Publications by authors named "Esther D Kim"

17 Publications

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Functional outcomes of sleep predict cardiovascular intermediary outcomes and all-cause mortality in incident hemodialysis patients.

J Clin Sleep Med 2021 Mar 29. Epub 2021 Mar 29.

Department of Medicine, The Miriam Hospital, Warren Alpert Medical School of Brown University, Providence, RI.

Study Objectives: Patients with end-stage kidney disease (ESKD) commonly experience sleep disturbances. Sleep disturbance has been inconsistently associated with mortality risk in hemodialysis patients, but the burden of symptoms from sleep disturbances has emerged as a marker that may shed light on these discrepancies and guide treatment decisions. This study examines whether functional outcomes of sleep are associated with increased risk of intermediary CV outcomes or mortality among adults initiating hemodialysis.

Methods: In 228 participants enrolled in the Predictors of Arrhythmic and Cardiovascular risk in ESRD (PACE) study, the Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), which assesses functional outcomes of daytime sleepiness, was administered within 6 months of enrollment. Intermediary CV outcomes included QTc [ms], heart rate variance [ms²], left ventricular mass index [g/m², LVMI], and left ventricular hypertrophy [LVH]. The association of FOSQ-10 score with all-cause mortality was examined using proportional hazards regression. Results: Mean age was 55 years, median BMI was 28 kg/m² (IQR 24,33), with 70% African Americans. Median FOSQ-10 score was 19.7 (IQR: 17.1,20.0). A 10% lower FOSQ-10 score was associated with increased mortality risk (HR 1.09, 95%CI 1.01-1.18). Lower FOSQ-10 scores were associated with longer QTc duration and lower heart rate variance, but not LVMI or LVH.

Conclusions: In adults initiating dialysis, sleep-related functional impairment is common and is associated with intermediary cardiovascular disease measures and increased mortality risk. Future studies should assess the impact of screening for sleep disturbances in ESKD patients to identify individuals at increased risk for cardiovascular complications and death.
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http://dx.doi.org/10.5664/jcsm.9304DOI Listing
March 2021

What Are the Burden, Causes, and Costs of Early Hospital Readmissions After Kidney Transplantation?

Prog Transplant 2021 Jun 24;31(2):160-167. Epub 2021 Mar 24.

Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Introduction: Kidney transplant recipients are at risk for complications resulting in early hospital readmission. This study sought to determine the incidences, risk factors, causes, and financial costs of early readmissions.

Design: This single-centre cohort study included 1461 kidney recipients from 1 Jul 2004 to 31 Dec 2012, with at least 1-year follow-up. Early readmission was defined as hospitalization within 30 or 90-days postdischarge from transplant admission. Associations between various parameters and 30 and 90-days posttransplant were determined using multivariable Cox proportional hazards models. The hospital-associated costs of were assessed.

Results: The rates of early readmission were 19.4% at 30 days and 26.8% at 90 days posttransplant. Mean cost per 30-day readmission was 11 606 CAD. Infectious complications were the most common reasons and resulted in the greatest cost burden. Factors associated with 30 and 90-days in multivariable models were recipient history of chronic lung disease (hazard ratio or HR 1.78 [95%CI: 1.14, 2.76] and HR 1.68 [1.14, 2.48], respectively), median time on dialysis (HR 1.07 [95% CI: 1.01, 1.13]and HR 1.06 [95% CI: 1.01, 1.11], respectively), being transplanted preemptively (HR 1.75 [95% CI: 1.07, 2.88] and HR 1.66 [95% CI: 1.07, 2.57], respectively), and having a transplant hospitalization lasting of and more than 11 days (HR 1.52 [95% CI: 1.01, 2.27] and HR 1.65 [95% CI: 1.16, 2.34], respectively).

Discussion: Early hospital readmission after transplantation was common and costly. Strategies to reduce the burden of early hospital readmissions are needed for all patients.
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http://dx.doi.org/10.1177/15269248211003563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182333PMC
June 2021

Two-Week Burden of Arrhythmias across CKD Severity in a Large Community-Based Cohort: The ARIC Study.

J Am Soc Nephrol 2021 03 28;32(3):629-638. Epub 2021 Jan 28.

Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.

Background: CKD is associated with sudden cardiac death and atrial fibrillation (AF). However, other types of arrhythmia and different measures of the burden of arrhythmias, such as presence and frequency, have not been well characterized in CKD.

Methods: To quantify the burden of arrhythmias across CKD severity in 2257 community-dwelling adults aged 71-94 years, we examined associations of major arrhythmias with CKD measures (eGFR and albuminuria) among individuals in the Atherosclerosis Risk in Communities study. Participants underwent 2 weeks of noninvasive, single-lead electrocardiogram monitoring. We examined types of arrhythmia burden: presence and frequency of arrhythmias and percent time in arrhythmias.

Results: Of major arrhythmias, there was a higher prevalence of AF and nonsustained ventricular tachycardia among those with more severe CKD, followed by long pause (>30 seconds) and atrioventricular block. Nonsustained ventricular tachycardia was the most frequent major arrhythmia (with 4.2 episodes per person-month). Most participants had ventricular ectopy, supraventricular tachycardia, and supraventricular ectopy. Albuminuria consistently associated with higher AF prevalence and percent time in AF, and higher prevalence of nonsustained ventricular tachycardia. When other types of arrhythmic burden were examined, lower eGFR was associated with a lower frequency of atrioventricular block. Although CKD measures were not strongly associated with minor arrhythmias, higher albuminuria was associated with a higher frequency of ventricular ectopy.

Conclusions: CKD, especially as measured by albuminuria, is associated with a higher burden of AF and nonsustained ventricular tachycardia. Additionally, eGFR is associated with less frequent atrioventricular block, whereas albuminuria is associated with more frequent ventricular ectopy. Use of a novel, 2-week monitoring approach demonstrated a broader range of arrhythmias associated with CKD than previously reported.
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http://dx.doi.org/10.1681/ASN.2020030301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920167PMC
March 2021

Calcification Biomarkers, Subclinical Vascular Disease, and Mortality Among Multiethnic Dialysis Patients.

Kidney Int Rep 2020 Oct 6;5(10):1729-1737. Epub 2020 Aug 6.

Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.

Introduction: Vascular calcification and stiffness are associated with higher mortality and cardiovascular disease in hemodialysis patients, but the underlying mechanism is not well elucidated and previous studies have been contradictory. We sought to determine the association of circulating calcification biomarkers with calcification, stiffness, and mortality in a multiethnic incident dialysis population.

Methods: Among 391 incident hemodialysis participants enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study, we examined the cross-sectional associations of baseline fibroblast growth factor 23 (FGF23), desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), fetuin-A, and osteoprotegerin (OPG) according to total coronary artery calcium score (CAC, using the Agatston calcification criteria) at baseline, vascular stiffness (pulse wave velocity [PWV]) over 4 study visits, and all-cause mortality.

Results: Patients' mean age was 55 years; 40% were female, 72% were African American, and 58% had diabetes. Higher OPG and FGF23 were associated with a 1.09-fold (per 5-pmol/l increase in OPG; 95% confidence interval [CI]: 1.01-1.17) and 1.12-fold (per increase of 100 log RU/ml in FGF23; 95% CI: 1.02‒1.34) higher prevalence of CAC, independent of demographics, comorbidities, dialysis factors, and serum klotho levels. Higher OPG was associated with higher baseline PWV. Higher FGF23 was associated with lower PWV over follow-up. dp-ucMGP and fetuin-A were not associated with either CAC or vascular stiffness. After adjustment, circulating biomarkers were not associated with mortality risk.

Conclusion: Several circulating calcification biomarkers were only modestly associated with subclinical cardiovascular disease in an incident multiethnic hemodialysis population; none were associated with mortality. Understanding whether these associations persist in larger, diverse hemodialysis populations is warranted before planning trials.
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http://dx.doi.org/10.1016/j.ekir.2020.07.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569684PMC
October 2020

Short-Term Prognostic Impact of Arterial Stiffness in Older Adults Without Prevalent Cardiovascular Disease.

Hypertension 2019 12 4;74(6):1373-1382. Epub 2019 Nov 4.

From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (E.D.K., S.H.B., J.C., K.M.).

Arterial stiffness, represented as carotid-femoral pulse wave velocity (cfPWV), predicts cardiovascular disease (CVD). In older populations, however, this association seems attenuated. Moreover, the prognostic values of pulse wave velocity at different arterial segments and newer parameters like cardio-ankle vascular index (CAVI) remain unclear, especially in US older adults. In 3034 Atherosclerosis Risk in Communities (ARIC) study participants (66-90 years) without CVD, we examined the associations of 4 pulse wave velocity measures (cfPWV, heart-femoral, brachial-ankle, heart-ankle) and 2 new measures of arterial stiffness (CAVI and cardio-femoral vascular index derived from heart-ankle and heart-femoral, respectively) with incident CVD (coronary disease, stroke, and heart failure) and all-cause mortality. Over a median follow-up of 4.4 years, there were 168 incident CVD events and 244 deaths. Overall, stiffness measures did not show strong associations with CVD, except cfPWV, which demonstrated a J-shaped association even after adjusting for potential confounders (hazard ratio, 1.83 [95% CI, 1.08-3.09] in top quartile and 1.97 [1.14-3.39] in bottom quartile versus second bottom quartile). When each CVD was examined separately, heart failure was most robustly associated with higher cfPWV, and stroke was strongly associated with lower cfPWV. There were no significant associations with all-cause mortality. Among different measures of pulse wave velocity, cfPWV showed the strongest associations with CVD, especially heart failure, in older adults without CVD. Other pulse wave velocity measures had no strong associations. Our findings further support cfPWV as the index measure of arterial stiffness and the link of arterial stiffness to heart failure development but also suggest somewhat limited prognostic value of arterial stiffness in older adults overall.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110414PMC
December 2019

Hemodialysis Procedure-Associated Autonomic Imbalance and Cardiac Arrhythmias: Insights From Continuous 14-Day ECG Monitoring.

J Am Heart Assoc 2019 10 28;8(19):e013748. Epub 2019 Sep 28.

Oregon Health & Science University Portland OR.

Background In patients with end-stage kidney disease, sudden cardiac death is more frequent after a long interdialytic interval, within 6 hours after the end of a hemodialysis session. We hypothesized that the occurrence of paroxysmal arrhythmias is associated with changes in heart rate and heart rate variability in different phases of hemodialysis. Methods and Results We conducted a prospective ancillary study of the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease cohort. Continuous ECG monitoring was performed using an ECG patch, and short-term heart rate variability was measured for 3 minutes every hour (by root mean square of the successive normal-to-normal intervals, spectral analysis, Poincaré plot, and entropy), up to 300 hours. Out of enrolled participants (n=28; age 54±13 years; 57% men; 96% black; 33% with a history of cardiovascular disease; left ventricular ejection fraction 70±9%), arrhythmias were detected in 13 (46%). Nonsustained ventricular tachycardia occurred more frequently during/posthemodialysis than pre-/between hemodialysis (63% versus 37%, =0.015). In adjusted for cardiovascular disease time-series analysis, nonsustained ventricular tachycardia was preceded by a sudden heart rate increase (by 11.2 [95% CI 10.1-12.3] beats per minute; <0.0001). During every-other-day dialysis, root mean square of the successive normal-to-normal intervals had a significant circadian pattern (Mesor 10.6 [ 95% CI 0.9-11.2] ms; amplitude 1.5 [95% CI 1.0-3.1] ms; peak at 02:01 [95% CI 20:22-03:16] am; <0.0001), which was replaced by a steady worsening on the second day without dialysis (root mean square of the successive normal-to-normal intervals -1.41 [95% CI -1.67 to -1.15] ms/24 h; <0.0001). Conclusions Sudden increase in heart rate during/posthemodialysis is associated with nonsustained ventricular tachycardia. Every-other-day hemodialysis preserves circadian rhythm, but a second day without dialysis is characterized by parasympathetic withdrawal.
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http://dx.doi.org/10.1161/JAHA.119.013748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806026PMC
October 2019

Associations of serum and dialysate electrolytes with QT interval and prolongation in incident hemodialysis: the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease (PACE) study.

BMC Nephrol 2019 04 18;20(1):133. Epub 2019 Apr 18.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Background: Prolonged QT interval in hemodialysis patients may be associated with sudden cardiac death, however, few studies examined the longitudinal associations of modifiable factors such as serum and dialysate concentrations of calcium, potassium, and magnesium with corrected QT (QTc) prolongation in incident hemodialysis patients.

Methods: In 330 in-center hemodialysis participants from the PACE study who were followed up for one year, we examined the associations of predialysis serum electrolytes (total calcium [Ca], corrected Ca [cCa], ionized Ca [iCa], potassium [K], magnesium [Mg]), dialysate (dCa and dK), and serum-to-dialysate gradient measures with QTc interval and prolongation (≥460 ms in women and ≥ 450 ms in men).

Results: At the first study visit, 47% had QTc prolongation. Lower iCa and K were associated with longer QTc interval independent of potential confounders (QTc difference = 8.55[95% CI: 2.13, 14.97] ms for iCa; QTc difference = 9.89[1.58, 18.20] ms for K). Lower iCa was also associated with a higher risk of QTc prolongation. At 1 year of follow-up, 31% had persistent QTc prolongation. In longitudinal analyses, the associations of iCa and K with QTc interval remained significant, and lower K was associated with a higher risk of QTc prolongation while the association of iCa with QTc prolongation was borderline statistically significant. Serum Mg, dCa or dK, and respective gradients were not associated with QTc interval or prolongation.

Conclusion: Prolonged QTc is very common in incident hemodialysis participants and persists over follow-up. Ionized Ca and K are consistently inversely associated with QTc prolongation, which suggests closer monitoring for a low calcium or potassium level to mitigate risk.
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http://dx.doi.org/10.1186/s12882-019-1282-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474045PMC
April 2019

Central and peripheral pulse wave velocity and subclinical myocardial stress and damage in older adults.

PLoS One 2019 27;14(2):e0212892. Epub 2019 Feb 27.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.

Background: Arterial stiffness independently predicts cardiovascular disease. However, few studies have evaluated the associations of central and peripheral pulse wave velocity (PWV) with biomarkers of both myocardial stress (natriuretic peptide [NT-proBNP]) and damage (high-sensitivity cardiac troponin-T [hs-cTnT]) among persons without cardiac disease.

Methods: We examined 3,348 participants (67-90 years) without prevalent cardiac disease in the Atherosclerosis Risk in Communities (ARIC) Study (2011-13). The cross-sectional associations of PWV quartiles for central arterial segments (carotid-femoral, heart-carotid, heart-femoral) and peripheral artery (femoral-ankle) with NT-proBNP and hs-cTnT were evaluated accounting for potential confounders.

Results: Most PWV measures demonstrated J- or U-shaped associations with the two cardiac biomarkers. The highest (Q4) vs. second lowest (Q2) quartile of central PWV measures (carotid-femoral, heart-carotid, heart-femoral PWV) were associated with higher levels of NT-proBNP independently of demographic characteristics. The associations were less evident for hs-cTnT. These associations were attenuated after adjusting for traditional cardiovascular risk factors, but the heart-carotid PWV-NT-proBNP relationship remained borderline significant (difference in log-NT-proBNP = 0.08 [-0.01, 0.17] in Q4 vs. Q2, p = 0.07). Peripheral PWV demonstrated inverse associations. Higher values of NT-proBNP were seen in the lowest vs. second lowest quartile of all PWV measures.

Conclusions: Central stiffness measures showed stronger associations with cardiac biomarkers (particularly NT-proBNP) than peripheral measures among older adults without cardiac disease. Our findings are consistent with the concept of ventricular-vascular coupling and suggest that central rather than peripheral arterial hemodynamics are more closely related to myocardial stress rather than damage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212892PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392306PMC
November 2019

Cardio-ankle vascular index and cardiovascular disease: Systematic review and meta-analysis of prospective and cross-sectional studies.

J Clin Hypertens (Greenwich) 2019 01 19;21(1):16-24. Epub 2018 Nov 19.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennysylvania.

The cardio-ankle vascular index (CAVI) is a new measure of arterial stiffness that reflects the stiffness from the ascending aorta to the ankle arteries, and demonstrates little dependence on blood pressure during the evaluation. However, a comprehensive assessment of the association of CAVI with cardiovascular disease (CVD) has not been reported. We performed a systematic review to assess the association between CAVI and CVD. We searched for both prospective and cross-sectional studies using MEDLINE, Embase, and Cochrane from inception until April 11, 2017. We pooled the results using random-effects models. Among 1519 records, we identified nine prospective studies (n = 5214) and 17 cross-sectional eligible studies (n = 7309), with most enrolling high CVD risk populations in Asia. All nine prospective studies investigated composite CVD events as an outcome (498 cases including coronary events and stroke) but modeled CAVI inconsistently. The pooled adjusted hazard ratio for CVD events per 1 standard deviation increment of CAVI in four studies was 1.20 (95% CI: 1.05-1.36, P = 0.006). Of the 17 cross-sectional studies, 13 studies compared CAVI values between patients with and without CVD and all reported significantly higher values in those with CVD (pooled mean difference in CAVI values 1.28 [0.86-1.70], P < 0.001). This systematic review suggests a modest association between CAVI and incident CVD risk, and highlights the need for studies assessing CAVI as a predictor of CVD in the general population and non-Asian countries.
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http://dx.doi.org/10.1111/jch.13425DOI Listing
January 2019

Obstructive Sleep Apnea Increases Sudden Cardiac Death in Incident Hemodialysis Patients.

Am J Nephrol 2018 15;48(2):147-156. Epub 2018 Aug 15.

Department of Medicine, Divisions of Pulmonary, Critical Care and Sleep Medicine, and Obstetric Medicine, The Miriam Hospital and Alpert Medical School of Brown University, Providence, Rhode Island, USA.

Background: Mortality in end-stage renal disease (ESRD) occurs predominantly from cardiovascular disease (CVD) and sudden cardiac death (SCD). Obstructive sleep apnea (OSA) is characterized by periodic airflow limitation associated with sleep arousal and oxygen desaturation and is prevalent in patients with ESRD. Whether OSA increases the risk for SCD, cardiovascular and all-cause mortality among hemodialysis patients remains unknown.

Methods: In a prospective cohort of 558 incident hemodialysis patients, we examined the association of OSA with all-cause mortality, cardiovascular mortality, and SCD using Cox proportional hazards models controlling for traditional CVD risk factors.

Results: Sixty-six incident hemodialysis patients (12%) had OSA. Mean age (56 years) and percentage of males (56%) were identical in OSA and no-OSA groups. Fewer African Americans had OSA than non-African Americans (9 vs. 18%, respectively). Participants with OSA had higher body-mass index, Charlson comorbidity score, and left ventricular mass index and greater prevalence of diabetes and coronary artery disease. During 1,080 person-years of follow-up, 104 deaths occurred, 29% of which were cardiovascular. OSA was associated with a higher risk of all-cause mortality (HR 1.90 [95% CI 1.04-3.46]) and cardiovascular mortality (HR 3.62 [95% CI 1.36-9.66]) after adjusting for demographics and body-mass index. OSA was associated with a higher risk of SCD after adjusting for demographics (HR 3.28 [95% CI 1.12-9.57]) and multiple cardiovascular risk factors.

Conclusions: Incident hemodialysis patients with OSA are at increased risk of all-cause and cardiovascular mortality and SCD. Future studies should assess the impact of screening for OSA and OSA-targeted interventions on mortality in ESRD.
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http://dx.doi.org/10.1159/000489963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519703PMC
November 2019

Associations Between Kidney Disease Measures and Regional Pulse Wave Velocity in a Large Community-Based Cohort: The Atherosclerosis Risk in Communities (ARIC) Study.

Am J Kidney Dis 2018 11 12;72(5):682-690. Epub 2018 Jul 12.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD. Electronic address:

Rationale & Objective: Arterial stiffness is suggested as a mediator of cardiorenal interaction. However, previous studies reported inconsistent associations between chronic kidney disease (CKD) and arterial stiffness and were limited by using either estimated glomerular filtration rate (eGFR) or albumin-creatinine ratio (ACR) and examining arterial stiffness at limited segments.

Study Design: Cross-sectional.

Setting & Participants: 3,424 Atherosclerosis in Communities (ARIC) Study participants aged 66 to 90 years during 2011 to 2013.

Predictors: eGFR and ACR.

Outcome: Pulse wave velocity (PWV) at 6 segments: carotid-femoral (cfPWV), heart-carotid (hcPWV), and heart-femoral (hfPWV), reflecting central stiffness; heart-ankle (haPWV) and brachial-ankle (baPWV), representing both central and peripheral stiffness; and femoral-ankle (faPWV), indicating peripheral stiffness.

Analytical Approach: Multiple linear and logistic regression models to quantify the associations of eGFR and ACR with continuous PWV and elevated PWV (in the highest quartile), respectively.

Results: After adjusting for age, sex, and race, higher cfPWV and hfPWV were consistently associated with lower eGFR and higher ACR. Higher haPWV and baPWV were also observed with higher ACR. The independent association of both CKD measures with elevated cfPWV remained consistent after adjusting for additional confounders (ORs of elevated cfPWV were 1.09 [95% CI, 1.01-1.18] per 15-mL/min/1.73m lower eGFR and 1.20 [95% CI, 1.07-1.33] per 4-fold higher ACR). Higher ACR was also associated with elevated hfPWV and haPWV (ORs per 4-fold higher ACR were 1.25 [95% CI, 1.12-1.39] for elevated hfPWV and 1.19 [95% CI, 1.06-1.33] for elevated haPWV). Lower eGFR was associated with lower odds of elevated baPWV and faPWV (ORs per 15-mL/min/1.73m lower eGFR were 0.92 [95% CI, 0.84-0.99] and 0.91 [95% CI, 0.85-0.99], respectively).

Limitation: Unable to address temporality between CKD measures and arterial stiffness.

Conclusions: Both lower eGFR and higher ACR are independently associated with measures of central arterial stiffness, with stronger associations for ACR over eGFR. Our findings suggest that central arterial stiffness may be an important pathophysiologic phenotype of vascular disease in CKD.
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http://dx.doi.org/10.1053/j.ajkd.2018.04.018DOI Listing
November 2018

Association of Arterial Stiffness and Central Pressure With Cognitive Function in Incident Hemodialysis Patients: The PACE Study.

Kidney Int Rep 2017 Nov 3;2(6):1149-1159. Epub 2017 Aug 3.

Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

Introduction: Cognitive impairment commonly occurs in hemodialysis patients, with vascular disease potentially implicated in its pathogenesis. However, the relationship of detailed vascular assessment with cognitive function in patients new to hemodialysis has not been demonstrated.

Methods: In a prospective study of incident hemodialysis participants enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in ESRD (PACE) study, we determined aortic stiffness by pulse-wave velocity (PWV), systemic arterial stiffness by the augmentation index (AIx) and central pulse pressure (cPP), and examined their associations with cognitive processing speed, executive function, and global cognitive impairment measured by the Trail making test A (TMTA), Trail making test B (TMTB), and the modified Mini-Mental State Exam (3MS).

Results: Mean baseline age was 55 ± 13 years, 58% were male, 72% were African American, 35% had coronary artery disease, 55% had diabetes, and 10% had cognitive impairment. At baseline, higher PWV and cPP were associated with a longer TMTA, and a higher PWV was associated with a longer TMTB, but the associations were attenuated after multivariable adjustment. At 1 year, PWV was not independently associated with TMTA, TMTB, or 3MS. However, unadjusted and adjusted analyses revealed every 10% increase in AIx and 10 mm Hg increase in cPP were associated with longer TMTB (time difference: 0.14; 95% confidence interval [CI]: 0.02-0.25 log-seconds; time difference: 0.11; 95% CI: 0.05-0.17 log-seconds) and global cognitive impairment (odds ratio [OR]: 10.23; 95% CI: 1.77-59.00; OR: 2.88; 95% CI: 1.48-5.59).

Discussion: Higher AIx and cPP, which are indicative of abnormal wave reflections in distal vessels, are associated with, and might contribute to, declining cognitive function in patients starting hemodialysis.
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http://dx.doi.org/10.1016/j.ekir.2017.07.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733684PMC
November 2017

Incidence of hyperglycemia and diabetes and association with electrolyte abnormalities in pediatric solid organ transplant recipients.

Nephrol Dial Transplant 2017 Sep;32(9):1579-1586

Department of Pediatrics, Division of Pediatric Nephrology, Hospital for Sick Children, Toronto, ON, Canada.

Background: Posttransplant hyperglycemia is an important predictor of new-onset diabetes after transplantation, and both are associated with significant morbidity and mortality. Precise estimates of posttransplant hyperglycemia and diabetes in children are unknown. Low magnesium and potassium levels may also lead to diabetes after transplantation, with limited evidence in children.

Methods: We conducted a cohort study of 451 pediatric solid organ transplant recipients to determine the incidence of hyperglycemia and diabetes, and the association of cations with both endpoints. Hyperglycemia was defined as random blood glucose levels ≥11.1 mmol/L on two occasions after 14 days of transplant not requiring further treatment. Diabetes was defined using the American Diabetes Association Criteria. For magnesium and potassium, time-fixed, time-varying and rolling average Cox proportional hazards models were fitted to evaluate the association with hyperglycemia and diabetes.

Results: Among 451 children, 67 (14.8%) developed hyperglycemia and 27 (6%) progressed to diabetes at a median of 52 days (interquartile range 22-422) from transplant. Multi-organ recipients had a 9-fold [hazard ratio (HR) 8.9; 95% confidence interval (CI) 3.2-25.2] and lung recipients had a 4.5-fold (HR 4.5; 95% CI 1.8-11.1) higher risk for hyperglycemia and diabetes, respectively, compared with kidney transplant recipients. Both magnesium and potassium had modest or no association with the development of hyperglycemia and diabetes.

Conclusions: Hyperglycemia and diabetes occur in 15 and 6% children, respectively, and develop early posttransplant with lung or multi-organ transplant recipients at the highest risk. Hypomagnesemia and hypokalemia do not confer significantly greater risk for hyperglycemia or diabetes in children.
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http://dx.doi.org/10.1093/ndt/gfx205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837606PMC
September 2017

Electrophysiologic Substrate and Risk of Mortality in Incident Hemodialysis.

J Am Soc Nephrol 2016 Nov 29;27(11):3413-3420. Epub 2016 Apr 29.

Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada;

The single leading cause of mortality on hemodialysis is sudden cardiac death. Whether measures of electrophysiologic substrate independently associate with mortality is unknown. We examined measures of electrophysiologic substrate in a prospective cohort of 571 patients on incident hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease Study. A total of 358 participants completed both baseline 5-minute and 12-lead electrocardiogram recordings on a nondialysis day. Measures of electrophysiologic substrate included ventricular late potentials by the signal-averaged electrocardiogram and spatial mean QRS-T angle measured on the averaged beat recorded within a median of 106 days (interquartile range, 78-151 days) from dialysis initiation. The cohort was 59% men, and 73% were black, with a mean±SD age of 55±13 years. Transthoracic echocardiography revealed a mean±SD ejection fraction of 65.5%±12.0% and a mean±SD left ventricular mass index of 66.6±22.3 g/m During 864.6 person-years of follow-up, 77 patients died; 35 died from cardiovascular causes, of which 15 were sudden cardiac deaths. By Cox regression analysis, QRS-T angle ≥75° significantly associated with increased risk of cardiovascular mortality (hazard ratio, 2.99; 95% confidence interval, 1.31 to 6.82) and sudden cardiac death (hazard ratio, 4.52; 95% confidence interval, 1.17 to 17.40) after multivariable adjustment for demographic, cardiovascular, and dialysis factors. Abnormal signal-averaged electrocardiogram measures did not associate with mortality. In conclusion, spatial QRS-T angle but not abnormal signal-averaged electrocardiogram significantly associates with cardiovascular mortality and sudden cardiac death independent of traditional risk factors in patients starting hemodialysis.
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http://dx.doi.org/10.1681/ASN.2015080916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084888PMC
November 2016

Membranous Nephropathy: Quantifying Remission Duration on Outcome.

J Am Soc Nephrol 2017 Mar 18;28(3):995-1003. Epub 2016 Oct 18.

Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada; and.

Although change in proteinuria has been proposed as a surrogate for long-term prognosis in membranous nephropathy (MGN), variability in proteinuria levels and lag between these changes and acceptable end points, such as ESRD, has limited its utility. This cohort study examined the prognostic significance of remission duration in 376 patients with biopsy-proven idiopathic/primary MGN who achieved a remission after a period of nephrotic-range proteinuria. We defined complete remission (CR), partial remission (PR), and relapse as proteinuria ≤0.3, 0.4-3.4, and ≥3.5 g/d after CR or PR, respectively. The exposure variable was the remission status of patients at fixed landmarks (3, 6, 12, 24, and 36 months) after the date of first remission. The primary outcome was ESRD or 50% reduction in eGFR. We fitted Cox proportional hazards models to examine the association of remission status at each landmark and the primary end point. Persistent remission associated with unadjusted hazard ratios for the primary outcome that ranged by landmark from 0.35 (95% confidence interval, 0.20 to 0.61) to 0.56 (95% confidence interval, 0.31 to 1.04). Separate analyses for PR and CR yielded similar results. After adjustment, maintaining remission associated with significantly reduced risk of the primary outcome at all landmarks. Durable remissions associated with improved renal survival. Although the longer the remission, the greater the improvement, patients with remission durations as short as 3 months had improved renal prognosis compared with patients who relapsed. This study validates and quantifies PR and CR as surrogates for long-term outcome in MGN.
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http://dx.doi.org/10.1681/ASN.2015111262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328151PMC
March 2017

Calcium and Sudden Cardiac Death in End-Stage Renal Disease.

Semin Dial 2015 Nov-Dec;28(6):624-35. Epub 2015 Aug 9.

Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Sudden cardiac death (SCD) accounts for a quarter of all deaths in end-stage renal disease (ESRD) patients. While causative mechanisms of SCD in this high risk population remain poorly defined, interaction of the vulnerable myocardium with dialysis-related arrhythmic triggers is thought to play a major role. Recent evidence suggests that dialysis-induced derangement of calcium concentrations contributes to the increased risk of all-cause and cardiovascular mortality, vascular calcification, and SCD. Current KDIGO guidelines recommend avoiding high dialysate calcium concentrations as a precaution against adverse outcomes of increased calcium burden and vascular calcification. Conversely, low calcium concentration is also implicated in the development of SCD via increased QT dispersion and prolonged QT interval. Consequently, the optimal dialysate calcium concentration in dialysis patients remains debated and further studies are needed to establish the best strategy for managing calcium in dialysis patients.
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http://dx.doi.org/10.1111/sdi.12419DOI Listing
August 2016

Cross-sectional association of volume, blood pressures, and aortic stiffness with left ventricular mass in incident hemodialysis patients: the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease (PACE) study.

BMC Nephrol 2015 Aug 7;16:131. Epub 2015 Aug 7.

Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Background: Higher left ventricular mass (LV) strongly predicts cardiovascular mortality in hemodialysis patients. Although several parameters of preload and afterload have been associated with higher LV mass, whether these parameters independently predict LV mass, remains unclear.

Methods: This study examined a cohort of 391 adults with incident hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study. The main exposures were systolic and diastolic blood pressure (BP), pulse pressure, arterial stiffness by pulse wave velocity (PWV), volume status estimated by pulmonary pressures using echocardiogram and intradialytic weight gain. The primary outcome was baseline left ventricular mass index (LVMI).

Results: Each systolic, diastolic blood, and pulse pressure measurement was significantly associated with LVMI by linear regression regardless of dialysis unit BP or non-dialysis day BP measurements. Adjusting for cardiovascular confounders, every 10 mmHg increase in systolic or diastolic BP was significantly associated with higher LVMI (SBP β = 7.26, 95 % CI: 4.30, 10.23; DBP β = 10.05, 95 % CI: 5.06, 15.04), and increased pulse pressure was also associated with higher LVMI (β = 0.71, 95 % CI: 0.29, 1.13). Intradialytic weight gain was also associated with higher LVMI but attenuated effects after adjustment (β = 3.25, 95 % CI: 0.67, 5.83). PWV and pulmonary pressures were not associated with LVMI after multivariable adjustment (β = 0.19, 95 % CI: -1.14, 1.79; and β = 0.10, 95 % CI: -0.51, 0.70, respectively). Simultaneously adjusting for all main exposures demonstrated that higher BP was independently associated with higher LVMI (SBP β = 5.64, 95 % CI: 2.78, 8.49; DBP β = 7.29, 95 % CI: 2.26, 12.31, for every 10 mmHg increase in BP).

Conclusions: Among a younger and incident hemodialysis population, higher systolic, diastolic, or pulse pressure, regardless of timing with dialysis, is most associated with higher LV mass. Future studies should consider the use of various BP measures in examining the impact of BP on LVM and cardiovascular disease. Findings from such studies could suggest that high BP should be more aggressively treated to promote LVH regression in incident hemodialysis patients.
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http://dx.doi.org/10.1186/s12882-015-0131-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528691PMC
August 2015
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