Browsing by Author "Wolf, Myles"
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Item Open Access Association between patient race and staff resuscitation efforts after cardiac arrest in outpatient dialysis clinics: A study from the CARES surveillance group.(Resuscitation, 2020-08-27) Hofacker, Samuel A; Dupre, Matthew E; Vellano, Kimberly; McNally, Bryan; Starks, Monique Anderson; Wolf, Myles; Svetkey, Laura P; Pun, Patrick HBACKGROUND: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.Item Open Access Chicago supermarket data and food access analytics in census tract shapefiles for 2007–2014(Data in Brief, 2018-12-01) Kolak, Marynia; Bradley, Michelle; Block, Daniel; Pool, Lindsay; Garg, Gaurang; Toman, Chrissy Kelly; Boatright, Kyle; Lipiszko, Dawid; Koschinsky, Julia; Kershaw, Kiarri; Carnethon, Mercedes; Isakova, Tamara; Wolf, Myles© 2018 The Authors Longitudinal analysis of supermarkets over time is essential to understanding the dynamics of foodscape environments for healthy living. Supermarkets for 2007, 2011, and 2014 for the City of Chicago were curated and further validated. The average distance to all supermarkets along the street network was constructed for each resident-populated census tract. These analytic results were generated with GIS software and stored as spatially enabled data files, facilitating further research and analysis. The data presented in this article are related to the research article entitled “Urban foodscape trends: Disparities in healthy food access in Chicago, 2007–2014” (Kolak et al., 2018).Item Open Access Creatinine- versus cystatin C-based renal function assessment in the Northern Manhattan Study.(PloS one, 2018-01) Husain, S Ali; Willey, Joshua Z; Park Moon, Yeseon; Elkind, Mitchell SV; Sacco, Ralph L; Wolf, Myles; Cheung, Ken; Wright, Clinton B; Mohan, SumitBACKGROUND:Accurate glomerular filtration rate estimation informs drug dosing and risk stratification. Body composition heterogeneity influences creatinine production and the precision of creatinine-based estimated glomerular filtration rate (eGFRcr) in the elderly. We compared chronic kidney disease (CKD) categorization using eGFRcr and cystatin C-based estimated GFR (eGFRcys) in an elderly, racially/ethnically diverse cohort to determine their concordance. METHODS:The Northern Manhattan Study (NOMAS) is a predominantly elderly, multi-ethnic cohort with a primary aim to study cardiovascular disease epidemiology. We included participants with concurrently measured creatinine and cystatin C. eGFRcr was calculated using the CKD-EPI 2009 equation. eGFRcys was calculated using the CKD-EPI 2012 equation. Logistic regression was used to estimate odds ratios and 95% confidence intervals of factors associated with reclassification from eGFRcr≥60ml/min/1.73m2 to eGFRcys<60ml/min/1.73m2. RESULTS:Participants (n = 2988, mean age 69±10yrs) were predominantly Hispanic, female, and overweight/obese. eGFRcys was lower than eGFRcr by mean 23mL/min/1.73m2. 51% of participants' CKD status was discordant, and only 28% maintained the same CKD stage by both measures. Most participants (78%) had eGFRcr≥60mL/min/1.73m2; among these, 64% had eGFRcys<60mL/min/1.73m2. Among participants with eGFRcr≥60mL/min/1.73m2, eGFRcys-based reclassification was more likely in those with age >65 years, obesity, current smoking, white race, and female sex. CONCLUSIONS:In a large, multiethnic, elderly cohort, we found a highly discrepant prevalence of CKD with eGFRcys versus eGFRcr. Determining the optimal method to estimate GFR in elderly populations needs urgent further study to improve risk stratification and drug dosing.Item Open Access Earlier onset and greater severity of disordered mineral metabolism in diabetic patients with chronic kidney disease.(Diabetes care, 2012-05) Wahl, Patricia; Xie, Huiliang; Scialla, Julia; Anderson, Cheryl AM; Bellovich, Keith; Brecklin, Carolyn; Chen, Jing; Feldman, Harold; Gutierrez, Orlando M; Lash, Jim; Leonard, Mary B; Negrea, Lavinia; Rosas, Sylvia E; Anderson, Amanda Hyre; Townsend, Raymond R; Wolf, Myles; Isakova, Tamara; Chronic Renal Insufficiency Cohort Study GroupDisordered mineral metabolism is a common complication of chronic kidney disease (CKD) and a novel risk factor for CKD progression, cardiovascular disease, and mortality. Although diabetes is the leading cause of CKD and is associated with worse clinical outcomes than other etiologies, few studies have evaluated mineral metabolism in CKD according to diabetes status.Using the Chronic Renal Insufficiency Cohort Study, we tested the hypothesis that diabetes is independently associated with lower serum calcium and higher serum phosphate, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23).Compared with participants without diabetes (n = 1,936), those with diabetes (n = 1,820) were more likely to have lower estimated glomerular filtration rate (eGFR), lower serum albumin, and higher urinary protein excretion (all P < 0.001). Unadjusted serum phosphate, PTH, and FGF23 levels were higher and calcium was lower among those with compared with those without diabetes (all P < 0.001). After multivariate adjustment, diabetes remained a significant predictor of serum phosphate, PTH, and FGF23 but not calcium. The eGFR cut point at which 50% of participants met criteria for secondary hyperparathyroidism or elevated FGF23 was higher in participants with diabetes compared with those without (PTH: eGFR 30-39 vs. 20-29, P < 0.001; FGF23: eGFR 50-59 vs. 40-49, P < 0.001).Disordered mineral metabolism begins earlier in the course of CKD and is more severe among CKD patients with compared with those without diabetes. Future studies should explore mechanisms for these differences and whether they contribute to excess risks of adverse clinical outcomes among diabetic patients with CKD.Item Open Access Echocardiography to Screen for Pulmonary Hypertension in CKD(Kidney International Reports, 2020-12-01) Edmonston, Daniel L; Rajagopal, Sudarshan; Wolf, Myles© 2020 International Society of Nephrology Introduction: Pulmonary hypertension (PH) is a common yet incompletely understood complication of chronic kidney disease (CKD). Although transthoracic echocardiogram is commonly used to noninvasively estimate PH, it has not been validated in a CKD population. We investigated the utility of this diagnostic tool for CKD-associated PH in a large right heart catheterization (RHC) cohort. Methods: We reviewed RHC and echocardiography data in 4036 patients (1714 with CKD) obtained between 2011 and 2014 at a single center. We used multivariate regression to determine the associations of echocardiography measurements with PH, and evaluated whether estimated glomerular filtration rate (eGFR) modified these associations. Using internal validation, we sequentially added measurements to predictive models and analyzed the incremental predictive performance using the change in the area under the receiver operating characteristic curve (ΔAUC) and net reclassification improvement. Results: The echocardiography measurements most strongly associated with the diagnosis of PH included tricuspid regurgitant velocity (TRV), tricuspid annular plane systolic excursion (TAPSE), right atrial pressure, diastolic dysfunction, and right ventricular function. Among these measurements, eGFR significantly modified the associations of TAPSE and diastolic dysfunction with the diagnosis of PH. The model consisting of a combination of TRV, right atrial pressure, and TAPSE most accurately predicted the diagnosis of PH in a CKD population (AUC 0.82). Conclusions: The optimal model to predict PH diagnosis included TRV, right atrial pressure, and TAPSE. Since TAPSE more strongly associated with PH in the CKD population, these findings support a CKD-specific approach to the development of noninvasive screening algorithms for PH.Item Open Access FGF23/FGFR4-mediated left ventricular hypertrophy is reversible.(Scientific reports, 2017-05-16) Grabner, Alexander; Schramm, Karla; Silswal, Neerupma; Hendrix, Matt; Yanucil, Christopher; Czaya, Brian; Singh, Saurav; Wolf, Myles; Hermann, Sven; Stypmann, Jörg; Di Marco, Giovana Seno; Brand, Marcus; Wacker, Michael J; Faul, ChristianFibroblast growth factor (FGF) 23 is a phosphaturic hormone that directly targets cardiac myocytes via FGF receptor (FGFR) 4 thereby inducing hypertrophic myocyte growth and the development of left ventricular hypertrophy (LVH) in rodents. Serum FGF23 levels are highly elevated in patients with chronic kidney disease (CKD), and it is likely that FGF23 directly contributes to the high rates of LVH and cardiac death in CKD. It is currently unknown if the cardiac effects of FGF23 are solely pathological, or if they potentially can be reversed. Here, we report that FGF23-induced cardiac hypertrophy is reversible in vitro and in vivo upon removal of the hypertrophic stimulus. Specific blockade of FGFR4 attenuates established LVH in the 5/6 nephrectomy rat model of CKD. Since CKD mimics a form of accelerated cardiovascular aging, we also studied age-related cardiac remodeling. We show that aging mice lacking FGFR4 are protected from LVH. Finally, FGF23 increases cardiac contractility via FGFR4, while known effects of FGF23 on aortic relaxation do not require FGFR4. Taken together, our data highlight a role of FGF23/FGFR4 signaling in the regulation of cardiac remodeling and function, and indicate that pharmacological interference with cardiac FGF23/FGFR4 signaling might protect from CKD- and age-related LVH.Item Unknown Fibroblast growth factor 23 is not associated with and does not induce arterial calcification.(Kidney international, 2013-06) Scialla, Julia J; Lau, Wei Ling; Reilly, Muredach P; Isakova, Tamara; Yang, Hsueh-Ying; Crouthamel, Matthew H; Chavkin, Nicholas W; Rahman, Mahboob; Wahl, Patricia; Amaral, Ansel P; Hamano, Takayuki; Master, Stephen R; Nessel, Lisa; Chai, Boyang; Xie, Dawei; Kallem, Radhakrishna R; Chen, Jing; Lash, James P; Kusek, John W; Budoff, Matthew J; Giachelli, Cecilia M; Wolf, Myles; Chronic Renal Insufficiency Cohort Study InvestigatorsElevated fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease. As a potential mediating mechanism, FGF23 induces left ventricular hypertrophy; however, its role in arterial calcification is less clear. In order to study this, we quantified coronary artery and thoracic aorta calcium by computed tomography in 1501 patients from the Chronic Renal Insufficiency Cohort (CRIC) study within a median of 376 days (interquartile range 331-420 days) of baseline. Baseline plasma FGF23 was not associated with the prevalence or severity of coronary artery calcium after multivariable adjustment. In contrast, higher serum phosphate levels were associated with prevalence and severity of coronary artery calcium, even after adjustment for FGF23. Neither FGF23 nor serum phosphate were consistently associated with thoracic aorta calcium. We could not detect mRNA expression of FGF23 or its coreceptor, klotho, in human or mouse vascular smooth muscle cells, or normal or calcified mouse aorta. Whereas elevated phosphate concentrations induced calcification in vitro, FGF23 had no effect on phosphate uptake or phosphate-induced calcification regardless of phosphate concentration or even in the presence of soluble klotho. Thus, in contrast to serum phosphate, FGF23 is not associated with arterial calcification and does not promote calcification experimentally. Hence, phosphate and FGF23 promote cardiovascular disease through distinct mechanisms.Item Unknown Fibroblast growth factor23 is associated with axonal integrity and neural network architecture in the human frontal lobes.(PloS one, 2018-01) Marebwa, Barbara K; Adams, Robert J; Magwood, Gayenell S; Kindy, Mark; Wilmskoetter, Janina; Wolf, Myles; Bonilha, LeonardoElevated levels of FGF23 in individuals with chronic kidney disease (CKD) are associated with adverse health outcomes, such as increased mortality, large vessel disease, and reduced white matter volume, cardiovascular and cerebrovascular events. Apart from the well-known link between cardiovascular (CV) risk factors, especially diabetes and hypertension, and cerebrovascular damage, elevated FGF23 is also postulated to be associated with cerebrovascular damage independently of CKD. Elevated FGF23 predisposes to vascular calcification and is associated with vascular stiffness and endothelial dysfunction in the general population with normal renal function. These factors may lead to microangiopathic changes in the brain, cumulative ischemia, and eventually to the loss of white matter fibers. The relationship between FGF23 and brain integrity in individuals without CKD has hitherto not been investigated. In this study, we aimed to determine the association between FGF23, and white matter integrity in a cohort of 50 participants with varying degrees of CV risk burden, using high resolution structural human brain connectomes constructed from MRI diffusion images. We observed that increased FGF23 was associated with axonal loss in the frontal lobe, leading to a fragmentation of white matter network organization. This study provides the first description of the relationship between elevated levels of FGF23, white matter integrity, and brain health. We suggest a synergistic interaction of CV risk factors and FGF23 as a potentially novel determinant of brain health.Item Open Access Metabolic Changes with Base-Loading in CKD.(Clinical journal of the American Society of Nephrology : CJASN, 2018-06-22) Scialla, Julia J; Scialla, Julia J; Brown, Landon; Gurley, Susan; Corcoran, David L; Bain, James R; Muehlbauer, Michael J; O'Neal, Sara K; M O'Connell, Thomas; Wolf, Myles; Melamed, Michal L; Hostetter, Thomas H; Abramowitz, Matthew KItem Open Access Modifiers of Plasma 25-hydroxyvitamin D and Chronic Kidney Disease Outcomes in Black Americans: The Jackson Heart Study Supplemental FileLunyera, J; Davenport, Clemontina; Bhavsar, Nrupen; Sims, Mario; Pendergast, Jane; Musani, Solomon; Mwasongwe, Stanford; Wolf, Myles; Diamantidis, Clarissa; Boulware, Ebony; Scialla, JuliaItem Open Access Persistent high serum bicarbonate and the risk of heart failure in patients with chronic kidney disease (CKD): A report from the Chronic Renal Insufficiency Cohort (CRIC) study.(Journal of the American Heart Association, 2015-04-20) Dobre, Mirela; Yang, Wei; Pan, Qiang; Appel, Lawrence; Bellovich, Keith; Chen, Jing; Feldman, Harold; Fischer, Michael J; Ham, LL; Hostetter, Thomas; Jaar, Bernard G; Kallem, Radhakrishna R; Rosas, Sylvia E; Scialla, Julia J; Wolf, Myles; Rahman, Mahboob; CRIC Study InvestigatorsSerum bicarbonate varies over time in chronic kidney disease (CKD) patients, and this variability may portend poor cardiovascular outcomes. The aim of this study was to conduct a time-updated longitudinal analysis to evaluate the association of serum bicarbonate with long-term clinical outcomes: heart failure, atherosclerotic events, renal events (halving of estimated glomerular filtration rate [eGFR] or end-stage renal disease), and mortality.Serum bicarbonate was measured annually, in 3586 participants with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Marginal structural models were created to allow for integration of all available bicarbonate measurements and proper adjustment for time-dependent confounding. During the 6 years follow-up, 512 participants developed congestive heart failure (26/1000 person-years) and 749 developed renal events (37/1000 person-years). The risk of heart failure and death was significantly higher for participants who maintained serum bicarbonate >26 mmol/L for the entire duration of follow-up (hazard ratio [HR] 1.66; 95% confidence interval [CI], 1.23 to 2.23, and HR 1.36, 95% CI 1.02 to 1.82, respectively) compared with participants who kept their bicarbonate 22 to 26 mmol/L, after adjusting for demographics, co-morbidities, medications including diuretics, eGFR, and proteinuria. Participants who maintained serum bicarbonate <22 mmol/L had almost a 2-fold increased risk of renal disease progression (HR 1.97; 95% CI, 1.50 to 2.57) compared with participants with bicarbonate 22 to 26 mmol/L.In this large CKD cohort, persistent serum bicarbonate >26 mmol/L was associated with increased risk of heart failure events and mortality. Further studies are needed to determine the optimal range of serum bicarbonate in CKD to prevent adverse clinical outcomes.Item Open Access Pulmonary Hypertension Subtypes and Mortality in CKD.(American journal of kidney diseases : the official journal of the National Kidney Foundation, 2019-11-12) Edmonston, Daniel L; Parikh, Kishan S; Rajagopal, Sudarshan; Shaw, Linda K; Abraham, Dennis; Grabner, Alexander; Sparks, Matthew A; Wolf, MylesRATIONALE & OBJECTIVE:Pulmonary hypertension (PH) contributes to cardiovascular disease and mortality in patients with chronic kidney disease (CKD), but the pathophysiology is mostly unknown. This study sought to estimate the prevalence and consequences of PH subtypes in the setting of CKD. STUDY DESIGN:Observational retrospective cohort study. SETTING & PARTICIPANTS:We examined 12,618 patients with a right heart catheterization in the Duke Databank for Cardiovascular Disease from January 1, 2000, to December 31, 2014. EXPOSURES:Baseline kidney function stratified by CKD glomerular filtration rate category and PH subtype. OUTCOMES:All-cause mortality. ANALYTICAL APPROACH:Multivariable Cox proportional hazards analysis. RESULTS:In this cohort, 73.4% of patients with CKD had PH, compared with 56.9% of patients without CKD. Isolated postcapillary PH (39.0%) and combined pre- and postcapillary PH (38.3%) were the most common PH subtypes in CKD. Conversely, precapillary PH was the most common subtype in the non-CKD cohort (35.9%). The relationships between mean pulmonary artery pressure, pulmonary capillary wedge pressure, and right atrial pressure with mortality were similar in both the CKD and non-CKD cohorts. Compared with those without PH, precapillary PH conferred the highest mortality risk among patients without CKD (HR, 2.27; 95% CI, 2.00-2.57). By contrast, in those with CKD, combined pre- and postcapillary PH was associated with the highest risk for mortality in CKD in adjusted analyses (compared with no PH, HRs of 1.89 [95% CI, 1.57-2.28], 1.87 [95% CI, 1.52-2.31], 2.13 [95% CI, 1.52-2.97], and 1.63 [95% CI, 1.12-2.36] for glomerular filtration rate categories G3a, G3b, G4, and G5/G5D). LIMITATIONS:The cohort referred for right heart catheterization may not be generalizable to the general population. Serum creatinine data in the 6 months preceding catheterization may not reflect true baseline CKD. Observational design precludes assumptions of causality. CONCLUSIONS:In patients with CKD referred for right heart catheterization, PH is common and associated with poor survival. Combined pre- and postcapillary PH was common and portended the worst survival for patients with CKD.Item Open Access Risk Factors for Heart Failure in Patients With Chronic Kidney Disease: The CRIC (Chronic Renal Insufficiency Cohort) Study.(Journal of the American Heart Association, 2017-05-17) He, Jiang; Shlipak, Michael; Anderson, Amanda; Roy, Jason A; Feldman, Harold I; Kallem, Radhakrishna Reddy; Kanthety, Radhika; Kusek, John W; Ojo, Akinlolu; Rahman, Mahboob; Ricardo, Ana C; Soliman, Elsayed Z; Wolf, Myles; Zhang, Xiaoming; Raj, Dominic; Hamm, Lee; CRIC (Chronic Renal Insufficiency Cohort) InvestigatorsBACKGROUND:Heart failure is common in patients with chronic kidney disease. We studied risk factors for incident heart failure among 3557 participants in the CRIC (Chronic Renal Insufficiency Cohort) Study. METHODS AND RESULTS:Kidney function was assessed by estimated glomerular filtration rate (eGFR) using serum creatinine, cystatin C, or both, and 24-hour urine albumin excretion. During an average of 6.3 years of follow-up, 452 participants developed incident heart failure. After adjustment for age, sex, race, and clinical site, hazard ratio (95% CI) for heart failure associated with 1 SD lower creatinine-based eGFR was 1.67 (1.49, 1.89), 1 SD lower cystatin C-based-eGFR was 2.43 (2.10, 2.80), and 1 SD higher log-albuminuria was 1.65 (1.53, 1.78), all P<0.001. When all 3 kidney function measures were simultaneously included in the model, lower cystatin C-based eGFR and higher log-albuminuria remained significantly and directly associated with incidence of heart failure. After adjusting for eGFR, albuminuria, and other traditional cardiovascular risk factors, anemia (1.37, 95% CI 1.09, 1.72, P=0.006), insulin resistance (1.16, 95% CI 1.04, 1.28, P=0.006), hemoglobin A1c (1.27, 95% CI 1.14, 1.41, P<0.001), interleukin-6 (1.15, 95% CI 1.05, 1.25, P=0.002), and tumor necrosis factor-α (1.10, 95% CI 1.00, 1.21, P=0.05) were all significantly and directly associated with incidence of heart failure. CONCLUSIONS:Our study indicates that cystatin C-based eGFR and albuminuria are better predictors for risk of heart failure compared to creatinine-based eGFR. Furthermore, anemia, insulin resistance, inflammation, and poor glycemic control are independent risk factors for the development of heart failure among patients with chronic kidney disease.