observations suggest that diminished glomerular filtration rate and hypertension share primacy in the development of cardiovascular illness. [ABSTRACT FROM AUTHOR]

A response by Patrick H. Pun and his colleagues to a letter to the editor about their article "Chronic kidney disease is associated with increased risk of sudden cardiac death among patients with coronary artery disease," published in the 2009 issue of the periodical is presented.

A response by Patrick H. Pun and colleagues to a letter to the editor regarding their article "Modifiable risk factors associated with sudden cardiac arrest within hemodialysis clinics" in the 2010 issue is presented.

Background: Cardiac arrest is the leading cause of death among patients receiving hemodialysis. Despite guidelines recommending CPR training and AED presence in dialysis clinics, rates of CPR and AED use by dialysis staff are suboptimal. Given that racial disparities exist in bystander CPR administration in non-healthcare settings, we examined the relationship between patient race/ethnicity and staff-initiated CPR and AED application within dialysis clinics.Methods: We analyzed data prospectively collected in the Cardiac Arrest Registry to Enhance Survival across the U.S. from 2013 to 2017 and the Centers for Medicare & Medicaid Services dialysis facility database to identify outpatient dialysis clinic cardiac arrest events. Using multivariable logistic regression models, we examined relationships between patient race/ethnicity and dialysis staff-initiated CPR and AED application.Results: We identified 1568 cardiac arrests occurring in 809 hemodialysis clinics. The racial/ethnic composition of patients was 31.3% white, 32.9% Black, 10.7% Hispanic/Latinx, 2.7% Asian, and 22.5% other/unknown. Overall, 88.0% of patients received CPR initiated by dialysis staff, but rates differed by race: 91% of white patients, 85% of black patients, and 77% of Asian patients (p = 0.005). After adjusting for differences in patient and clinic characteristics, black (OR = 0.41, 95% CI 0.25-0.68) and Asian patients (OR = 0.28, 95% CI 0.12-0.65) were significantly less likely than white patients to receive staff-initiated CPR. No significant difference between staff-initiated CPR rates among white, Hispanic/Latinx, and other/unknown patients was observed. An AED was applied by dialysis staff in 62% of patients. In adjusted models, there was no relationship between patient race/ethnicity and staff AED application.Conclusions: Black and Asian patients are significantly less likely than white patients to receive CPR from dialysis staff. Further understanding of practices in dialysis clinics and increased awareness of this disparity are necessary to improve resuscitation practices. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rationale & Objective: Black patients and those with diabetes or reduced kidney function experience a disproportionate burden of acute kidney injury (AKI) and cardiovascular events. However, whether these factors modify the association between AKI and cardiovascular events after percutaneous coronary intervention (PCI) is unknown and was the focus of this study., Study Design: Observational cohort., Setting & Participants: Patients who underwent PCI at Duke between January 1, 2003, and December 31, 2013, with data available in the Duke Databank for Cardiovascular Disease., Exposure: AKI, defined as ≥1.5-fold relative elevation in serum creatinine within 7 days from a reference value ascertained 30 days before PCI, or a 0.3 mg/dL increase from the reference value within 48 hours., Outcome: A composite of all-cause death, myocardial infarction, stroke, or revascularization during the first year after PCI., Analytical Approach: Cox regression models adjusted for potential confounders and with interaction terms between AKI and race, diabetes, or baseline estimated glomerular filtration rate (eGFR)., Results: Among 9,422 patients, 9% (n = 865) developed AKI, and the primary composite outcome occurred in 21% (n = 2,017). AKI was associated with a nearly 2-fold higher risk of the primary outcome (adjusted HR, 1.94 [95% CI, 1.71-2.20]). The association between AKI and cardiovascular risk did not significantly differ by race (P interaction, 0.4), diabetes, (P interaction, 0.06), or eGFR (P interaction, 0.2). However, Black race and severely reduced eGFR, but not diabetes, each had a cumulative impact with AKI on risk for the primary outcome. Compared with White patients with no AKI as the reference, the risk for the outcome was highest in Black patients with AKI (HR, 2.27 [95% CI, 1.83-2.82]), followed by White patients with AKI (HR, 1.87 [95% CI, 1.58-2.21]), and was least in patients of other races with AKI (HR, 1.48 [95% CI, 0.88-2.48])., Limitations: Residual confounding, including the impact of clinical care following PCI on cardiovascular outcomes of AKI., Conclusions: Neither race, diabetes, nor reduced eGFR potentiated the association of AKI with cardiovascular risk, but Black patients with AKI had a qualitatively greater risk than White patients with AKI or patients of other races with AKI., Plain-Language Summary: This study examined differences by race, diabetes, or kidney function in the well-known association of AKI with increased risk for cardiovascular outcomes among patients undergoing percutaneous coronary intervention. The authors found that AKI was associated with a greater risk for cardiovascular outcomes, but this risk did not differ by patients' race, diabetes status, or level of kidney function before the procedure. That said, the risk for cardiovascular outcomes was numerically highest among Black patients compared with White patients or those of other races. These study findings suggest that future efforts to prevent AKI among patients undergoing the procedure could reduce racial disparities in risk for unfavorable cardiovascular outcomes afterward., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Hypokalemia is a risk factor for drug-induced QT prolongation. Larger serum-to-dialysate potassium gradients during hemodialysis (HD) may augment the proarrhythmic risks of selective serotonin reuptake inhibitors (SSRIs)., Methods: We conducted a cohort study using 2007-2017 data from the United States Renal Data System and a large dialysis provider to examine if the serum-to-dialysate potassium gradient modifies SSRI cardiac safety. Using a new-user design, we compared 1-year sudden cardiac death (SCD) risk among HD patients newly treated with higher (citalopram, escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, sertraline) QT-prolonging potential SSRIs, overall and stratified by baseline potassium gradient (≥4 versus &lt;4 mEq/l). We used inverse probability of treatment-weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) and conducted a confirmatory nested case-control study., Results: The study included 25 099 patients: 11 107 (44.3%) higher QT-prolonging potential SSRI new users and 13 992 (55.7%) lower QT-prolonging potential SSRI new users. Overall, higher versus lower QT-prolonging potential SSRI use was not associated with SCD [weighted HR 1.03 (95% CI 0.86-1.24)]. However, a greater risk of SCD was associated with higher versus lower QT-prolonging potential SSRI use among patients with baseline potassium gradients ≥4 mEq/l but not among those with gradients &lt;4 mEq/l [weighted HR 2.17 (95% CI 1.16-4.03) versus 0.95 (0.78-1.16)]. Nested case-control analyses yielded analogous results., Conclusions: The serum-to-dialysate potassium gradient may modify the association between higher versus lower QT-prolonging SSRI use and SCD among people receiving HD. Minimizing the potassium gradient in the setting of QT-prolonging medication use may be warranted., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Cardiac arrest occurs frequently in outpatient dialysis clinics, and immediate cardiopulmonary resuscitation (CPR) provision improves patient outcomes. However, Black patients in dialysis clinics receive CPR from clinic staff less often compared with White patients. We examined the role of dialysis facility resources and patient factors in the observed racial disparity in CPR receipt and automated external defibrillator application., Methods: This was a retrospective cohort study linking the National Cardiac Arrest Registry to Enhance Survival and Medicare Annual Dialysis Facility Report registries from 2013 to 2017. We identified patients experiencing cardiac arrests within US outpatient dialysis clinics via geolocation matching ( N =1554). Differences in facility size, quality, staffing, and patient-related factors were summarized and compared according to patient race. Multilevel multivariable logistic regression models including these factors were used to examine the influence of these factors on the observed disparity in CPR rates between Black and White patients., Results: Compared with White patients, Black cardiac arrest patients dialyzed in larger facilities (26 versus 21 dialysis stations; P <0.001), facilities with fewer registered nurses per station (0.29 versus 0.33; P <0.001), and facilities with lower quality scores (# citations 6.8 versus 6.3; P =0.04). Facilities treating Black patients cared for a higher proportion of patients with a history of cardiac arrest (41% versus 35%; P <0.001), HIV/hepatitis B, and Medicaid-enrolled patients (15% versus 11%; P <0.001). Even after accounting for these differences and other covariates, the racial disparity for CPR in Black versus White patients persisted (OR=0.45; 95% CI, 0.27 to 0.75). The racial disparity in CPR was greater among older patients compared with younger patients (interaction P =0.04)., Conclusions: The racial disparity in CPR delivery within dialysis clinics was not explained by differences in facility resources and quality. Reducing this disparity will require a multifaceted approach, including developing dialysis clinic-specific protocols for CPR and addressing potential implicit bias., Competing Interests: M.E. Dupre reports honoraria from Springer Nature. P.H. Pun has received investigator-initiated research funding unrelated to this project from Medtronic, honoraria from the American Society of Nephrology and the National Kidney Foundation, and consulting fees from AstraZeneca, Ardelyx, Fresenius Kidney Care, North America, Janssen, and Vifor. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Background: Undergoing percutaneous coronary intervention (PCI) is a risk factor for AKI development, but few studies have quantified racial differences in AKI incidence after this procedure., Methods: We examined the association of self-reported race (Black, White, or other) and baseline eGFR with AKI incidence among patients who underwent PCI at Duke University Medical Center between January 1, 2003, and December 31, 2013. We defined AKI as a 0.3 mg/dl absolute increase in serum creatinine within 48 hours, or ≥1.5-fold relative elevation within 7 days post-PCI from the reference value ascertained within 30 days before PCI., Results: Of 9422 patients in the analytic cohort (median age 63 years; 33% female; 75% White, 20% Black, 5% other race), 9% developed AKI overall (14% of Black, 8% of White, 10% of others). After adjustment for demographics, socioeconomic status, comorbidities, predisposing medications, PCI indication, periprocedural AKI prophylaxis, and PCI procedural characteristics, Black race was associated with increased odds for incident AKI compared with White race (odds ratio [OR], 1.79; 95% confidence interval [95% CI], 1.48 to 2.15). Compared with Whites, odds for incident AKI were not significantly higher in other patients (OR, 1.30; 95% CI, 0.93 to 1.83). Low baseline eGFR was associated with graded, higher odds of AKI incidence ( P value for trend <0.001); however, there was no interaction between race and baseline eGFR on odds for incident AKI ( P value for interaction = 0.75)., Conclusions: Black patients had greater odds of developing AKI after PCI compared with White patients. Future investigations should identify factors, including multiple domains of social determinants, that predispose Black individuals to disparate AKI risk after PCI., (Copyright © 2021 by the American Society of Nephrology.)

Competing Interests: P.H. Pun reports personal fees from AstraZeneca, Fresenius Medical Care, Janssen Pharmaceuticals, and Relypsa, outside the submitted work. The remaining author has nothing to disclose.