Peter A McCullough

Baylor Hamilton Heart and Vascular Hospital, Dallas, Texas, United States

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Publications (506)2609.81 Total impact

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    ABSTRACT: The association between chronic kidney disease (CKD) and cardiovascular disease (CVD) is well established, and there is mounting evidence of interorgan cross talk that may accelerate pathologic processes and the progression of organ dysfunction in both systems. This process, termed cardiorenal syndrome (CRS) by the Acute Dialysis Quality Initiative, is considered a major health problem: patients with CKD and CVD are at much higher risk of mortality than patients with either condition alone. To date, the majority of CRS research has focused on neurohormonal mechanisms and hemodynamic alterations. However, mounting evidence suggests that abnormalities in the normal pathophysiology of the bone-mineral axis, iron, and erythropoietin play a role in accelerating CKD and CVD. The goal of this article is to review the role and interrelated effects of the bone-mineral axis and anemia in the pathogenesis of chronic CRS. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
  • Peter A McCullough, Ankit Mehta, Harold Szerlip
    Journal of the American College of Cardiology 12/2014; 64(25):2763-4. DOI:10.1016/j.jacc.2014.09.065 · 15.34 Impact Factor
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    ABSTRACT: Abstract Objective: Neutrophil gelatinase-associated lipocalin (NGAL) is produced in response to tubular injury. Contrast-induced acute kidney injury (CI-AKI) is associated with adverse outcomes in chronic kidney disease (CKD) patients. We sought to characterize blood NGAL level and the degree of kidney injury in CKD patients who underwent coronary angiography. Methods: This study was a prospective, blinded assessment of blood samples obtained from patients with estimated glomerular filtration rates (eGFRs) between 15 and 90 mL/min/1.73 m(2) undergoing elective coronary angiography with iodinated contrast. Blood NGAL and serum creatinine were measured at baseline, 1, 2, 4, 6, 12, 24 and 48 h after contrast administration. Results: A total of 63 subjects with a mean eGFR of 48.17 ± 16.45 mL/min/1.73 m(2) were enrolled. There was a graded increase in baseline NGAL levels across worsening stages of CKD (p = 0.0001). Post-procedure NGAL increased from baseline in each stage of CKD. Eight (12.7%) patients were diagnosed with CI-AKI by diagnostic criteria of 2012 KDIGO definition of CI-AKI, and seven (11.1%) patients developed subclinical CI-AKI defined by a twofold or greater rise in NGAL. There was no relationship between baseline eGFR and diabetes on the composite outcome of subclinical and clinical CI-AKI. Conclusions: Baseline and post-procedure NGAL are progressively elevated according to the baseline stage of CKD. Using a twofold rise in NGAL, 46.7% of composite CI-AKI is detected and complements the 53.3% of cases identified using KDIGO criteria. Traditional risk predictors were not independently associated with this composite outcome.
    Renal Failure 12/2014; 37(2):1-5. DOI:10.3109/0886022X.2014.991994 · 0.78 Impact Factor
  • Timothy Ball, Kevin Wheelan, Peter A McCullough
    Journal of the American College of Cardiology 12/2014; 64(23):2483-5. DOI:10.1016/j.jacc.2014.09.052 · 15.34 Impact Factor
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    ABSTRACT: This US, multicenter, observational study assessed the CKD prevalence in adult patients with type-2 diabetes mellitus (T2DM) and characterized the proportion of detected and undiagnosed CKD in the primary care setting using the following: a clinician survey; a patient physical exam and medical history; a single blood draw for estimated glomerular filtration rate (eGFR) and glycosolated hemoglobin (HbA1c); urine dipstick for protein; urine albumin-creatinine ratio (ACR); two patient quality of life questionnaires; and a 15-month medical record review. The study consisted of 9339 adults with T2DM and 466 investigator sites. Of the 9339 enrolled, 9307 had complete data collection for analysis. The 15-month retrospective review showed urine protein, urine ACR, and eGFR testing were not performed in 51.4%, 52.9% and 15.2% of individuals, respectively. Of the 9307 patients, 5036 (54.1%) had Stage 1-5 CKD based on eGFR and albuminuria; however, only 607 (12.1%) of those patients were identified as having CKD by their clinicians. Clinicians were more successful in diagnosing patients with Stage 3-5 CKD than Stages 1 and 2. There were no differences in clinicians' likelihood of identification of CKD based on practice setting, number of years in practice, or self-reported patients seen per week. Awareness or patient self-reported CKD was 81.1% with practitioner detection versus 2.6% in the absence of diagnosis. Primary care of T2DM demonstrates recommended urine CKD testing is underutilized, and CKD is significantly under-diagnosed. This is the first study to show CKD detection is associated with awareness.
    PLoS ONE 11/2014; 9(11):e110535. DOI:10.1371/journal.pone.0110535 · 3.53 Impact Factor
  • Peter A. McCullough, John L. Jefferies
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    ABSTRACT: Acute kidney injury complicates decompensated heart failure in ∼33% of cases and is associated with morbidity and mortality, thus, we sought to systematically review this topic in order to summarize novel diagnostic and therapeutic approaches.Methods Structured PubMed searches on these topics were conducted in February 2014 and relevant literature was identified. The PubMed search identified a total of 192 articles that were individually screened for inclusion in this analysis and 58 were included.ResultsAcute kidney injury, defined by substantial rises in serum creatinine, is consistently associated with prolonged length of stay, rehospitalization, and mortality. Biomarker studies suggested that natriuretic peptides are prognostic for shorter and longer term mortality. Novel proteins indicating kidney damage and albumin in the urine are associated with acute kidney injury. The most promising acute pharmacologic treatment appears to be serelaxin, which has been shown to improve acute heart failure symptoms, hemodynamic parameters, and renal function.Conclusions The presence of acute kidney injury results in worse clinical outcomes for patients with acute heart failure. Novel biomarkers and therapies hold the promise of improving both cardiac and renal outcomes in these patients.
    The American Journal of Medicine 11/2014; 128(3). DOI:10.1016/j.amjmed.2014.10.035 · 5.30 Impact Factor
  • John K. Roberts, Peter A. McCullough
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    ABSTRACT: Coronary heart disease is highly prevalent in patients with CKD, and survival after acute coronary syndrome (ACS) is worse compared with the general population. Many trials that define guidelines for cardiovascular disease excluded patients with kidney disease, leaving a gap between the evidence base and clinical reality. The underlying pathophysiology of vascular disease appears to be different in the setting of CKD. Patients with CKD are more likely to present with myocardial infarction and less likely to be diagnosed with ACS on admission compared with the general population. Patients with CKD appear to benefit with angiography and revascularization compared with medical management alone. However, the increased risk of in-hospital bleeding and risk of contrast-induced acute kidney injury are 2 factors that can limit overall benefit for some. Thus, judicious application of available therapies for the management of ACS is warranted to extend survival and reduce hospitalizations in this high-risk population. In this review, we highlight the clinical challenges and potential solutions for managing ACS in patients with CKD.
    Advances in Chronic Kidney Disease 11/2014; 21(6). DOI:10.1053/j.ackd.2014.08.005 · 1.94 Impact Factor
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    ABSTRACT: A phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor-erythroid-2-related factor-2 (Nrf2) activator, slows progression to end-stage renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention.
    Journal of Cardiac Failure 10/2014; DOI:10.1016/j.cardfail.2014.10.001 · 3.07 Impact Factor
  • Peter A McCullough, Poorya Fazel, James W Choi
    JACC Cardiovascular Imaging 10/2014; 7(10):1011-2. DOI:10.1016/j.jcmg.2014.08.001 · 6.99 Impact Factor
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    ABSTRACT: Acute kidney injury (AKI) remains a deadly condition. Tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein (IGFBP)7 are two recently discovered urinary biomarkers for AKI. We now report on the development, and diagnostic accuracy of two clinical cutoffs for a test using these markers.
    Nephrology Dialysis Transplantation 09/2014; 29(11). DOI:10.1093/ndt/gfu292 · 3.49 Impact Factor
  • Peter Andrew McCullough, William Clifford Roberts
    The American Journal of Cardiology 09/2014; 114(11). DOI:10.1016/j.amjcard.2014.08.034 · 3.43 Impact Factor
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    ABSTRACT: Albuminuria is a strong predictor of diabetic nephropathy chronic kidney disease outcomes. Yet, therapeutic albuminuria-lowering has not consistently translated into a reduction in clinical events suggesting the involvement of additional pathogenic factors. Our hypothesis is that anti-endothelial cell autoantibodies play a role in development and progression in diabetic nephropathy. We determined anti-endothelial cell antibody (AECA) bioactivity in protein A-elutes of baseline plasma in 305 participants in the VA NEPHRON-D study, a randomized trial of angiotensin receptor blocker (ARB) or dual ARB plus angiotensin-converting enzyme inhibitor therapy in type 2 diabetes with proteinuric nephropathy. Thirty-eight percent (117/305) of participants had significantly reduced endothelial cell survival ( ≤80%) in the IgG fraction of plasma. A VA NEPHRON-D primary endpoint [end-stage renal disease (ESRD), significant reduction in estimated glomerular filtration rate, or death] was experienced by 58 individuals. In adjusted Cox regression analysis, there was a significant interaction effect of baseline anti-endothelial cell-mediated cell survival and albuminuria on the hazard rate (HR) for primary composite endpoint (P = 0.017). Participants lacking strongly inhibitory antibodies with albuminuria ≥1 g/g creatinine had a significantly increased primary event hazard ratio, 3.41 - 95% confidence intervals (CI 1.84-6.33; P < 0.001) compared to those lacking strongly inhibitory antibodies with lower baseline albuminuria ( <1 g/g creatinine). These results suggest that anti-endothelial cell antibodies interact significantly with albuminuria in predicting the composite endpoint of death, ESRD, or substantial decline in renal function in older, adult type 2 diabetic nephropathy.
    Frontiers in Endocrinology 08/2014; 5:128. DOI:10.3389/fendo.2014.00128
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    ABSTRACT: Contrast-induced acute kidney injury (CI-AKI) is associated with increased morbidity and mortality after percutaneous coronary interventions and is a patient safety objective of the National Quality Forum. However, no formal quality improvement program to prevent CI-AKI has been conducted. Therefore, we sought to determine whether a 6-year regional multicenter quality improvement intervention could reduce CI-AKI after percutaneous coronary interventions.
    Circulation Cardiovascular Quality and Outcomes 07/2014; 7(5). DOI:10.1161/CIRCOUTCOMES.114.000903 · 5.66 Impact Factor
  • Peter A. McCullough
    07/2014; 3(3):357–362. DOI:10.1016/j.iccl.2014.03.002
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    ABSTRACT: Intravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics.
    Critical care (London, England) 06/2014; 18(3):R134. DOI:10.1186/cc13952
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    ABSTRACT: Background: Bardoxolone methyl, an Nrf2-activating and nuclear factor-κB-inhibiting semisynthetic oleanane triterpenoid compound, was evaluated in a phase 3 trial (BEACON) in patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD). The trial was terminated because of an increase in heart failure events in the bardoxolone methyl group, many of which appeared related to fluid retention. Thus, additional analyses were conducted to explain these serious adverse events. Methods: Patients (n = 2,185) were randomized to receive once-daily bardoxolone methyl (20 mg) or placebo. Twenty-four-hour urine collections were analyzed in a subset of the BEACON population and from a separate, open-label pharmacology study in patients with stage 3b/4 CKD and T2DM administered 20 mg bardoxolone methyl once daily for 56 consecutive days. Results: Bardoxolone-methyl-treated patients in the BEACON substudy had a clinically meaningful reduction in urine volume and sodium excretion at week 4 relative to baseline (p < 0.05), and a separate study revealed that decreased sodium excretion and urine output occurred in some patients with stage 4 CKD but not those with stage 3b CKD. The clinical phenotype of fluid overload and heart failure in BEACON was similar to that observed with endothelin receptor antagonists in advanced CKD patients, and preclinical data demonstrate that bardoxolone methyl modifies endothelin signaling. Conclusions: The totality of the evidence suggests that through modulation of the endothelin pathway, bardoxolone methyl may pharmacologically promote acute sodium and volume retention and increase blood pressure in patients with more advanced CKD. © 2014 S. Karger AG, Basel.
    American Journal of Nephrology 06/2014; 39(6):499-508. DOI:10.1159/000362906 · 2.65 Impact Factor
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    ABSTRACT: Dabigatran etexilate, was found to be effective for stroke prevention in patients with non-valvular atrial fibrillation. Given its predictable pharmacodynamics, laboratory monitoring is not required. Moreover, the risks of overall bleeding, intracranial bleeding, and life-threatening hemorrhage from dabigatran were found to be lower than warfarin. However, a higher risk of gastrointestinal (GI) bleeding caused by dabigatran from the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial has raised the concern regarding clinical outcomes of patients with GI bleeding caused by dabigatran compared with warfarin.
  • Peter A McCullough
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    ABSTRACT: Abstract Heart failure is a complex mechanical and neurohormonal syndrome where the left ventricle fails as a pump, resulting in stasis of blood in the lungs and the periphery resulting in the cardial features of effort intolerance, fatigue, and peripheral edema. As part of the neurohormonal and local mechanical strain, tissue macrophages resident in the myocardium secrete galectin-3 which is a paracrine and endocrine factor which stimulates additional macrophages, pericytes, myofibroblasts, and fibroblasts to proliferate and secrete procollagen I which is irreversibly crosslinked resulting in myocardial fibrosis. In the general population, normal plasma concentrations of galectin-3 are <11.0 ng/mL. Galectin-3 measured in blood has been shown to: 1) identify increased risk for new onset heart failure in healthy middle-aged adults; 2) predict cardiac failure in patients after acute coronary syndromes; 3) help establish the diagnosis of heart failure with preserved ejection fraction in patients presenting with exercise intolerance; and 4) aid in the prognosis of heart failure with preserved and reduced left ventricular ejection fraction. This manuscript will present practical real case management in these applications to highlight the importance of this new in vitro diagnostic test.
    Clinical Chemistry and Laboratory Medicine 05/2014; 52(10). DOI:10.1515/cclm-2014-0278 · 2.96 Impact Factor
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    ABSTRACT: Structural heart disease is highly prevalent in patients with chronic kidney disease requiring dialysis. More than 80% of end-stage renal disease (ESRD) patients are reported to have cardiovascular disease (CVD). This observation has enormous clinical relevance, as the leading causes of death for ESRD patients are of CVD etiology, including heart failure, myocardial infarction, and sudden cardiac death. The two systems most commonly used to classify the severity of heart failure are the New York Heart Association (NYHA) functional classification and the American Heart Association/American College of Cardiology (AHA/ACC) staging system. With rare exceptions, ESRD patients who do not receive renal replacement therapy (RRT) develop signs and symptoms of heart failure, including dyspnea and edema due to inability of the severely diseased kidneys to excrete sodium and water. Thus, by definition, nearly all ESRD patients develop a symptomatology consistent with heart failure if fluid removal by RRT is delayed. Neither the AHA/ACC heart failure staging nor the NYHA functional classification system identifies the variable symptomatology that ESRD patients experience depending upon whether evaluation occurs before or after fluid removal by RRT. Consequently, the incidence, severity, and outcomes of heart failure in ESRD patients are poorly characterized. The 11th Acute Dialysis Quality Initiative has identified this issue as a critical unmet need for the proper evaluation and treatment of heart failure in patients with ESRD. We propose a classification schema based on patient-reported dyspnea assessed both pre- and post-ultrafiltration, in conjunction with echocardiography.
    Journal of the American College of Cardiology 04/2014; 63(13). DOI:10.1016/j.jacc.2014.01.020 · 15.34 Impact Factor
  • Peter A McCullough
    American Journal of Kidney Diseases 04/2014; 64(1). DOI:10.1053/j.ajkd.2014.03.006 · 5.76 Impact Factor

Publication Stats

17k Citations
2,609.81 Total Impact Points


  • 2013–2015
    • Baylor Hamilton Heart and Vascular Hospital
      Dallas, Texas, United States
    • Detroit Medical Center
      Detroit, Michigan, United States
    • University of Arkansas at Little Rock
      Little Rock, Arkansas, United States
  • 2014
    • Arkansas Heart Hospital
      Little Rock, Arkansas, United States
    • Baylor University
      Waco, Texas, United States
  • 2012–2013
    • St. John's Medical Center
      Jackson, Wyoming, United States
    • Saint Luke's Hospital (NY, USA)
      New York City, New York, United States
    • Children's Hospital of Michigan
      Detroit, Michigan, United States
  • 2010–2013
    • St. John Providence Health System
      Detroit, Michigan, United States
    • University of Alberta
      • Division of Critical Care Medicine
      Edmonton, Alberta, Canada
    • Beaumont Health System
      Detroit, Michigan, United States
    • University of California, Los Angeles
      Los Ángeles, California, United States
    • Duke University Medical Center
      • Division of General Internal Medicine
      Durham, NC, United States
  • 2001–2012
    • University of Missouri - Kansas City
      • • "Saint Luke's" Mid America Heart Institute
      • • School of Medicine
      • • Department of Internal Medicine
      Kansas City, MO, United States
    • Lenox Hill Hospital
      New York City, New York, United States
  • 1997–2012
    • William Beaumont Army Medical Center
      El Paso, Texas, United States
  • 2011
    • Northern New England Cardiovascular Research Study Group
      Lebanon, New Hampshire, United States
    • University of Missouri
      • Department of Internal Medicine
      Columbia, Missouri, United States
    • Oakland University
      Рочестер, Michigan, United States
  • 2010–2011
    • Cedars-Sinai Medical Center
      • Division of Cardiology
      Los Angeles, CA, United States
  • 2003–2010
    • University of Texas Southwestern Medical Center
      • Division of Cardiology
      Dallas, Texas, United States
    • National University (California)
      San Diego, California, United States
  • 2008
    • University of Louisville
      Louisville, Kentucky, United States
    • Eastern Virginia Medical School
      • School of Medicine
      Norfolk, VA, United States
  • 2007
    • Wayne State University
      Detroit, Michigan, United States
    • The National Kidney Foundation
      New York, New York, United States
    • Columbia University
      New York, New York, United States
    • University of Chicago
      • Department of Medicine
      Chicago, Illinois, United States
  • 2006
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
    • Wright State University
      Dayton, Ohio, United States
    • Southeast Renal Research Institute
      Chattanooga, Tennessee, United States
    • Universitair Ziekenhuis Ghent
      Gand, Flanders, Belgium
  • 2004–2006
    • University of California, San Diego
      • Division of Cardiology
      San Diego, California, United States
    • VA San Diego Healthcare System
      San Diego, California, United States
    • St. Luke's Hospital
      Cedar Rapids, Iowa, United States
    • The Ohio State University
      Columbus, Ohio, United States
  • 2002–2006
    • University of Oslo
      • Division of Medicine
      Oslo, Oslo, Norway
  • 2001–2006
    • Truman Medical Center
      Kansas City, Kansas, United States
  • 2003–2004
    • Duke University
      Durham, North Carolina, United States
  • 1998–2003
    • Henry Ford Health System
      • Department of Emergency Medicine
      Detroit, Michigan, United States
  • 2000–2001
    • Albany Medical College
      • Division of Cardiology
      Albany, NY, United States
  • 1998–2001
    • Henry Ford Hospital
      • Department of Internal Medicine
      Detroit, MI, United States