41 results on '"Dubin, Ruth F."'
Search Results
2. FGF23 and Cause‐Specific Mortality in Community‐Living Individuals—The Health, Aging, and Body Composition Study
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Sharma, Shilpa, Katz, Ronit, Dubin, Ruth F, Drew, David A, Gutierrez, Orlando M, Shlipak, Michael G, Sarnak, Mark J, and Ix, Joachim H
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Aging ,2.1 Biological and endogenous factors ,Aetiology ,Generic health relevance ,Good Health and Well Being ,Aged ,Biomarkers ,Cardiovascular Diseases ,Cause of Death ,Female ,Fibroblast Growth Factor-23 ,Fibroblast Growth Factors ,Humans ,Independent Living ,Male ,Prospective Studies ,FGF23 ,assays ,mortality ,cause‐ ,specific ,cause-specific ,Medical and Health Sciences ,Geriatrics - Abstract
ObjectivesFibroblast growth factor (FGF)-23 is a key regulator of mineral metabolism and has been linked with left ventricular hypertrophy in animal models. Most existing epidemiologic studies evaluated a C-terminal FGF23 assay which measures both the intact (active) hormone and inactive fragments. The relationship of intact FGF23 with cause-specific mortality is unknown.DesignProspective analyses of data from Health, Aging, & Body Composition (HABC) study.SettingCommunity-living adults aged 70 to 79 years with longitudinal follow up.
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- 2021
3. Identification of Novel Biomarkers and Pathways for Coronary Artery Calcification in Nondiabetic Patients on Hemodialysis Using Metabolomic Profiling.
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Chen, Wei, Fitzpatrick, Jessica, Sozio, Stephen M, Jaar, Bernard G, Estrella, Michelle M, Riascos-Bernal, Dario F, Wu, Tong Tong, Qiu, Yunping, Kurland, Irwin J, Dubin, Ruth F, Chen, Yabing, Parekh, Rulan S, Bushinsky, David A, and Sibinga, Nicholas ES
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Humans ,Renal Dialysis ,Case-Control Studies ,Coronary Artery Disease ,Metabolomics ,Vascular Calcification ,Biomarkers ,Diabetes ,Clinical Research ,Heart Disease - Coronary Heart Disease ,Heart Disease ,Prevention ,Cardiovascular ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,mineral metabolism ,arginine and proline metabolism ,arterial calcification ,bile acid ,coronary artery disease ,dialysis ,metabolomics - Abstract
BackgroundA better understanding of the pathophysiology involving coronary artery calcification (CAC) in patients on hemodialysis (HD) will help to develop new therapies. We sought to identify the differences in metabolomics profiles between patients on HD with and without CAC.MethodsIn this case-control study, nested within a cohort of 568 incident patients on HD, the cases were patients without diabetes with a CAC score >100 (n=51), and controls were patients without diabetes with a CAC score of zero (n=48). We measured 452 serum metabolites in each participant. Metabolites and pathway scores were compared using Mann-Whitney U tests, partial least squares-discriminant analyses, and pathway enrichment analyses.ResultsCompared with controls, cases were older (64±13 versus 42±12 years) and were less likely to be Black (51% versus 94%). We identified three metabolites in bile-acid synthesis (chenodeoxycholic, deoxycholic, and glycolithocholic acids) and one pathway (arginine/proline metabolism). After adjusting for demographics, higher levels of chenodeoxycholic, deoxycholic, and glycolithocholic acids were associated with higher odds of having CAC; comparing the third with the first tertile of each bile acid, the OR was 6.34 (95% CI, 1.12 to 36.06), 6.73 (95% CI, 1.20 to 37.82), and 8.53 (95% CI, 1.50 to 48.49), respectively. These associations were no longer significant after further adjustment for coronary artery disease and medication use. Per 1 unit higher in the first principal component score, arginine/proline metabolism was associated with CAC after adjusting for demographics (OR, 1.83; 95% CI, 1.06 to 3.15), and the association remained significant with additional adjustments for statin use (OR, 1.84; 95% CI, 1.04 to 3.27).ConclusionsAmong patients on HD without diabetes mellitus, chenodeoxycholic, deoxycholic, and glycolithocholic acids may be potential biomarkers for CAC, and arginine/proline metabolism is a plausible mechanism to study for CAC. These findings need to be confirmed in future studies.
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- 2021
4. Alterations in the Circulating Proteome Associated with Albuminuria
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Kiernan, Elizabeth, Surapaneni, Aditya, Zhou, Linda, Schlosser, Pascal, Walker, Keenan A., Rhee, Eugene P., Ballantyne, Christie M., Deo, Rajat, Dubin, Ruth F., Ganz, Peter, Coresh, Josef, and Grams, Morgan E.
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- 2023
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5. Incident heart failure in chronic kidney disease: proteomics informs biology and risk stratification.
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Dubin, Ruth F, Deo, Rajat, Ren, Yue, Wang, Jianqiao, Pico, Alexander R, Mychaleckyj, Josyf C, Kozlitina, Julia, Arthur, Victoria, Lee, Hongzhe, Shah, Amil, Feldman, Harold, Bansal, Nisha, Zelnick, Leila, Rao, Panduranga, Sukul, Nidhi, Raj, Dominic S, Mehta, Rupal, Rosas, Sylvia E, Bhat, Zeenat, and Weir, Matthew R
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BRAIN natriuretic factor ,CHRONIC kidney failure ,DISEASE risk factors ,HEART failure ,GLOMERULAR filtration rate - Abstract
Background and Aims Incident heart failure (HF) among individuals with chronic kidney disease (CKD) incurs hospitalizations that burden patients and health care systems. There are few preventative therapies, and the Pooled Cohort equations to Prevent Heart Failure (PCP-HF) perform poorly in the setting of CKD. New drug targets and better risk stratification are urgently needed. Methods In this analysis of incident HF, SomaScan V4.0 (4638 proteins) was analysed in 2906 participants of the Chronic Renal Insufficiency Cohort (CRIC) with validation in the Atherosclerosis Risk in Communities (ARIC) study. The primary outcome was 14-year incident HF (390 events); secondary outcomes included 4-year HF (183 events), HF with reduced ejection fraction (137 events), and HF with preserved ejection fraction (165 events). Mendelian randomization and Gene Ontology were applied to examine causality and pathways. The performance of novel multi-protein risk models was compared to the PCP-HF risk score. Results Over 200 proteins were associated with incident HF after adjustment for estimated glomerular filtration rate at P < 1 × 10
−5 . After adjustment for covariates including N-terminal pro-B-type natriuretic peptide, 17 proteins remained associated at P < 1 × 10−5 . Mendelian randomization associations were found for six proteins, of which four are druggable targets: FCG2B, IGFBP3, CAH6, and ASGR1. For the primary outcome, the C -statistic (95% confidence interval [CI]) for the 48-protein model in CRIC was 0.790 (0.735, 0.844) vs. 0.703 (0.644, 0.762) for the PCP-HF model (P =.001). C -statistic (95% CI) for the protein model in ARIC was 0.747 (0.707, 0.787). Conclusions Large-scale proteomics reveal novel circulating protein biomarkers and potential mediators of HF in CKD. Proteomic risk models improve upon the PCP-HF risk score in this population. [ABSTRACT FROM AUTHOR]- Published
- 2024
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6. Urinary Tubular Injury Biomarkers Are Associated With ESRD and Death in the REGARDS Study.
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Dubin, Ruth F, Judd, Suzanne, Scherzer, Rebecca, Shlipak, Michael, Warnock, David G, Cushman, Mary, Sarnak, Mark, Parikh, Chirag, Bennett, Michael, Powe, Neil, and Peralta, Carmen A
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chronic kidney disease ,end-stage renal disease ,tubular injury ,urinary KIM-1 ,urinary NGAL - Abstract
IntroductionUrinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary kidney injury molecule-1 (uKIM-1) are established markers of subclinical acute kidney injury. In persons with reduced estimated glomerular filtration rate (eGFR) and albuminuria who are at high risk for end-stage renal disease (ESRD) and death, the associations of these urinary markers with incident ESRD or death is an area of active investigation.MethodsAmong 1472 black and white participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study with eGFR ≤60 ml/min per 1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] cystatin, 2012) and albumin-to-creatinine ratio (ACR) ≥30 mg/g, we evaluated the associations of baseline uNGAL and uKIM-1 with progression to ESRD and all-cause death. Cox models were sequentially adjusted for urinary creatinine, traditional risk factors, C-reactive protein, ACR, and eGFR.ResultsThere were 257 ESRD events and 819 deaths over a median follow-up of 5.7 and 6.5 years, respectively. In demographic adjusted models, higher levels of uNGAL were associated with increased risk of ESRD and death, but these associations were attenuated in fully adjusted models including baseline eGFR for both ESRD (hazard ratio [HR] = 1.06 per doubling, 95% confidence interval [CI] 0.98-1.14) and death (HR = 1.04, 95% CI = 1.00-1.08). Higher levels of uKIM-1 were associated with increased risk of ESRD and death in demographic-adjusted models, and although attenuated in fully adjusted models, remained statistically significant for both ESRD (HR = 1.24 per doubling, 95% CI = 1.08-1.42) and death (HR = 1.10, 95% CI =1.03-1.19).ConclusionIn this cohort of high-risk patients with baseline eGFR ≤60 ml/min per 1.73 m2 and albuminuria, renal tubular injury is associated with higher mortality and progression to ESRD. Further studies are necessary to investigate the mechanism underlying this increased risk.
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- 2018
7. Proteomic analysis of heart failure hospitalization among patients with chronic kidney disease: The Heart and Soul Study
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Dubin, Ruth F, Whooley, Mary, Pico, Alexander, Ganz, Peter, Schiller, Nelson B, and Meyer, Craig
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Biomedical and Clinical Sciences ,Clinical Sciences ,Cardiovascular ,Heart Disease ,Kidney Disease ,Clinical Research ,Renal and urogenital ,Aged ,Aged ,80 and over ,Angiopoietin-2 ,Biomarkers ,Extracellular Matrix Proteins ,Female ,Glomerular Filtration Rate ,Heart Failure ,Hospitalization ,Humans ,Male ,Middle Aged ,Prognosis ,Proteomics ,Receptor ,Notch1 ,Renal Insufficiency ,Chronic ,Risk Assessment ,Tartrate-Resistant Acid Phosphatase ,General Science & Technology - Abstract
BackgroundPatients with chronic kidney disease (CKD) are at increased risk for heart failure (HF). We aimed to investigate differences in proteins associated with HF hospitalizations among patients with and without CKD in the Heart and Soul Study.Methods and resultsWe measured 1068 unique plasma proteins from baseline samples of 974 participants in The Heart and Soul Study who were followed for HF hospitalization over a median of 7 years. We sequentially applied forest regression and Cox survival analyses to select prognostic proteins. Among participants with CKD, four proteins were associated with HF at Bonferroni-level significance (p
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- 2018
8. Renal Dysfunction in Heart Failure With Preserved Ejection Fraction: Insights From the RELAX Trial
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Patel, RAVI B., MEHTA, RUPAL, REDFIELD, MARGARET M., BORLAUG, BARRY A., HERNANDEZ, ADRIAN F., SHAH, SANJIV J., and DUBIN, RUTH F.
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- 2020
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9. Associations of Macro- and Microvascular Endothelial Dysfunction With Subclinical Ventricular Dysfunction in End-Stage Renal Disease
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Dubin, Ruth F, Guajardo, Isabella, Ayer, Amrita, Mills, Claire, Donovan, Catherine, Beussink, Lauren, Scherzer, Rebecca, Ganz, Peter, and Shah, Sanjiv J
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Clinical Research ,Kidney Disease ,Heart Disease ,Cardiovascular ,Good Health and Well Being ,Academic Medical Centers ,Adult ,Aged ,Analysis of Variance ,Blood Pressure Determination ,Brachial Artery ,California ,Capillary Permeability ,Cohort Studies ,Cross-Sectional Studies ,Disease Progression ,Echocardiography ,Doppler ,Endothelium ,Vascular ,Female ,Heart Failure ,Humans ,Kidney Failure ,Chronic ,Linear Models ,Male ,Middle Aged ,Multivariate Analysis ,Peritoneal Dialysis ,Prospective Studies ,Renal Dialysis ,Risk Assessment ,Severity of Illness Index ,Ventricular Dysfunction ,Left ,cardiovascular disease ,echocardiography ,heart failure ,Cardiorespiratory Medicine and Haematology ,Public Health and Health Services ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
Patients with end-stage renal disease (ESRD) suffer high rates of heart failure and cardiovascular mortality, and we lack a thorough understanding of what, if any, modifiable factors contribute to cardiac dysfunction in these high-risk patients. To evaluate endothelial function as a potentially modifiable cause of cardiac dysfunction in ESRD, we investigated cross-sectional associations of macro- and microvascular dysfunction with left and right ventricular dysfunction in a well-controlled ESRD cohort. We performed comprehensive echocardiography, including tissue Doppler imaging and speckle-tracking echocardiography of the left and right ventricle, in 149 ESRD patients enrolled in an ongoing prospective, observational study. Of these participants, 123 also underwent endothelium-dependent flow-mediated dilation of the brachial artery (macrovascular function). Microvascular function was measured as the velocity time integral of hyperemic blood flow after cuff deflation. Impaired flow-mediated dilation was associated with higher left ventricular mass, independently of age and blood pressure: per 2-fold lower flow-mediated dilation, left ventricular mass was 4.1% higher (95% confidence interval, 0.49-7.7; P=0.03). After adjustment for demographics, blood pressure, comorbidities, and medications, a 2-fold lower velocity time integral was associated with 9.5% higher E/e' ratio (95% confidence interval, 1.0-16; P=0.03) and 6.7% lower absolute right ventricular longitudinal strain (95% confidence interval, 2.0-12; P=0.003). Endothelial dysfunction is a major correlate of cardiac dysfunction in ESRD, particularly diastolic and right ventricular dysfunction, in patients whose volume status is well controlled. Future investigations are needed to determine whether therapies targeting the vascular endothelium could improve cardiac outcomes in ESRD.
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- 2016
10. Associations of Tissue Doppler Imaging with NT‐proBNP and hs‐TnT: A Pilot Study in End‐Stage Renal Disease
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Dubin, Ruth F, Beatty, Alexis L, Teerlink, John R, Schiller, Nelson B, Alokozai, Dean, and Johansen, Kirsten L
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Biomedical and Clinical Sciences ,Clinical Sciences ,Kidney Disease ,Clinical Research ,Cardiovascular ,Aged ,Biomarkers ,Cohort Studies ,Echocardiography ,Doppler ,Female ,Follow-Up Studies ,Humans ,Kidney Failure ,Chronic ,Male ,Middle Aged ,Multivariate Analysis ,Natriuretic Peptide ,Brain ,Peptide Fragments ,Pilot Projects ,Regression Analysis ,Renal Dialysis ,Sensitivity and Specificity ,Treatment Outcome ,Troponin T ,Ventricular Dysfunction ,Left ,Doppler tissue imaging ,end-stage renal disease ,End-stage renal disease ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
BackgroundDiastolic dysfunction is common and associated with higher mortality in the end-stage renal disease (ESRD) population. E/E', a measure derived from tissue Doppler imaging (TDI), is a correlate of left ventricular (LV) filling pressures. E/E' may be viewed as a confirmatory marker of diastolic dysfunction, but it is not routinely used to quantify diastolic dysfunction. Whether E/E' is associated with N-terminal brain natriuretic peptide (NT-proBNP) or high sensitivity troponin T (hs-TnT) in this population is not known.MethodsWe performed echocardiograms and serology prior to the 2nd or 3rd dialysis session of the week on 35 chronic hemodialysis patients. We compared TDI parameters (E/E' and E' alone), traditional categories of diastolic function (normal, impaired, pseudonormal or restrictive), and ejection fraction (EF) as potential predictors of the outcomes NT-proBNP and hs-TnT.ResultsHigher E/E' was associated with higher NT-proBNP (rho 0.48, P = 0.004) and hs-TnT (rho 0.37, P = 0.03). EF did not have statistically significant associations with NT-proBNP (rho -0.2, P = 0.4) or hs-TnT (rho -0.24, P = 0.16). As compared to patients with normal diastolic function, those with impaired or pseudonormal filling patterns did not have significantly different levels of NT-proBNP (P = 0.46); patients in traditional categories of worsened diastolic function actually had lower hs-TnT (P = 0.02). The associations of E/E' with higher NT-proBNP and hs-TnT persisted after multivariate adjustment for EF, LV mass, and volume status.ConclusionsTissue Doppler imaging may be more useful in evaluating cardiac function than traditional measures of diastolic dysfunction in the ESRD population.
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- 2014
11. Determinants of hemodialysis‐induced segmental wall motion abnormalities
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Dubin, Ruth F, Beatty, Alexis L, Teerlink, John R, Schiller, Nelson B, Bolger, Ann F, Alokozai, Dean, Peralta, Carmen A, and Johansen, Kirsten L
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Research ,Bioengineering ,Cardiovascular ,Heart Disease ,Heart Disease - Coronary Heart Disease ,Assistive Technology ,Kidney Disease ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Cohort Studies ,Coronary Artery Disease ,Echocardiography ,Female ,Heart Failure ,Hemodynamics ,Humans ,Kidney Failure ,Chronic ,Male ,Middle Aged ,Renal Dialysis ,Risk Factors ,Stroke Volume ,Ventricular Dysfunction ,Left ,Heart failure ,hemodialysis ,end-stage renal disease ,Clinical Sciences ,Urology & Nephrology ,Clinical sciences - Abstract
Patients who demonstrate worsening of cardiac wall motion (WM) during hemodialysis have higher 1-year mortality. We sought to identify risk factors for dialysis-induced WM abnormalities. Additionally, we examined the effects of hemodialysis on other parameters of cardiac function. Forty patients underwent echocardiography directly before dialysis and during the last hour of dialysis (79 dialysis sessions). Candidate predictors for intradialytic worsening of WM included age, a history of heart failure (HF) or coronary artery disease, changes in blood pressure or heart rate, high sensitivity cardiac troponin T and N-terminal brain natriuretic peptide. Among 40 patients, WM worsened segmentally in eight patients (20%), worsened globally in one patient (3%), and improved segmentally in four patients (10%). Diastolic function worsened in 44% of patients, and left ventricular ejection fraction was largely unchanged during dialysis. The case of globally worsened WM occurred in the setting of intradialytic hypertension in a patient without HF. Surprisingly, history of coronary artery disease, hemodynamics, and serologic factors were not associated with worsened segmental WM during dialysis. After adjustment for history of coronary artery disease and other cardiac risk factors, patients with a history of HF had a threefold higher risk of worsening segmental WM during dialysis (RR 3.1, 95% CI [1.1, 9], p = 0.04). In conclusion, patients with a history of clinical HF were at higher risk of intradialytic worsening of segmental WM. Further studies are needed to determine the mechanism of this association and whether cardioprotective medications could ameliorate this adverse cardiac effect of hemodialysis.
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- 2014
12. Predictors of high sensitivity cardiac troponin T in chronic kidney disease patients: a cross-sectional study in the chronic renal insufficiency cohort (CRIC)
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Dubin, Ruth F, Li, Yongmei, He, Jiang, Jaar, Bernard G, Kallem, Radhakrishna, Lash, James P, Makos, Gail, Rosas, Sylvia E, Soliman, Elsayed Z, Townsend, Ray R, Yang, Wei, Go, Alan S, Keane, Martin, deFilippi, Christopher, Mishra, Rakesh, Wolf, Myles, and Shlipak, Michael G
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Abstract Background Cardiac troponin T is independently associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). Serum levels of high sensitivity cardiac troponin T (hs-TnT) reflect subclinical myocardial injury in ambulatory patients. We sought to determine the distribution and predictors of hs-TnT in CKD patients without overt cardiovascular disease (CVD). Methods We studied 2464 participants within the multi-ethnic Chronic Renal Insufficiency Cohort (CRIC) who did not have self-reported CVD. We considered renal and non-renal factors as potential determinants of hs-TnT, including demographics, comorbidities, left ventricular (LV) mass, serologic factors, estimated glomerular filtration rate (eGFR) and albumin to creatinine ratio. Results Hs-TnT was detectable in 81% of subjects, and the median (IQR) hs-TnT was 9.4 pg/ml (4.3-18.3). Analysis was performed using Tobit regression, adjusting for renal and non-renal factors. After adjustment, lower eGFR was associated with higher expected hs-TnT; participants with eGFR 60. Older age, male gender, black race, LV mass, diabetes and higher blood pressure all had strong, independent associations with higher expected hs-TnT. Conclusions Knowledge of the determinants of hs-TnT in this cohort may guide further research on the pathology of heart disease in patients with CKD and help to stratify sub-groups of CKD patients at higher cardiovascular risk.
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- 2013
13. Association of segmental wall motion abnormalities occurring during hemodialysis with post-dialysis fatigue
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Dubin, Ruth F, Teerlink, John R, Schiller, Nelson B, Alokozai, Dean, Peralta, Carmen A, and Johansen, Kirsten L
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Biomedical and Clinical Sciences ,Clinical Sciences ,Cardiovascular ,Bioengineering ,Clinical Research ,Kidney Disease ,Anemia ,Cross-Sectional Studies ,Echocardiography ,Fatigue ,Female ,Follow-Up Studies ,Hemodynamics ,Humans ,Kidney Diseases ,Male ,Middle Aged ,Movement ,Nonlinear Dynamics ,Prognosis ,Renal Dialysis ,Ventricular Dysfunction ,Left ,end-stage renal disease ,hemodialysis ,post-dialysis fatigue ,Urology & Nephrology ,Clinical sciences - Abstract
BackgroundPost-dialysis fatigue (PDF) is a common, debilitating symptom that remains poorly understood. Cardiac wall motion abnormalities (WMAs) may worsen during dialysis, but it is unknown whether WMA are associated with PDF.MethodsForty patients were recruited from University of California San Francisco-affiliated dialysis units between January 2010 and February 2011. Participants underwent echocardiograms before and during the last hour of 79 dialysis sessions. Myocardial segments were graded 1-4 by a blinded reviewer, with four representing the worst WMA, and the segmental scores were summed for each echocardiogram. Patients completed questionnaires about their symptoms. Severe PDF (defined as lasting >2 h after dialysis) was analysed using a generalized linear model with candidate predictors including anemia, intradialytic hemodynamics and cardiac function.ResultsForty-four percent of patients with worsened WMA (n=9) had severe PDF, compared with 13% of patients with improved or unchanged WMA (P = 0.04). A one-point increase in the WMA score during dialysis was associated with a 10% higher RR of severe PDF [RR: 1.1, 95% CI (1.1, 1.2), P < 0.001]. After multivariable adjustment, every point increase in the WMA score was associated with a 2-fold higher risk of severe PDF [RR: 1.9, 95% CI (1.4, 2.6), P < 0.001]. History of depression was associated with severe PDF after adjustment for demographics and comorbidities [RR: 3.4, 95% CI (1.3, 9), P = 0.01], but anemia, hemodynamics and other parameters of cardiac function were not.ConclusionsAlthough cross-sectional, these results suggest that some patients may experience severe PDF as a symptom of cardiac ischemia occurring during dialysis.
- Published
- 2013
14. Evaluation of a large-scale aptamer proteomics platform among patients with kidney failure on dialysis.
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Ren, Yue, Ruan, Peifeng, Segal, Mark, Dobre, Mirela, Schelling, Jeffrey R., Banerjee, Upasana, Shafi, Tariq, Ganz, Peter, and Dubin, Ruth F.
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KIDNEY failure ,HEMODIALYSIS ,CHRONIC kidney failure ,APTAMERS ,BLOOD proteins - Abstract
Background: Patients with kidney failure suffer high mortality, and we currently lack markers for risk stratification for these patients. We carried out a quality control study of a modified aptamer assay (SomaScan v.4.0) that measures ~ 5000 proteins, in preparation for a larger study using this platform in cohorts with kidney failure. Methods: Forty participants from the Cardiac, Endothelial Function and Arterial Stiffness in End-Stage Renal Disease (CERES study) were selected to analyze technical and short-term biological variability, orthogonal correlations and differential protein expression in plasma from patients who died during 2.5 year follow-up. Long-term (one year) variability was studied in 421 participants in the Chronic Renal Insufficiency Cohort. We evaluated 4849 aptamers (4607 unique proteins) using data formats including raw data and data formatted using Adaptive Normalization by Maximum Likelihood (ANML), an algorithm developed for SomaScan data in individuals with normal kidney function. Results: In ANML format, median[IQR] intra-assay coefficient of variation (CV) was 2.38%[1.76, 3.40] and inter-assay CV was 7.38%[4.61, 13.12]. Short-term within-subject CV was 5.76% [3.35, 9.72]; long-term CV was 8.71%[5.91, 13.37]. Spearman correlations between aptamer and traditional assays for PTH, NT-proBNP, FGF-23 and CRP were all > 0.7. Fold-change (FC) in protein levels among non-survivors, significant after Bonferroni correction, included SVEP1 (FC[95% CI] 2.14 [1.62, 2.82]), keratocan (1.74 [1.40, 2.15]) and LanC-like protein 1 (0.56 [0.45, 0.70]). Compared to raw aptamer data, technical and short-term biological variability in paired samples was lower in ANML-formatted data. ANML formatting had minimal impact on orthogonal correlations with traditional assays or the associations of proteins with the phenotype of mortality. Conclusions: SomaScan had excellent technical variability and low within-subject short-term variability. ANML formatting could facilitate comparison of biomarker results with other studies that utilize this format. We expect SomaScan to provide novel and reproducible information in patients with kidney failure on dialysis. [ABSTRACT FROM AUTHOR]
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- 2023
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15. Proteomic cardiovascular risk assessment in chronic kidney disease
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Deo, Rajat, primary, Dubin, Ruth F, additional, Ren, Yue, additional, Murthy, Ashwin C, additional, Wang, Jianqiao, additional, Zheng, Haotian, additional, Zheng, Zihe, additional, Feldman, Harold, additional, Shou, Haochang, additional, Coresh, Josef, additional, Grams, Morgan, additional, Surapaneni, Aditya L, additional, Bhat, Zeenat, additional, Cohen, Jordana B, additional, Rahman, Mahboob, additional, He, Jiang, additional, Saraf, Santosh L, additional, Go, Alan S, additional, Kimmel, Paul L, additional, Vasan, Ramachandran S, additional, Segal, Mark R, additional, Li, Hongzhe, additional, and Ganz, Peter, additional
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- 2023
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16. Analytical and Biological Variability of a Commercial Modified Aptamer Assay in Plasma Samples of Patients with Chronic Kidney Disease
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Dubin, Ruth F, primary, Deo, Rajat, additional, Ren, Yue, additional, Lee, Hongzhe, additional, Shou, Haochang, additional, Feldman, Harold, additional, Kimmel, Paul, additional, Waikar, Sushrut S, additional, Rhee, Eugene P, additional, Tin, Adrienne, additional, Chen, Jingsha, additional, Coresh, Joseph, additional, Go, Alan S, additional, Kelly, Tanika, additional, Rao, Paduranga S, additional, Chen, Teresa K, additional, Segal, Mark R, additional, and Ganz, Peter, additional
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- 2023
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17. Soluble Guanylate Cyclase Stimulators: a Novel Treatment Option for Heart Failure Associated with Cardiorenal Syndromes?
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Dubin, Ruth F. and Shah, Sanjiv J.
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- 2016
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18. Left atrial strain is associated with adverse cardiovascular events in patients with end‐stage renal disease: Findings from the Cardiac, Endothelial Function and Arterial Stiffness in ESRD ( CERES ) study
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Ayer, Amrita, primary, Banerjee, Upasana, additional, Mills, Claire, additional, Donovan, Catherine, additional, Nelson, Lauren, additional, Shah, Sanjiv J., additional, and Dubin, Ruth F., additional
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- 2022
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19. Association of chronic kidney disease with abnormal cardiac mechanics and adverse outcomes in patients with heart failure and preserved ejection fraction
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Unger, Erin D., Dubin, Ruth F., Deo, Rajat, Daruwalla, Vistasp, Friedman, Julie L., Medina, Crystal, Beussink, Lauren, Freed, Benjamin H., and Shah, Sanjiv J.
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- 2016
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20. Proteins Associated with Risk of Kidney Function Decline in the General Population
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Grams, Morgan E., primary, Surapaneni, Aditya, additional, Chen, Jingsha, additional, Zhou, Linda, additional, Yu, Zhi, additional, Dutta, Diptavo, additional, Welling, Paul A., additional, Chatterjee, Nilanjan, additional, Zhang, Jingning, additional, Arking, Dan E., additional, Chen, Teresa K., additional, Rebholz, Casey M., additional, Yu, Bing, additional, Schlosser, Pascal, additional, Rhee, Eugene P., additional, Ballantyne, Christie M., additional, Boerwinkle, Eric, additional, Lutsey, Pamela L., additional, Mosley, Thomas, additional, Feldman, Harold I., additional, Dubin, Ruth F., additional, Ganz, Peter, additional, Lee, Hongzhe, additional, Zheng, Zihe, additional, and Coresh, Josef, additional
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- 2021
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21. Testican-2 Is Associated with Reduced Risk of Incident ESKD
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Wen, Donghai, Zhou, Linda, Zheng, Zihe, Surapaneni, Aditya, Ballantyne, Christie M., Hoogeveen, Ron C., Shlipak, Michael G., Waikar, Sushrut S., Vasan, Ramachandran S., Kimmel, Paul L., Dubin, Ruth F., Deo, Rajat, Feldman, Harold I., Ganz, Peter, Coresh, Josef, Grams, Morgan E., and Rhee, Eugene P.
- Abstract
Standard blood markers of kidney function undergo renal clearance and are thus inversely correlated with estimated glomerular filtration rate (eGFR). Recent work has shown that blood levels of the podocyte-derived protein testican-2 are positively correlated with eGFR among individuals with relatively normal kidney function. The current study considers blood testican-2 levels among three cohorts of >8,000 individuals in total, including many with established kidney disease. Testican-2 levels are positively correlated with eGFR across the full range of kidney health, with higher levels associated with lower risk of incident end stage kidney disease (ESKD), even after adjusting for baseline eGFR, proteinuria, and other kidney disease risk factors. This study highlights a positive association between testican-2 and kidney health and prognosis.
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- 2023
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22. Left atrial strain is associated with adverse cardiovascular events in patients with end-stage renal disease: Findings from the Cardiac, Endothelial Function and Arterial Stiffness in ESRD (CERES) study.
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Ayer, Amrita, Banerjee, Upasana, Mills, Claire, Donovan, Catherine, Nelson, Lauren, Shah, Sanjiv J., and Dubin, Ruth F.
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- 2022
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23. FGF23 and Cause‐Specific Mortality in Community‐Living Individuals—The Health, Aging, and Body Composition Study
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Sharma, Shilpa, primary, Katz, Ronit, additional, Dubin, Ruth F., additional, Drew, David A., additional, Gutierrez, Orlando M., additional, Shlipak, Michael G., additional, Sarnak, Mark J., additional, and Ix, Joachim H., additional
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- 2020
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24. Proteomics for personalized cardiovascular risk assessment: in pursuit of the Holy Grail
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Ganz, Peter, primary, Deo, Rajat, additional, and Dubin, Ruth F, additional
- Published
- 2020
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25. Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies conference
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House, Andrew A., Wanner, Christoph, Sarnak, Mark J., Piña, Ileana L., McIntyre, Christopher W., Komenda, Paul, Kasiske, Bertram L., Deswal, Anita, deFilippi, Christopher R., Cleland, John G.F., Anker, Stefan D., Herzog, Charles A., Cheung, Michael, Wheeler, David C., Winkelmayer, Wolfgang C., McCullough, Peter A., Abu-Alfa, Ali K., Amann, Kerstin, Aonuma, Kazutaka, Appel, Lawrence J., Baigent, Colin, Bakris, George L., Banerjee, Debasish, Boletis, John N., Bozkurt, Biykem, Butler, Javed, Chan, Christopher T., Costanzo, Maria Rosa, Dubin, Ruth F., Filippatos, Gerasimos, Gikonyo, Betty M., Gikonyo, Dan K., Hajjar, Roger J., Iseki, Kunitoshi, Ishii, Hideki, Knoll, Greg A., Lenihan, Colin R., Lentine, Krista L., Lerma, Edgar V., Macedo, Etienne, Mark, Patrick B., Noiri, Eisei, Palazzuoli, Alberto, Pecoits-Filho, Roberto, Pitt, Bertram, Rigatto, Claudio, Rossignol, Patrick, Setoguchi, Soko, Sood, Manish M., Störk, Stefan, Suri, Rita S., Szummer, Karolina, Tang, Sydney C.W., Tangri, Navdeep, Thompson, Aliza, Vijayaraghavan, Krishnaswami, Walsh, Michael, Wang, Angela Yee-Moon, and Weir, Matthew R.
- Subjects
urologic and male genital diseases ,R1 ,female genital diseases and pregnancy complications - Abstract
The incidence and prevalence of heart failure (HF) and chronic kidney disease (CKD) are increasing, and as such a better understanding of the interface between both conditions is imperative for developing optimal strategies for their detection, prevention, diagnosis, and management. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international, multidisciplinary Controversies Conference titled Heart Failure in CKD. Breakout group discussions included (i) HF with preserved ejection fraction (HFpEF) and nondialysis CKD, (ii) HF with reduced ejection fraction (HFrEF) and nondialysis CKD, (iii) HFpEF and dialysis-dependent CKD, (iv) HFrEF and dialysis-dependent CKD, and (v) HF in kidney transplant patients. The questions that formed the basis of discussions are available on the KDIGO website http://kdigo.org/conferences/heart-failure-in-ckd/, and the deliberations from the conference are summarized here.
- Published
- 2019
26. Proteomics and Metabolomics in Kidney Disease, including Insights into Etiology, Treatment, and Prevention
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Dubin, Ruth F., primary and Rhee, Eugene P., additional
- Published
- 2019
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27. Associations of microvascular dysfunction with cardiovascular outcomes: The cardiac, endothelial function and arterial stiffness in ESRD (CERES) cohort
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Ayer, Amrita, primary, Mills, Claire, additional, Donovan, Catherine, additional, Christenson, Robert H., additional, Ganz, Peter, additional, and Dubin, Ruth F., additional
- Published
- 2019
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28. Application of echocardiographic data in patients with chronic kidney disease
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Dubin, Ruth F., primary
- Published
- 2018
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29. Sex differences in vascular dysfunction and cardiovascular outcomes: The cardiac, endothelial function, and arterial stiffness in ESRD (CERES) study
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Guajardo, Isabella, primary, Ayer, Amrita, additional, Johnson, Alexander D., additional, Ganz, Peter, additional, Mills, Claire, additional, Donovan, Catherine, additional, Scherzer, Rebecca, additional, Shah, Sanjiv J., additional, Peralta, Carmen A., additional, and Dubin, Ruth F., additional
- Published
- 2017
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30. Associations of microvascular dysfunction with cardiovascular outcomes: The cardiac, endothelial function and arterial stiffness in ESRD (CERES) cohort.
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AYER, Amrita, MILLS, Claire, DONOVAN, Catherine, CHRISTENSON, Robert H., GANZ, Peter, and DUBIN, Ruth F.
- Published
- 2019
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31. Determinants of hemodialysis-induced segmental wall motion abnormalities
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Dubin, Ruth F., Beatty, Alexis L., Teerlink, John R., Schiller, Nelson B., Bolger, Ann F., Alokozai, Dean, Peralta, Carmen A., and Johansen, Kirsten L.
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Male ,Kidney Disease ,Left ,Clinical Sciences ,Heart failure ,Bioengineering ,Coronary Artery Disease ,Cardiovascular ,Article ,Kidney Failure ,Cohort Studies ,Ventricular Dysfunction, Left ,Renal Dialysis ,Risk Factors ,Clinical Research ,Ventricular Dysfunction ,Humans ,2.1 Biological and endogenous factors ,Chronic ,Aetiology ,Heart Failure ,Assistive Technology ,end-stage renal disease ,hemodialysis ,Hemodynamics ,Stroke Volume ,Middle Aged ,Urology & Nephrology ,Heart Disease ,Good Health and Well Being ,Echocardiography ,Kidney Failure, Chronic ,Female - Abstract
Patients who demonstrate worsening of cardiac wall motion (WM) during hemodialysis have higher 1-year mortality. We sought to identify risk factors for dialysis-induced WM abnormalities. Additionally, we examined the effects of hemodialysis on other parameters of cardiac function. Forty patients underwent echocardiography directly before dialysis and during the last hour of dialysis (79 dialysis sessions). Candidate predictors for intradialytic worsening of WM included age, a history of heart failure (HF) or coronary artery disease, changes in blood pressure or heart rate, high sensitivity cardiac troponin T and N-terminal brain natriuretic peptide. Among 40 patients, WM worsened segmentally in eight patients (20%), worsened globally in one patient (3%), and improved segmentally in four patients (10%). Diastolic function worsened in 44% of patients, and left ventricular ejection fraction was largely unchanged during dialysis. The case of globally worsened WM occurred in the setting of intradialytic hypertension in a patient without HF. Surprisingly, history of coronary artery disease, hemodynamics, and serologic factors were not associated with worsened segmental WM during dialysis. After adjustment for history of coronary artery disease and other cardiac risk factors, patients with a history of HF had a threefold higher risk of worsening segmental WM during dialysis (RR 3.1, 95% CI [1.1, 9], p = 0.04). In conclusion, patients with a history of clinical HF were at higher risk of intradialytic worsening of segmental WM. Further studies are needed to determine the mechanism of this association and whether cardioprotective medications could ameliorate this adverse cardiac effect of hemodialysis.
- Published
- 2014
32. Association of chronic kidney disease with abnormal cardiac mechanics and adverse outcomes in patients with heart failure and preserved ejection fraction
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Unger, Erin D., primary, Dubin, Ruth F., additional, Deo, Rajat, additional, Daruwalla, Vistasp, additional, Friedman, Julie L., additional, Medina, Crystal, additional, Beussink, Lauren, additional, Freed, Benjamin H., additional, and Shah, Sanjiv J., additional
- Published
- 2015
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33. Sex differences in vascular dysfunction and cardiovascular outcomes: The cardiac, endothelial function, and arterial stiffness in ESRD (CERES) study.
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Guajardo, Isabella, Ayer, Amrita, Johnson, Alexander D., Ganz, Peter, Mills, Claire, Donovan, Catherine, Scherzer, Rebecca, Shah, Sanjiv J., Peralta, Carmen A., and Dubin, Ruth F.
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CHRONIC kidney failure ,ENDOTHELIUM diseases ,ARTERIAL diseases - Abstract
Abstract:
Introduction: Recent studies suggest that women with end‐stage renal disease (ESRD) may have higher rates of mortality than men, but it is unknown whether sex differences in vascular function explain this disparity. The cardiac, endothelial function, and arterial stiffness in ESRD (CERES) study is an ongoing, prospective observational study designed to investigate vascular function, myocardial injury, and cardiovascular outcomes in ESRD.Methods: Among 200 CERES participants (34% women), we evaluated arterial wave reflections as augmentation index normalized to a heart rate of 75 (AIx75), arterial stiffness as pulse wave velocity, and macro‐ and microvascular endothelial dysfunction as flow‐mediated dilation and velocity time integral (VTI). Over a median of 14 months, participants were followed for the composite outcome of cardiovascular hospitalization or all‐cause death.Findings : Women had higher arterial wave reflection (Mean, SD AIx75 30% ± 9% for women vs. 21% ± 10% for men; P < 0.001) and worse microvascular function (VTI 55 ± 30 cm for women vs. 70 ± 27 cm for men; P = 0.007). After multivariable adjustment, female sex remained associated with a 0.5‐SD higher AIx75 (95% CI [0.01, 0.9]) and 0.3‐SD lower VTI (95%CI [0.1, 0.7]). Women experienced higher adjusted rates of the composite outcome (HR 2.5; 95%CI [1.1, 5.6]; P = 0.03), and further adjustment for arterial wave reflection attenuated this risk.Discussion: Vascular dysfunction may partly explain the association of female sex with higher cardiovascular risk and mortality in patients with ESRD. Further studies are needed to explore whether sex differences in vascular function predict long‐term outcomes, and whether hormonal or inflammatory factors explain these associations. [ABSTRACT FROM AUTHOR]- Published
- 2018
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34. Abstract 11639: Interpretation of Diastolic Function in Hemodialysis Patients: The Importance of a Load Independent Index of Left Ventricular Diastolic Compliance
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Dubin, Ruth F, primary, Alokozai, Dean, additional, and Shah, Sanjiv J, additional
- Published
- 2014
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35. The Effects of Frequent Hemodialysis on Left Ventricular Mass, Volumes, and Geometry
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Mishra, Rakesh K., primary and Dubin, Ruth F., additional
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- 2013
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36. Determinants of hemodialysis‐induced segmental wall motion abnormalities
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Dubin, Ruth F., primary, Beatty, Alexis L., additional, Teerlink, John R., additional, Schiller, Nelson B., additional, Bolger, Ann F., additional, Alokozai, Dean, additional, Peralta, Carmen A., additional, and Johansen, Kirsten L., additional
- Published
- 2013
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37. Associations of Tissue Doppler Imaging with NT-pro BNP and hs-TnT: A Pilot Study in End-Stage Renal Disease.
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Dubin, Ruth F., Beatty, Alexis L., Teerlink, John R., Schiller, Nelson B., Alokozai, Dean, and Johansen, Kirsten L.
- Subjects
- *
DOPPLER echocardiography , *ACADEMIC medical centers , *HEART ventricle diseases , *BIOMARKERS , *CONFIDENCE intervals , *HEMODIALYSIS patients , *MULTIVARIATE analysis , *PEPTIDE hormones , *REGRESSION analysis , *RESEARCH funding , *VETERANS' hospitals , *PILOT projects , *DATA analysis software , *DESCRIPTIVE statistics ,CHRONIC kidney failure complications - Abstract
Background Diastolic dysfunction is common and associated with higher mortality in the end-stage renal disease ( ESRD) population. E/E′, a measure derived from tissue Doppler imaging ( TDI), is a correlate of left ventricular ( LV) filling pressures. E/E′ may be viewed as a confirmatory marker of diastolic dysfunction, but it is not routinely used to quantify diastolic dysfunction. Whether E/E′ is associated with N-terminal brain natriuretic peptide ( NT-pro BNP) or high sensitivity troponin T (hs-TnT) in this population is not known. Methods We performed echocardiograms and serology prior to the 2nd or 3rd dialysis session of the week on 35 chronic hemodialysis patients. We compared TDI parameters (E/E′ and E′ alone), traditional categories of diastolic function (normal, impaired, pseudonormal or restrictive), and ejection fraction ( EF) as potential predictors of the outcomes NT-pro BNP and hs-TnT. Results Higher E/E′ was associated with higher NT-pro BNP ( rho 0.48, P = 0.004) and hs-TnT ( rho 0.37, P = 0.03). EF did not have statistically significant associations with NT-pro BNP ( rho −0.2, P = 0.4) or hs-TnT ( rho −0.24, P = 0.16). As compared to patients with normal diastolic function, those with impaired or pseudonormal filling patterns did not have significantly different levels of NT-pro BNP (P = 0.46); patients in traditional categories of worsened diastolic function actually had lower hs-TnT (P = 0.02). The associations of E/E′ with higher NT-pro BNP and hs-TnT persisted after multivariate adjustment for EF, LV mass, and volume status. Conclusions Tissue Doppler imaging may be more useful in evaluating cardiac function than traditional measures of diastolic dysfunction in the ESRD population. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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38. Prevalence and Characteristics of Type 2 Diabetes Mellitus in 9-18 Year-old Children with Diabetic Ketoacidosis.
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Sapru, Anil, Gitelman, Stephen E., Bhatia, Suruchi, Dubin, Ruth F., Newman, Thomas B., and Flori, Heidi
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- 2005
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39. Proteomic Assessment of the Risk of Secondary Cardiovascular Events among Individuals with CKD.
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Deo R, Dubin RF, Ren Y, Wang J, Feldman H, Shou H, Coresh J, Grams ME, Surapaneni AL, Cohen JB, Kansal M, Rahman M, Dobre M, He J, Kelly T, Go AS, Kimmel PL, Vasan RS, Segal MR, Li H, and Ganz P
- Abstract
Background: Cardiovascular risk models have been developed primarily for incident events. Well-performing models are lacking to predict secondary cardiovascular events among people with a history of coronary heart disease, stroke, or heart failure who also have chronic kidney disease (CKD). We sought to develop a proteomics-based risk score for cardiovascular events in individuals with CKD and a history of cardiovascular disease., Methods: We measured 4638 plasma proteins among 1067 participants from the Chronic Renal Insufficiency Cohort (CRIC) and 536 individuals from the Atherosclerosis Risk in Communities Cohort (ARIC). All had non-dialysis-dependent CKD and coronary heart disease, heart failure, or stroke at study baseline. A proteomic risk model for secondary cardiovascular events was derived by elastic net regression in CRIC, validated in ARIC, and compared to clinical models. Biologic mechanisms of secondary events were characterized through proteomic pathway analysis., Results: A 16-protein risk model was superior to the Framingham risk score for secondary events, including a modified score that included estimated glomerular filtration rate (eGFR). In CRIC, the annualized area under the receiver operating characteristic (AUC) within 1 to 5 years ranged between 0.77 and 0.80 for the protein model and 0.57 and 0.72 for the clinical models. These findings were replicated in the ARIC validation cohort. Biologic pathway analysis identified pathways and proteins for cardiac remodeling and fibrosis, vascular disease, and thrombosis., Conclusions: The proteomic risk model for secondary cardiovascular events outperformed clinical models based on traditional risk factors and eGFR., (Copyright © 2024 by the American Society of Nephrology.)
- Published
- 2024
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40. Proteomics and Metabolomics in Kidney Disease, including Insights into Etiology, Treatment, and Prevention.
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Dubin RF and Rhee EP
- Subjects
- Biomarkers metabolism, Humans, Kidney Diseases diagnosis, Kidney Diseases etiology, Kidney Diseases therapy, Predictive Value of Tests, Prognosis, Risk Assessment, Risk Factors, Kidney metabolism, Kidney Diseases metabolism, Metabolome, Metabolomics, Proteome, Proteomics
- Abstract
In this review of the application of proteomics and metabolomics to kidney disease research, we review key concepts, highlight illustrative examples, and outline future directions. The proteome and metabolome reflect the influence of environmental exposures in addition to genetic coding. Circulating levels of proteins and metabolites are dynamic and modifiable, and thus amenable to therapeutic targeting. Design and analytic considerations in proteomics and metabolomics studies should be tailored to the investigator's goals. For the identification of clinical biomarkers, adjustment for all potential confounding variables, particularly GFR, and strict significance thresholds are warranted. However, this approach has the potential to obscure biologic signals and can be overly conservative given the high degree of intercorrelation within the proteome and metabolome. Mass spectrometry, often coupled to up-front chromatographic separation techniques, is a major workhorse in both proteomics and metabolomics. High-throughput antibody- and aptamer-based proteomic platforms have emerged as additional, powerful approaches to assay the proteome. As the breadth of coverage for these methodologies continues to expand, machine learning tools and pathway analyses can help select the molecules of greatest interest and categorize them in distinct biologic themes. Studies to date have already made a substantial effect, for example elucidating target antigens in membranous nephropathy, identifying a signature of urinary peptides that adds prognostic information to urinary albumin in CKD, implicating circulating inflammatory proteins as potential mediators of diabetic nephropathy, demonstrating the key role of the microbiome in the uremic milieu, and highlighting kidney bioenergetics as a modifiable factor in AKI. Additional studies are required to replicate and expand on these findings in independent cohorts. Further, more work is needed to understand the longitudinal trajectory of select protein and metabolite markers, perform transomics analyses within merged datasets, and incorporate more kidney tissue-based investigation., (Copyright © 2020 by the American Society of Nephrology.)
- Published
- 2020
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41. Associations of Conventional Echocardiographic Measures with Incident Heart Failure and Mortality: The Chronic Renal Insufficiency Cohort.
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Dubin RF, Deo R, Bansal N, Anderson AH, Yang P, Go AS, Keane M, Townsend R, Porter A, Budoff M, Malik S, He J, Rahman M, Wright J, Cappola T, Kallem R, Roy J, Sha D, and Shlipak MG
- Subjects
- Aged, Echocardiography, Female, Follow-Up Studies, Heart Failure physiopathology, Heart Ventricles diagnostic imaging, Humans, Hypertrophy, Left Ventricular diagnostic imaging, Hypertrophy, Left Ventricular physiopathology, Incidence, Male, Middle Aged, Organ Size, Stroke Volume, Cause of Death, Heart Failure epidemiology, Heart Ventricles pathology, Hypertrophy, Left Ventricular epidemiology, Renal Insufficiency, Chronic epidemiology
- Abstract
Background and Objectives: Heart failure is the most frequent cardiac complication of CKD. Left ventricular hypertrophy is common and develops early in CKD, but studies have not adequately evaluated the association of left ventricular mass index with heart failure incidence among men and women with CKD., Design, Setting, Participants, & Measurements: We evaluated echocardiograms of 2567 participants without self-reported heart failure enrolled in the Chronic Renal Insufficiency Cohort Study. Two-dimensional echocardiograms were performed at the year 1 study visit and interpreted at a central core laboratory. Left ventricular mass index was calculated using the linear method, indexed to height
2.7 , and analyzed using sex-specific quartiles. The primary outcomes of incident heart failure and all-cause mortality were adjudicated over a median of 6.6 (interquartile range, 5.7-7.6) years., Results: Among 2567 participants, 45% were women, and 54% were nonwhite race; mean (SD) age was 59±11 years old, and mean eGFR was 44±17 ml/min per 1.73 m2 . During a median follow-up period of 6.6 years, 262 participants developed heart failure, and 470 participants died. Compared with participants in the first quartile of left ventricular mass index, those in the highest quartile had higher rates of incident heart failure (hazard ratio, 3.96; 95% confidence interval, 1.96 to 8.02) and mortality (hazard ratio, 1.86; 95% confidence interval, 1.22 to 2.85), even after adjustment for B-type natriuretic peptide, troponin T, mineral metabolism markers, and other cardiovascular disease risk factors. Those in the lowest quartile of ejection fraction had higher rates of incident heart failure (hazard ratio, 3.01; 95% confidence interval, 1.94 to 4.67) but similar mortality rates (hazard ratio, 1.18; 95% confidence interval, 0.89 to 1.57) compared with those in the highest quartile. Diastolic dysfunction was not significantly associated with heart failure or death., Conclusions: Among persons with CKD and without history of cardiovascular disease, left ventricular mass index is strongly associated with incident heart failure, even after adjustment for major cardiovascular risk factors and biomarkers., (Copyright © 2016 by the American Society of Nephrology.)- Published
- 2017
- Full Text
- View/download PDF
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