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Collection Highlights

Cardiac Catheterization for Congenital Heart Disease From

Fetal Life to Adulthood 1st Edition Gianfranco Butera

Frailty and Kidney Disease: A Practical Guide to Clinical

Management Carlos Guido Musso

Polycystic Kidney Disease Benjamin D. Cowley

Chronic Kidney Disease, Dialysis, and Transplantation: A

Companion to Brenner and Rector’s The Kidney 4th Edition
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chemical laboratory : a practical approach Second Edition
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Resistant Hypertension in Chronic Kidney Disease 1st

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Kidney Biomarkers: Clinical Aspects and Laboratory

Determination 1st Edition Seema S. Ahuja (Editor)
Kidney Disease in the
Cardiac Catheterization
Laboratory

A Practical Approach
Janani Rangaswami
Edgar V. Lerma
Peter A. McCullough
Editors

123
Kidney Disease in the Cardiac Catheterization
Laboratory
Janani Rangaswami • Edgar V. Lerma
Peter A. McCullough
Editors

Kidney Disease in the

Cardiac Catheterization
Laboratory
A Practical Approach
Editors
Janani Rangaswami Edgar V. Lerma
Einstein Medical Center/Thomas Jefferson UIC/Advocate Christ Medical Center
University Department of Medicine
Department of Medicine/Nephrology Chicago, Il
Philadelphia, PA USA
USA

Peter A. McCullough
Baylor University Medical Center, Baylor
Heart and Vascular Hospital
Department of Internal Medicine, Texas A
& M College of Medicine, Division of
Cardiology
Dallas, TX
USA

ISBN 978-3-030-45413-5    ISBN 978-3-030-45414-2 (eBook)

https://doi.org/10.1007/978-3-030-45414-2

© Springer Nature Switzerland AG 2020

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To my family, mentors and patients – thanks for
your support and guidance each step of the way.
­—Janani Rangaswami.

To all my mentors, and friends, at the University

of Santo Tomas Faculty of Medicine and Surgery
in Manila, Philippines, and Northwestern
University Feinberg School of Medicine in
Chicago, IL, who have, in one way or another,
influenced and guided me to become the
physician that I am...
To all the medical students, interns, and
residents at Advocate Christ Medical Center and
Macneal Hospital, whom I have taught or
learned from, especially those who eventually
decided to pursue Nephrology as a career...
To my parents and my brothers, without whose
unwavering love and support through the good
and bad times, I would not have persevered and
reached my goals in life…
Most especially, to my two lovely and precious
daughters Anastasia Zofia and Isabella Ann,
whose smiles and laughter constantly provide me
unparalleled joy and happiness; and my very
loving and understanding wife Michelle, who has
always been supportive of my endeavors both
personally and professionally, and who sacrificed
a lot of time and exhibited unwavering patience
as I devoted a significant amount of time and
effort to this project. Truly, they provide me with
motivation and inspiration.
—Edgar V. Lerma.

This work is dedicated to the steadfastness and

providence of my wife Maha, and to the energy
and excitement of our young professional
children Haley and Sean.
—Peter A. McCullough.
Foreword

The pathophysiological interactions between the heart and kidneys represent today
an interesting and cutting-edge topic of discussion among physicians and students.
Since the first description of the new definition/classification of the cardio-renal
syndrome, an increasing number of publications and dedicated meetings have
been noted worldwide. This textbook, edited by Janani Rangaswami, Edgar
V. Lerma, and Peter A. McCullough, is further demonstration of the growing inter-
est in this discipline. The book represents an answer to a medical need and to an
educational demand that has become evident in recent years. The table of content
well describes the pathway from basic research and physiology, to the pathophysi-
ological foundation of combined cardiovascular and kidney disease, to finally
reach the basis, modality, and the nuances of complex cardiac catheterization labo-
ratory procedures in patients with kidney disease. The innovative aspect of the
book is the multidisciplinary approach to a patient that may or will encounter
mixed cardiorenal disease. The increased use of complex cardiovascular proce-
dures in patients with kidney disease has led to new types of complications that
must be dealt with by a combined task force made of specialists of different disci-
plines. The last part of the book well describes the utility of the cardio-nephrology
collaborative effort in the cardiac catheterization laboratory. Years ago, I advo-
cated the advent of a critical care nephrology multidisciplinary team. Recently we
applied the concept of the nephrology rapid-response team in case of early preven-
tion/detection of acute kidney injury. Other experiences use Artificial Intelligence
as a basis for a multidisciplinary approach to the critically ill patient. This book
fills a gap in the area of catheterization laboratory where cardiologists and nephrol-
ogists should be working together to avoid major complications and mitigate pos-
sible detrimental effects of the numerous procedures, often performed in an elderly
as well as comorbid population where the susceptibility to kidney insults are at the
highest levels.

vii
viii Foreword

I must, therefore, congratulate the authors and editors for their valuable contribu-
tions to this textbook. I expect this book to become a reference for practicing physi-
cians and specialists as well as for students and fellows interested in expanding their
knowledge in this complex, yet exciting area of medicine.

Padua, Italy
Claudio Ronco
Vicenza, Italy
Preface

The link between heart and kidney disease is of historical importance in medicine,
probably first reported in the literature in 1836 by Sir Richard Bright, widely
regarded as the father of modern nephrology. From that initial notation to the cur-
rent times, we are faced with an epidemic of cardiovascular and kidney disease
stemming from the common soil of vascular risk factors such as hypertension, dia-
betes, and obesity in an aging population. In parallel to this increasing burden of
cardiorenal disease, there have been major advances in the field of interventional
cardiology with the advent of cutting-edge technologies, minimally invasive opera-
tor techniques, and the ability to modify the course of formerly inoperable and
highly complex coronary, peripheral vascular, and valvular procedures. In this con-
text, it is imperative for the interventional cardiologist as well as the nephrologist to
understand the nuances of the interface between cardiovascular and kidney disease
in detail, and to deliver optimal interventional cardiac and vascular therapies in
patients with dual organ disease. Patients with chronic kidney disease have tradi-
tionally been excluded from high-quality randomized trials in cardiovascular medi-
cine and routinely get sub-optimally treated or excluded from potentially beneficial
interventions, despite the well-known disproportionately high burden of cardiovas-
cular disease in this population. Fortunately for these vulnerable patients, the recent
advances in interventional cardiology have opened new avenues of therapy for
patients with advanced chronic kidney disease in the cardiac catheterization labora-
tory, working to reduce the therapeutic nihilism that is ingrained in clinical practice.
This textbook assembles the collective expertise, experience, and viewpoints of
international leaders in the field of interventional cardiology and nephrology to
summarize the complex interface between these two specialties in the setting of the
cardiac catheterization laboratory. Authors have contributed to this field with new
pioneering interventional strategies and techniques, trial leadership, and patient
advocacy that allow the reader to benefit from a comprehensive and balanced view
of this field and apply those principles in their clinical practice. This textbook will
be immensely useful to practicing interventional cardiologists, nephrologists,
trainee physicians, as well as advanced care practitioners in the fields of cardiology
and nephrology as a single authoritative source for understanding the interplay

ix
x Preface

between cardiovascular and kidney disease in the cardiac catheterization laboratory.

We hope that the interdisciplinary cross-talk in this textbook will serve as a catalyst
for future multidisciplinary cardiorenal care models and research collaborations,
which would be the best use of the collective expertise of the authors that is sum-
marized in this volume.
We wish to thank each author and writing group for their valuable input and time
as contribution to this project. We also thank Greg Sutorius and Andy Kwan of
Springer International for their leadership in making this textbook a reality. This
textbook would not have been possible without the diligence and hard work of the
developmental editor Michele Aiello, whom we would like to thank on behalf of all
the authors and the editorial team. We hope to see this assemblage be part of the
growth in this dual specialty field and help with the delivery of the very best clinical
practice to patients with the need for cardiovascular interventions in the setting of
chronic kidney disease, to reduce complications, morbidity, and mortality in this
fragile population.

Philadelphia, PA, USA  Janani Rangaswami,

Chicago, IL, USA  Edgar V. Lerma,
Dallas, TX, USA Peter A. McCullough,
Contents

Part I Atherosclerotic Cardiovascular Disease Burden in Chronic

Kidney Disease
1 The Burden of Coronary Artery Disease
in Chronic Kidney Disease������������������������������������������������������������������������   3
Sylvia Biso and Amer K. Ardati
2 Non-invasive Testing in the Diagnosis of Ischemic
Heart Disease in CKD: Scope, Pitfalls, and Future Directions�������������� 19
Michelle D. Carlson and Gautam R. Shroff
3 Peripheral Arterial Disease in Chronic Kidney Disease:
Disease Burden, Outcomes, and Interventional Strategies�������������������� 37
Harsha S. Nagarajarao, Chandra Ojha, Archana Kedar,
and Debabrata Mukherjee
4 Cardiovascular Impact of Atherosclerotic
Renovascular Disease�������������������������������������������������������������������������������� 69
Gates B. Colbert and Harold M. Szerlip

Part II Therapeutic Considerations with Revascularization

in Chronic Kidney Disease
5 Therapeutic Considerations with Revascularization
in Chronic Kidney Disease: Radial Versus
Femoral Arterial Access���������������������������������������������������������������������������� 85
Giuseppe Andò, Felice Gragnano, Paolo Calabrò, and Marco
Valgimigli
6 Antiplatelet Agent Choice and Platelet
Function Testing in CKD�������������������������������������������������������������������������� 103
Udaya S. Tantry, Amit Rout, Rahul Chaudhary, and Paul A. Gurbel

xi
xii Contents

7 Choice of Stents and Clinical Outcomes in Patients

with Chronic Kidney Disease�������������������������������������������������������������������� 119
Shawn X. Li and Usman Baber
8 Revascularization Strategies in Chronic Kidney Disease:
Percutaneous Coronary Interventions Versus Coronary
Artery Bypass Graft���������������������������������������������������������������������������������� 133
Stephani C. Wang, Elizabeth L. Nichols, Michael E. Farkouh,
and Mandeep S. Sidhu
9 Approach to Revascularization in the Potential
Kidney Transplant Recipient�������������������������������������������������������������������� 145
Gustavo Soares Guandalini and Sripal Bangalore
10 Nephrology Consultative Approach and Risk Stratification
Prior to Revascularization in Chronic Kidney Disease�������������������������� 165
Roy O. Mathew, Valerian Fernandes, and Sripal Bangalore

Part III Acute Kidney Injury in the

Catheterization Laboratory: Part I
11 Contrast-Induced Acute Kidney Injury: Epidemiology,
Risk Stratification, and Prognosis������������������������������������������������������������ 183
Jehan Zahid Bahrainwala, Amanda K. Leonberg-Yoo,
and Michael R. Rudnick
12 Pathophysiology of Contrast Induced Acute Kidney Injury������������������ 209
Hector M. Madariaga, Tapati Stalam, Ami M. Patel,
and Beje Thomas
13 Prevention of Contrast-Induced AKI: Summary of
Volume Optimization Strategies �������������������������������������������������������������� 225
Jaspreet S. Arora, Brandon Kai, and Somjot S. Brar
14 Operator and Intraprocedural Strategies to Reduce
Contrast-Induced Acute Kidney Injury�������������������������������������������������� 235
Sanjog Kalra, Ziad Anwar Ali, Dimitri Karmpaliotis,
Ajay J. Kirtane, and Jeffrey W. Moses

Part IV Acute Kidney Injury in the Catheterization

Laboratory: Part II
15 Effect of Acute Mechanical Circulatory Support
on Kidney Function����������������������������������������������������������������������������������� 259
Shiva K. Annamalai, Lena E. Jorde, Carlos D. Davila,
and Navin K. Kapur
Contents xiii

16 Renal Athero-embolic Disease: An Underdiagnosed

Entity in Cardiac Catheterization������������������������������������������������������������ 275
Shweta Punj and Jennifer Tuazon
17 Acute Kidney Injury After Transcatheter Aortic
Valve Replacement ������������������������������������������������������������������������������������ 285
Ricardo J. Cigarroa and Sammy Elmariah
18 Impact of Kidney Disease on Catheter-­Based Mitral Valve
Interventions���������������������������������������������������������������������������������������������� 299
Nikoloz Koshkelashvili, Jose F. Condado, and Vasilis Babaliaros
19 Contrast-Induced Nephropathy After Peripheral Vascular
Intervention������������������������������������������������������������������������������������������������ 313
Michael James Ewing, Angela L. Gucwa, and John F. Eidt

Part V Catheter Based Reno-Vascular Interventions

20 Renal Artery Stenosis: State of the Art in the Diagnosis
and Management���������������������������������������������������������������������������������������� 337
Sanjum S. Sethi and Sahil A. Parikh
21 Renal Denervation: Physiology, Scope, and Current Evidence ������������ 349
Márcio Galindo Kiuchi and Markus P. Schlaich
22 Forced Matched Diuresis: Role in Renal Protection
in the Cardiac Catheterization Laboratory�������������������������������������������� 367
Richard Solomon and Nina Narasimhadevara

Part VI Role of Hemodynamic Evaluation

in the Catheterization Laboratory
23 Traditional and Novel Invasive Hemodynamic Indices
in the Evaluation of Congestive Heart Failure
in Cardiorenal Syndrome�������������������������������������������������������������������������� 379
Mahek Shah, Brijesh Patel, Sahil Agrawal, and Ulrich P. Jorde
24 Pulmonary Hypertension in Chronic Kidney Disease���������������������������� 397
Salvatore P. Costa

Part VII Utility of the Cardio-Nephrology Collaborative

in the Cardiac Catheterization Laboratory
25 The Economic Impact of Kidney Disease in the Cardiac
Catheterization Laboratory���������������������������������������������������������������������� 409
Justin M. Cloutier, David W. Allen, and Paul Komenda
xiv Contents

26 Biomarkers of Acute Kidney Injury and Scope of Utilization

in the Cardiac Catheterization Laboratory�������������������������������������������� 429
Ladan Golestaneh and Abby Miriam Basalely
27 A Call to Action to Develop Integrated Curricula
in Cardiorenal Medicine���������������������������������������������������������������������������� 449
Claudio Ronco, Federico Ronco, and Peter A. McCullough
Index������������������������������������������������������������������������������������������������������������������ 463
Contributors

Sahil Agrawal, MD Department of Cardiology, Saint Francis Hospital,

Tulsa, OK, USA
Ziad Anwar Ali, MD, DPhil Cardio-Renal Services, New York Presbyterian
Hospital/Columbia University Medical Center, Center for Interventional Vascular
Therapy, New York, NY, USA
David W. Allen, MD, FRCPC Department of Medicine, Section of Cardiology,
Max Rady College of Medicine, Y3543 Bergen Cardiac Care Centre, University of
Manitoba, St. Boniface Hospital, Winnipeg, MB, Canada
Giuseppe Andò, MD, PhD Azienda Ospedaliera Universitaria Policlinico
“Gaetano Martino”, Department of Clinical and Experimental Medicine, University
of Messina, Messina, Italy
Shiva K. Annamalai, MD Department of Cardiovascular Disease, Tufts Medical
Center, Boston, MA, USA
Amer K. Ardati, MD MSc University of Illinois at Chicago, Department of
Internal Medicine, Chicago, IL, USA
Jaspreet S. Arora, MD Department of Interventional Cardiology, Kaiser
Permanente Los Angeles Medical Center, Cardiac Catheterization &
Electrophysiology Labs, Los Angeles, CA, USA
Vasilis Babaliaros, MD Emory University School of Medicine, Department of
Cardiology, Atlanta, GA, USA
Usman Baber, MD, MS Icahn School of Medicine at Mount Sinai, Cardiovascular
Institute, New York, NY, USA
Jehan Zahid Bahrainwala, MD Penn Presbyterian Medical Center,
Philadelphia, PA, USA

xv
xvi Contributors

Sripal Bangalore, MD, MHA Department of Medicine, Division of Cardiology

New York University Grossman School of Medicine, New York, NY, USA
Complex Coronary Interventions, Bellevue, Leon H. Charney Division of
Cardiology, New York University School of Medicine, New York, NY, USA
Abby Miriam Basalely, MD The Children’s Hospital at Montefiore, Nephrology
Division, Department of Pediatric Nephrology, Bronx, NY, USA
Sylvia Biso, MD University of Illinois at Chicago, Department of Internal
Medicine, Chicago, IL, USA
Somjot S. Brar, MD, MPH Kaiser Permanente Los Angeles Medical Center,
Cardiac Catheterization & Electrophysiology Labs, Regional Department of Cardiac
Catheterization, Los Angeles, CA, USA
Paolo Calabrò, MD, PhD Division of Clinical Cardiology, A.O.R.N. Sant’Anna e
San Sebastiano, Caserta, Italy
Department of Cardiothoracic and Respiratory Sciences, University of Campania
“Luigi Vanvitelli”, Naples, Italy
Michelle D. Carlson, MD Hennepin Healthcare, Cardiology Division,
Minneapolis, MN, USA
Rahul Chaudhary, MD, FACP Division of Hospital Internal Medicine,
Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
Ricardo J. Cigarroa, MD Cardiology Division, Department of Medicine,
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Justin M. Cloutier, MD, FRCPC University of Manitoba – St. Boniface Hospital,
Department of Cardiology, Y3039 Bergen Cardiac Care Centre, Winnipeg,
MB, Canada
Gates B. Colbert, MD Baylor University Medical Center, Internal Medicine,
Dallas, Department of Nephrology, Dallas, TX, USA
Jose F. Condado, MD, MS Emory University School of Medicine, Department of
Cardiology, Atlanta, GA, USA
Salvatore P. Costa Echocardiography Lab, Department of Cardiovascular
Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
Carlos D. Davila, MD Tufts Medical Center, Department of Cardiovascular
Disease, Boston, MA, USA
John F. Eidt, MD Baylor Scott & White Heart and Vascular Hospital, and Texas
A&M College of Medicine, Dallas, TX, USA
Sammy Elmariah, MD, MPH Cardiology Division, Department of Medicine,
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Contributors xvii

Michael James Ewing, MD, MS Baylor University Medical Center, Department

of Surgery, Dallas, TX, USA
Michael E. Farkouh, MD, MSc, FRCPC, FACC, FAHA Department of
Medicine, University of Toronto, Toronto General Hospital, Toronto, ON, Canada
Valerian Fernandes, MD, MRCP, FACC Department of Medicine, Division of
Cardiology, Medical University of South Carolina (MUSC) and Ralph H. Johnson
VA Medical Center, Charleston, SC, USA
Ladan Golestaneh, MD, MS Albert Einstein College of Medicine, Bronx, NY, USA
Felice Gragnano, MD Division of Clinical Cardiology, A.O.R.N. Sant’Anna e
San Sebastiano, Caserta, Italy
Department of Cardiothoracic and Respiratory Sciences, University of Campania
“Luigi Vanvitelli”, Naples, Italy
Gustavo Soares Guandalini, MD Cardiovascular Diseases Fellow, New York
University School of Medicine, Leon H. Charney Division of Cardiology, New
York, NY, USA
Angela L. Gucwa, MD Doctors Community Medical Center, Luminis Health,
Department of Surgery, Lanham, MD, USA
Paul A. Gurbel, MD Sinai Center for Thrombosis Research and Drug Development,
Sinai Hospital of Baltimore, Baltimore, MD, USA
Lena E. Jorde, BA Tufts Medical Center, Department of Cardiovascular Disease,
Boston, MA, USA
Ulrich P. Jorde, MD Department of Cardiology, Montefiore Medical Center, The
Bronx, NY, United States of America
Brandon Kai, MD Kaiser Permanente Los Angeles Medical Center, Cardiac
Catheterization & Electrophysiology Labs, Los Angeles, CA, USA
Sanjog Kalra, MD, MSc Einstein Medical Center Philadelphia,
Philadelphia, PA, USA
Navin K. Kapur, MD Tufts Medical Center, Department of Cardiovascular
Disease, Boston, MA, USA
Dimitri Karmpaliotis, MD, FACC, PhD Cardiovascular Research Foundation,
New York, NY, USA
NYPH/Columbia University Irving Medical Center, Center For Interventional
Vascular Therapy, New York, NY, USA
Archana Kedar, MBBS Cardiovascular Research Foundation, New York, NY, USA
NYPH/Columbia University Irving Medical Center, Center For Interventional
Vascular Therapy, New York, NY, USA
xviii Contributors

Ajay J. Kirtane, MD, SM, FACC, FSCAI Cardiovascular Research Foundation,

New York, NY, USA
NYPH/Columbia University Irving Medical Center, Center For Interventional
Vascular Therapy, New York, NY, USA
Márcio Galindo Kiuchi, MD, MSc, PhD Dobney Hypertension Centre, School of
Medicine - Royal Perth Hospital Unit, University of Western Australia, Perth, WA,
Australia
Paul Komenda, MD, FRCPC, MHA University of Manitoba, Research and
Home Hemodialysis, Seven Oaks Hospital, Chronic Disease Innovation Centre,
Winnipeg, MB, Canada
Nikoloz Koshkelashvili, MD Emory University School of Medicine, Department
of Cardiology, Atlanta, GA, USA
Amanda K. Leonberg-Yoo, MD, MS Renal Electrolyte and Hypertension
Division, Penn Presbyterian Medical Center, Philadelphia, PA, USA
Shawn X. Li Massachusetts General Hospital, New York Mount Sinai School of
Medicine, Boston, MA, USA
Hector M. Madariaga, MD Good Samaritan Medical Center, Department of
Medicine, Brockton, MA, USA
Roy O. Mathew, MD Department of Medicine, Division of Nephrology, University
of South Carolina School of Medicine, Columbia VA Health Care System,
Columbia, SC, USA
Peter A. McCullough, MD, MPH Baylor University Medical Center, Baylor
Heart and Vascular Hospital, Department of Internal Medicine, Texas A & M
College of Medicine, Division of Cardiology, Dallas, TX, USA
Jeffrey W. Moses, MD Cardiovascular Research Foundation, New York, NY, USA
NYPH/Columbia University Irving Medical Center, Center For Interventional
Vascular Therapy, New York, NY, USA
Debabrata Mukherjee, MD, MS Division of Cardiology, Department of Internal
Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
Harsha S. Nagarajarao, MD, FSCAI Division of Cardiology, Department of
Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
Nina Narasimhadevara, MD Division of Nephrology, University of Vermont
Medical Center, Department of Nephrology, Burlington, VT, USA
Elizabeth L. Nichols, PhD, MS The Dartmouth Institute of Health Policy and
Clinical Practice, Lebanon, NH, USA
Contributors xix

Chandra Ojha, MD, MRCP, FACC, FSCAI Division of Cardiology, Department

of Internal Medicine, Texas Tech University Health Sciences Center, El
Paso, TX, USA
Sahil A. Parikh, MD Division of Cardiology, Center for Interventional Vascular
Therapy, Columbia University Irving Medical Center, New York Presbyterian
Hospital, New York, NY, USA
Ami M. Patel, MD University of Maryland School of Medicine, Department of
Medicine, Division of Nephrology, Baltimore, MD, USA
Brijesh Patel, DO Department of Cardiology, West Virginia University Heart and
Vascular Institute, Morgantown, WV, United States of America
Shweta Punj, MD Northwestern University Feinberg School of Medicine,
Division of Nephrology and Hypertension, Chicago, IL, USA
Claudio Ronco, MD Nephrology, University of Padova, Padua, Italy
International Renal Research Institute of Vicenza, San Bortolo Hospital, Vicenza, Italy
Department of Medicine, University of Padova, Padua, Italy
Federico Ronco, MD Ospedale Dell’Angelo – AULSS3 Serenissima, Interventional
Cardiology, Department of Cardiac Thoracic and Vascular Sciences, Mestre -
Venezia, Italy
Amit Rout, MD Sinai Center for Thrombosis Research and Drug Development,
Sinai Hospital of Baltimore, Baltimore, MD, USA
Michael R. Rudnick, MD, FASN, FACP Perelman School of Medicine of the
University of Pennsylvania, Department of Nephrology, Penn Presbyterian Medical
Center, Philadelphia, PA, USA
Markus P. Schlaich, MD, PhD Dobney Hypertension Centre, School of Medicine -
Royal Perth Hospital Unit, University of Western Australia, Perth, WA, Australia
Departments of Cardiology and Nephrology, Royal Perth Hospital, Perth, WA,
Australia
Neurovascular Hypertension & Kidney Disease Laboratory and Human
Neurotransmitter Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne,
VIC, Australia
Sanjum S. Sethi, MD, MPH Division of Cardiology, Center for Interventional
Vascular Therapy, Columbia University Irving Medical Center, New York
Presbyterian Hospital, New York, NY, USA
Mahek Shah, MD Department of Cardiology, Thomas Jefferson University
Hospital, Philadelphia, PA, USA
xx Contributors

Gautam R. Shroff, MBBS, FACC Heart and Vascular Service Line, Division of
Cardiology, University of Minnesota Medical School, Hennepin Healthcare and
University of Minnesota, Department of Internal Medicine, Minneapolis, MN, USA
Mandeep S. Sidhu, MD Department of Medicine, Division of Cardiology, Albany
Medical College and Albany Medical Center, Albany, NY, USA
Richard Solomon, MD University of Vermont Medical Center, Department of
Nephrology, Larner College of Medicine, University of Vermont, Division of
Nephrology, Burlington, VT, USA
Tapati Stalam, MD University of Maryland Medical Center, Department of
Medicine, Baltimore, MD, USA
Harold M. Szerlip, MD Baylor University Medical Center, Dallas, Internal
Medicine, Division of Nephrology, Dallas, TX, USA
Udaya S. Tantry, PhD Sinai Center for Thrombosis Research and Drug
Development, Sinai Hospital of Baltimore, Baltimore, MD, USA
Beje Thomas, MD MedStar Georgetown University Hospital, Washington, DC, USA
Jennifer Tuazon, MD Northwestern University Feinberg School of Medicine,
Division of Nephrology and Hypertension, Chicago, IL, USA
Marco Valgimigli, MD, PhD Department of Cardiology, Bern University Hospital,
University of Bern, Bern, Switzerland
Stephani C. Wang, MD Department of Medicine, Albany Medical Center,
Albany, NY, USA
 Part I
Atherosclerotic Cardiovascular Disease
Burden in Chronic Kidney Disease
Chapter 1
The Burden of Coronary Artery Disease
in Chronic Kidney Disease

Sylvia Biso and Amer K. Ardati

Introduction

Cardiovascular disease (CVD) is the leading cause of death in the general US popu-
lation and in those with chronic kidney disease (CKD) [1, 2]. In patients with CKD,
cardiovascular death is more common than progression to end-stage renal disease
[3]. Cardiovascular death accounts for 40% of total mortality and among patients
on dialysis with acute myocardial infarction accounts for a quarter of all CVD
deaths [4].
CKD is an established independent risk factor for CVD and is widely consid-
ered a coronary artery disease (CAD) equivalent [5, 6]. Traditional risk factors are
more prevalent in CKD patients and are more challenging to control [7]. Non-
traditional risk factors like inflammation, oxidative stress, and coronary artery cal-
cification also have profound adverse associations in patients with CKD [8].
Cardiovascular outcomes improve after kidney transplantation; however, post-
transplant risk for adverse cardiac events remains higher compared to the general
population [9].
This chapter reviews trends in the prevalence of CVD in CKD, contributing risk
factors, and pathophysiology. We highlight studies and guidelines for prevention of
CVD in the CKD population.

S. Biso · A. K. Ardati (*)

University of Illinois at Chicago, Department of Internal Medicine, Chicago, IL, USA
e-mail: [email protected]

© Springer Nature Switzerland AG 2020 3

J. Rangaswami et al. (eds.), Kidney Disease in the Cardiac Catheterization
Laboratory, https://doi.org/10.1007/978-3-030-45414-2_1
4 S. Biso and A. K. Ardati

Epidemiology

Chronic Kidney Disease: A Major Health Burden

Chronic kidney disease (CKD) continues to be a major global health problem, with
the prevalence of CKD in the USA in 2011–2014 being around 14% [1]. Roughly
7.1% adults aged 20 and older are afflicted with CKD stages 1–2 and 6.4% with
CKD stages 3–5. These translate to 16 million and 14 million US adults who have
CKD stages 1–2 and 3–5, respectively [10]. According to the United States Renal
Data System in 2015, there were 703,243 cases of end-stage kidney disease (ESKD)
and 124,114 of these were newly-reported [11]. Between 1990 and 2014, the
Centers of Disease Control and Prevention – CKD surveillance program recorded
that ESKD cases had more than doubled [12]. There is also a high cost burden to the
healthcare system. In 2015, total Medicare expenditure for CKD and ESKD patients
was almost $100 billion dollars with one out of every five Medicare dollars being
spent on patients with CKD [11].

 revalence of Cardiovascular Disease in Patients with Chronic

P
Kidney Disease

Cardiovascular disease (CVD) is the most common cause of mortality in patients

with CKD (see Fig. 1.1) [2]. Compared to the 31.9% prevalence of CVD in patients

Cardiovascular deaths by CKD stage and albuminuria

45
Rate (number per 1000 patient-years)

41
40
35
30
25 24 24

20 19
15 13
11
10
6 10
5 5
0
Normal Microalbuminuria Macroalbuminuria

eGFR 15–59 eGFR 60–89 eGFR 90+

Fig. 1.1 The incidence of cardiovascular mortality from 1988 to 2000 among participants with
normal renal function, microalbuminuria, and macroalbuminuria. Albuminuria and kidney func-
tion correlate with cardiovascular mortality, although albuminuria appears to be more strongly
associated. (Adapted from Centers for Disease Control and Prevention. Chronic Kidney Disease
Surveillance System—United States website: http://www.cdc.gov/ckd)
1 The Burden of Coronary Artery Disease in Chronic Kidney Disease 5

without CKD, CVD occurs in 65.8% of patients with CKD aged 66 and older [1].
Younger patients with ESKD also exhibit a disproportionate burden of CVD [11]. A
study by Foster et al. determined that 13% of patients with CKD stages 1–2 and
29.6% of patients with CKD stages 3–5 experience CVD [10]. The most common
CVD conditions in patients with ESKD are coronary artery disease (CAD) and
heart failure (HF) both of which independently impact survival [11].

 hronic Kidney Disease as a Risk Factor and Predictor

C
of Coronary Artery Disease

Chronic kidney disease is an established risk factor for the occurrence of CAD [6].
Even mildly reduced estimated glomerular filtration rate (eGFR) (mean eGFR
78.5 ± 12.2 ml/min/1.73 m2) is associated with increased risk for CAD [13]. Cho
et al. assessed 4297 subjects with coronary CT angiography and determined that
early and asymptomatic CKD is already an independent risk factor for coronary
atherosclerosis [14]. Navaneethan, Schold, and Arrigain further observed that each
5 ml/min/1.73 m2 decline in eGFR is associated with higher risk of mortality sec-
ondary to CVD [2].
In addition to patients with CKD having high prevalence for significant CAD
[15], Gradaus et al. reported rapid progression for coronary atherosclerosis in dialy-
sis patients. Comparing coronary angiography at baseline and after a mean interval
of 30 months, 50% of dialysis patients developed hemodynamically significant new
stenoses of >50% of the luminal diameter [16]. CKD has also been shown to be an
independent predictor of cardiovascular events [17]. The 1-year risk of hospitaliza-
tions due to acute coronary syndrome (ACS) significantly increases as eGFR levels
decline. The 1-year ACS risk is 0.3%, 0.7%, 1.2%, 2.2%, and 1.6% for advancing
CKD stages with eGFR 60–89, 45–59, 30–44, 15–29, and <15 (not on dialysis),
respectively [18]. In addition to being an established risk factor and predictor of
CAD, advanced CKD is considered as a coronary artery disease equivalent [5].

Risk Factors and Pathophysiology

Traditional risk factors for the development of CVD as ascertained in the

Framingham Heart Study include dyslipidemia, hypertension, smoking, diabetes,
and obesity among others [19]. In the Choices for Healthy Outcomes in Caring for
ESRD (CHOICE) study, the prevalence of these atherosclerotic cardiovascular risk
factors (ASCVD) in dialysis patients was higher than non-dialysis participants
enrolled in the Third National Health and Nutrition Examination (NHANES III)
[20]. However, traditional risk factors cannot completely account for the increased
cardiovascular risk in patients with CKD. A pooled analysis of individuals from the
Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study
(CHS) revealed that the Framingham Equations under-predicted cardiovascular
events in patients with CKD at 5 and 10 years [21]. Non-traditional factors which
6 S. Biso and A. K. Ardati

Cardiovascular disease

Traditional risk factors Non - traditional risk factors

Dyslipidemia
Inflammatory milieu
Hypertension
Oxidative stress
Smoking
Vascular and valvular calcification
Obesity
Diabetes

Chronic kidney disease

Fig. 1.2 Traditional and non-traditional risk factors affecting CVD and CKD

are related to CKD and its pathophysiological derangements may explain this. Some
of these including inflammatory milieu, oxidative stress, coronary artery calcifica-
tion, and hyper homocysteinemia contribute to elevated cardiovascular risk and
worse outcomes in patients with CKD (see Fig. 1.2) [22].

Dyslipidemia

Dyslipidemia is an important cardiovascular risk factor for the general population.

The lipid profile phenotypes in CKD patients, however, are distinct from healthy
subjects with variations in lipoprotein classes that are dependent on eGFR [23].
Apolipoprotein (a) is elevated in CKD and is associated with coronary and carotid
artery disease [24, 25]. Besides the degree of elevation, there are also qualitative dif-
ferences in the lipoprotein behavior of CKD patients (e.g., oxidation and modifica-
tion of sdLDL) that make them more atherogenic [26]. Mutant forms of Apol1, one
of the apoproteins of HDL-C, have been found to be associated with rapid CKD and
ESKD progression [27]. This abnormality in lipoprotein profile accelerates athero-
sclerosis in CKD even at times when their absolute levels are not elevated [28, 29].

Hypertension

Hypertension (HTN) is the second leading cause of CKD and is the most common
cardiovascular comorbidity in patients with CKD [1]. Elevated blood pressure of
≥140/≥ 90 is present in >60% in patients with CKD in epidemiological surveys
[30]. In a study by Foster et al., hypertension is present in only 31.7% without CKD,
compared to 57.8% and 85.6% in patients with CKD stages 1–2 and 3–5, respec-
tively [10]. The presence of HTN in patients with CKD amplifies the risk of patients
1 The Burden of Coronary Artery Disease in Chronic Kidney Disease 7

for cardiovascular morbidity and mortality, particularly when patients also have
proteinuria [31]. In the Hypertension Detection and Follow-up Program, patients
with serum creatinine of 1.7 mg/dl or higher had a three-fold increased risk in 8-year
mortality compared to normal participants [32].

Smoking

Smoking has been significantly associated with elevated risk for end-stage kidney
disease in the Multiple Risk Factor Intervention (MRFIT) trial [33]. The Prevention
of Renal and Vascular Endstage Disease (PREVEND) trial found that smoking cor-
related to albuminuria and abnormal kidney function in non-diabetic patients
(Piento-Siesma) [34]. Even after adjusting for confounding factors, Cardiovascular
Health Study Cohort revealed that an increase in cigarette consumption was associ-
ated with worsening kidney function [35]. In a community-based study in Japan,
smoking was found to be a predictor of developing CKD [36]. Renal graft survival
in post-transplant patients has also been shown to be significantly worse in smokers
compared to non-smokers [37].

Inflammatory Milieu and Oxidative Stress

Inflammation and oxidative stress affect the cardiovascular system in several

ways. Elevated pro-inflammatory mediators (e.g., advanced glycation products)
in CKD result in vascular injury [38]. In this inflammatory environment, there
are stimuli for endothelial dysfunction resulting inproliferation of vascular
smooth muscle cells, [39] increased macrophage accumulation, vessel wall infil-
tration and adhesion with subsequent foam-cell formation, [40] and platelet acti-
vation [41]. These processes promote atherosclerotic plaque formation and
rupture.
Intrinsic characteristics of CKD patients (i.e., diabetes, hypertension, and
advanced age) predispose them to higher oxidative stress [42], they have
increased pro-inflammatory mediators with declining renal function [43], and
they have defects in their anti-oxidant systems [44]. The dialysis procedure itself
can activate complement pathways and circulating neutrophils when blood
comes in contact with dialysis membranes. In addition, transfer of endotoxins
from dialysate to the blood is a potent trigger for production of reactive oxygen
species and activation of leukocytes [45]. Impaired nitric oxide synthesis in
CKD patients is also a possible mechanism for endothelial dysfunction [46].
Various uremia metabolites (e.g., asymmetric dimethylarginine and p-cresylsul-
fate) have been associated with accelerated atherogenesis and cardiovascular
events [47, 48].
8 S. Biso and A. K. Ardati

Coronary Artery Calcification

Coronary artery calcification (CAC) is more common in patients with declining

renal function. CAC is prevalent in young adults with ESKD. Goodman et al. found
that among patients 20–30 years of age with ESKD, 87.5% had coronary artery
calcification (CAC) (CAC scores 1157 ± 1996) compared to their normal counter-
parts where only 5% had coronary calcification (peak CAC score of 77) [49]. The
occurrence of CAC varies with CKD stage. It is present in 13.9% of patients with
CKD stages I and II and up to 83% in patients with CKD stages III–V [50].
Worsening renal function also correlates with higher calcium scores. The Dallas
Heart Study showed that CAC scores of 400 were twice the rate in patients with
CKD stages 1–2 (3.5%) and nine times higher in patients with CKD stages 3–5
(16%) when compared to normal participants (1.7%). This association was found to
be significantly stronger in diabetic patients [51].
Vascular calcification is important because of its close relationship with cardio-
vascular morbidity and mortality in this subset of patients [52]. Vascular smooth
muscle cells in CKD patients, likely induced by uremia, differentiate into osteoblast-­
like cells initiating tissue mineralization process [53]. This vascular calcification
has deleterious hemodynamic consequences such as reduced coronary microcircu-
lation, increased arterial stiffness, and increase in left ventricular hypertrophy [54].
A study by Shimoyama, Tsuruta, and Niwa showed that dialysis patients with CAC
scores of 0–105, 110–1067, and >1094 have all-cause mortality of 7.6%, 43.3%,
and 52.2%, respectively. The cardiovascular mortality in these groups were 3%,
22.4%, and 26.9%, respectively. CAC was, thus, found to be an independent predic-
tor of cardiovascular events in CKD patients [55].

Risk Factor Control

Lifestyle Interventions

Obesity is an independent risk factor for the advancement of CKD [56]. Weight loss
has been shown to remarkably reduce proteinuria and blood pressure [57]. The
impact of weight loss was particularly seen in diabetic patients, in those with meta-
bolic syndrome, and after bariatric surgery [58]. A multidisciplinary program
including diet, exercise, and pharmacotherapy with orlistat showed significant body
weight reduction and improved functional ability in obese CKD patients (see
Fig. 1.3) [59]. In patients with BMI of 40 kg/m2 or greater in the general population,
however, bariatric surgery is considered more effective than nonsurgical treatment
in achieving long-lasting weight loss and improvement in comorbid conditions [60].
A concern in CKD patients is use of weight loss medications as these are generally
unsafe in patients with eGFR <60 ml/min/1.73 m2 [61]. An exception is Orlistat
which has only modest efficacy [62].
1 The Burden of Coronary Artery Disease in Chronic Kidney Disease 9

Fig. 1.3 Risk factor

• Weight loss • Statins
modification for patients
• Physical
with CKD
activity

Addressing Lipid
obesity control

Blood
Smoking pressure
cessation control
• Counselling • Anti-
• Nicotine hypertensives
replacement

Physical inactivity is an independent predictor of CVD morbidity and mortality

in the general population [63] and patients with CKD [64]. Regular exercise of
30 min or longer three times a week improved aerobic capacity, blood pressure,
muscle strength, and quality of life in CKD, dialysis, and renal transplant patients
[65]. Current recommendations in adults with CKD include starting them on low-­
intensity resistance and aerobic exercise with slow progression as tolerated to pre-
vent discontinuation of exercise. Strength-training interventions may be more
appropriate for weak patients [66]. Identifying barriers to exercise, exercise assess-
ment, counselling, and training may benefit patients with CKD.

Smoking Cessation

There are studies that show that smoking cessation has beneficial effects on the
kidneys and slows the rate of decline of kidney function. Chase et al. reported that
when patients ceased smoking, albumin excretion significantly improved [67].
Sawicki et al. observed that there is reduced progression of CKD in non-smokers
(11%) than in patients who were ex-smokers (33%) and active smokers (53%) [68].
Furthermore, better graft survival was found in patients who stopped smoking prior
to kidney transplant compared to those who continued to do so [69].

Lipid Control

For the treatment of dyslipidemia, statins [3-hydroxy-3-methylglutaryl-coenzyme

(HMG-CoA) reductase inhibitors] have been shown to have cardio-protective effects in
CKD stages 1–4. In the Cholesterol and Recurrent Events (CARE) study, a subgroup
10 S. Biso and A. K. Ardati

of 1711 patients who had creatinine clearances of <75 ml/min (mean creatinine clear-
ance of 61 ml/min) showed that pravastatin therapy was associated with an almost 30%
reduction in major coronary events or cardiovascular deaths in patients with mild CKD
[70]. In another study, the Pravastatin Pooling Project, pravastatin was shown to signifi-
cantly decrease cardiovascular mortality and morbidity (hazard ratio 0.77) with abso-
lute risk reduction of 6% in patients with moderate CKD [71]. In the Study of Heart and
Renal Protection (SHARP) trial, the simvastatin and ezetimibe group had 17% reduc-
tion in myocardial infarction or cardiovascular deaths compared to placebo [72].
Although the cardiovascular benefits of statins are well-established in patients
with CKD stages 1–4, this is not the case for patients on maintenance dialysis. In the
Die Deutsche Diabetes Dialyse (4D) study, 1255 diabetic patients on dialysis received
atorvastatin 20 mg or placebo for a median follow-up period of 4 years. The patients
on the atorvastatin group’s low-density lipoprotein (LDL) cholesterol dropped by
42% compared to 1.4% in the placebo group. However, atorvastatin did not statisti-
cally significantly reduce nonfatal myocardial infarction, cardiovascular death, and
stroke in diabetic patients receiving dialysis [73]. Similarly, in the Study to Evaluate
the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of
Survival and Cardiovascular Events (AURORA), rosuvastatin lowered LDL choles-
terol level, but did not have any significant impact on myocardial infarction and car-
diovascular death [74]. Because there is no direct evidence that statins improve
cardiovascular outcomes in dialysis patients, the current Kidney Disease: Improving
Global Outcomes (KDIGO) lipid guidelines recommend not initiating statins in dial-
ysis patients. If a patient is already on a statin medication at the initiation of dialysis,
it may either be continued or stopped [75]. Further data are necessary to determine if
initiation/continuation of statins are beneficial in selective populations such as those
transitioning to dialysis initiation, patients with failed kidney allografts returning to
dialysis, and those on frequent/prolonged dialysis prescriptions.

Hypertension Control

CKD may cause hypertension and hypertension itself can cause worsening of renal
function [66]. According to the NHANES statistics (1999–2014), blood pressure
awareness, treatment, and control among CKD patients were at 72.2%, 52.8%, and
67.4%, respectively [76]. Adequate blood pressure control is even lower in a study
by Foster et al. with only 42% and 44% of patients with CKD stages 1–2 and 3–5,
respectively, being satisfactorily treated [10]. This is despite robust literature on the
adverse cardiovascular impact of hypertension in patients with CKD.
Blood pressure goals for CKD patients have been dynamic through the years and
recommendations regarding treating hypertension in CKD patients are still evolv-
ing. In the Systolic Blood Pressure Intervention Trial (SPRINT), it has been shown
that intensive blood pressure control to a systolic blood pressure target of less than
120 mmHg, as compared to the previous target of 140 mmHg, in patients with
CKD, resulted in reduced cardiovascular events. Patients in the intensive treatment
group had significantly fewer rates of acute coronary syndrome, acute heart failure,
1 The Burden of Coronary Artery Disease in Chronic Kidney Disease 11

and cardiovascular deaths [77]. Close to a third of subjects in SPRINT had baseline
CKD, and the benefits of intensive blood pressure control were also reported sepa-
rately in the subset of patients with baseline CKD [78]. However, another sub- anal-
ysis of SPRINT reported a higher rate of incident CKD in subjects without CKD at
baseline during enrollment, but the cardiovascular adverse event rate reduction out-
weighed the risk for incident CKD events [79]. Finally, a recent analysis of the CKD
subset of SPRINT demonstrated no differences in the rates of renal tubular bio-
marker levels between the intensive and standard BP groups, thus making a case for
the eGFR fluctuations noted with intensive BP control more likely to be related to
hemodynamic changes that are intrinsically reversible as opposed to progression of
intrinsic CKD, per se [80]. The American College of Cardiology and American
Heart Association Task Force (ACC/AHA) recently released blood pressure man-
agement guidelines recommending a blood pressure threshold of ≥130/80 mmHg
for initiation of antihypertensive treatment in CKD patients as they have elevated
risk for developing cardiovascular disease. ACE inhibitors (or ARBs, if ACE inhibi-
tors are not tolerated) are recommended for patients with albuminuria (≥300 mg/g
creatinine), otherwise, any first-line anti-hypertensive medication is acceptable [81].
Blood pressure control in patients with ESKD on dialysis is more complicated
and poses inherent challenges. For this subset of patients, studies have described
elevated risk of mortality with very low blood pressure [82]. Symptomatic intradia-
lytic hypotension is also more frequent in centers that have better target blood pres-
sures achieved post-dialysis [83]. This can be attributed to volume shifts during
dialysis that ESKD patients cannot adequately respond to because of insufficient
sympathetic response and increased arterial stiffness resulting in poor vascular com-
pliance [84]. Mazzuchi, Carbonell, and Fernandez-Cean found that late mortality
(death at ≥5 years of HD) is significantly associated with hypertension. In addition,
several meta-analyses showed that anti-hypertensive therapy in dialysis patients sig-
nificantly decreases cardiovascular events and mortality by as much as 30% [85, 86].
This highlights the importance of blood pressure control in dialysis patients. Given
the challenges with balancing intra-dialytic hypotension and the need to achieve tar-
get optimal “dry weights “in subjects on dialysis, encouraging the use of frequent or
prolonged dialytic therapies may help achieve tight blood pressure control without
sacrificing quality of life and symptoms of hypoperfusion in patients with ESKD [87].

 utcomes and Prognosis of Coronary Artery Disease

O
in Chronic Kidney Disease

 ardiovascular Outcomes for CKD After Acute

C
Myocardial Infarction

Outcomes after adverse cardiovascular events are worse in patients with CKD and
ESKD. For CKD patients without diabetes mellitus (DM) or overt CVD, the mortal-
ity rate is 50 deaths per 1000 patient-years. CKD patients with both DM and CVD
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