Table of contents : Preface Contents 1: Implications of Chronic Kidney Disease on the Epidemiology of Cardiovascular Disease 1.1 Introduction 1.2 Cardiovascular Risk in Chronic Kidney Disease 1.3 Coronary Heart Disease 1.4 Heart Failure 1.5 Valvular Calcific Deposits and Complications 1.6 Arrhythmias 1.7 Summary References 2: Prevalence and Progression of Cardiovascular Calcification in the General Population and Patients with Chronic Kidney Disease 2.1 Coronary Artery Calcium as a Marker of Atherosclerotic Vascular Disease in the General Population 2.2 Cardiovascular Calcification in Chronic Kidney Disease 2.2.1 Pathogenesis 2.2.2 Epidemiology and Clinical Significance of Cardiovascular Calcification in CKD 2.2.3 Progression of Cardiovascular Calcification in CKD 2.3 Conclusions References 3: Spectrum of Ventricular Dysfunction in Chronic Kidney Disease References 4: The Myocardium in Renal Failure References 5: Impact of Renal Failure on Valvular Heart Disease 5.1 Introduction 5.2 Pathology 5.3 Prevention 5.4 Diagnosis and Follow Up 5.5 Treatment 5.5.1 Aortic Valve Stenosis 5.5.2 Aortic Regurgitation 5.5.3 Mitral Valve Stenosis 5.5.4 Mitral Regurgitation 5.6 Choice of Valve Type 5.7 Management Post-Surgery: Anticoagulation 5.8 Conclusions References 6: Arrythmias in Chronic Kidney Disease: Working Towards a Clinical Approach in Atrial Fibrillation 6.1 Introduction 6.2 CKD, Atrial Fibrillation, and Stroke 6.3 Anticoagulation in Atrial Fibrillation and CKD: Shifting Paradigms to Novel Anticoagulants 6.3.1 NOACs Versus Warfarin 6.3.2 Individual NOACs and Post-Hoc Analyses 6.3.3 Network Meta-Analyses 6.3.4 Post-Marketing Observational Surveillance Studies 6.4 Working Towards a Clinical Approach to Stroke Prevention CKD and Atrial Fibrillation 6.5 Conclusion References 7: Type 1 Cardio-Renal Syndrome 7.1 Introduction 7.2 Definition of Acute (Type 1) Cardio-Renal Syndrome 7.3 Factors Contributing to the Development of Acute CRS 7.4 Preventing Type 1 CRS: Identifying Sub-Clinical Cardio-Renal Injury 7.5 Managing Type 1 CRS 7.6 Conclusions References 8: Type 2 Cardiorenal Syndrome 8.1 Introduction 8.2 Description of CRS2 8.3 Pathophysiology 8.4 Chronic Inflammatory State: Fibrosis as the Unifying Pathogenesis 8.5 Cardiorenal Type 2 in Heart Failure with Preserved Ejection Fraction 8.6 Diagnosis 8.6.1 Biomarkers and CRS2 8.6.1.1 Cardiac Biomarkers 8.6.1.2 Renal Biomarkers GFR and Albuminuria 8.6.2 Cystatin C 8.6.3 Potential Therapies 8.6.3.1 Angiotensin-Converting Enzyme (ACE) Inhibitor and an Angiotensin Receptor Blocker 8.6.3.2 Mineralocorticoid Receptor Antagonists 8.6.3.3 Angiotensin Receptor Neprilysin Inhibitor 8.7 Newer Options for Diabetics: Sodium–Glucose Cotransporter 2 Inhibitors and Glucagon-Like Peptide-1 Agonist 8.7.1 Cardiac Devices 8.7.1.1 CRT 8.7.1.2 LVAD 8.8 Conclusion References 9: Type 3 Cardiorenal Syndrome 9.1 Introduction 9.2 Epidemiology of AKI 9.3 Epidemiology of Renocardiac Syndrome 9.4 Diagnosis of AKI 9.5 Pathophysiology of Renocardiac Syndrome 9.5.1 Hemodynamic Factors 9.5.2 Non-hemodynamic Factors 9.6 Endothelial Dysfunction 9.7 Management: Cardiac Related 9.7.1 Diuretics 9.7.2 Vasodilators 9.7.3 Natriuretic Peptides 9.7.4 Mechanical Ultrafiltration and Dialysis 9.8 Prevention of CRS-3 References 10: Type-5 Cardiorenal Syndrome 10.1 Introduction 10.2 Pathogenesis of CRS 5 10.2.1 CRS-5 and Sepsis 10.2.2 CRS-5 and Amyloidosis 10.2.3 CRS-5 and Systemic Lupus Erythematosus (SLE) 10.2.4 CRS-5 and Fabry’s Disease 10.2.4.1 Pathology of Renal Involvement 10.2.4.2 Clinical Renal Involvement 10.2.4.3 Pathology of Cardiac Involvement 10.2.4.4 Clinical Cardiac Involvement 10.3 Diagnosis of CRS-5 10.4 Management of CRS-5 References 11: Post Contrast Acute Kidney Injury 11.1 Introduction 11.2 Name 11.3 Definition 11.4 Pathophysiology 11.4.1 In Vitro 11.4.2 In Vivo 11.4.3 Man 11.5 Epidemiology and Risk 11.6 Complications 11.7 Prevention 11.7.1 More Fluid Rather than Less Is Beneficial [43–46] 11.7.2 Oral Fluid Intake May Be Very Important 11.7.3 Increasing Urine Output May Be the Key to a Successful Prophylactic Strategy 11.8 Controversies 11.9 Conclusion References 12: Distinct Cardiorenal Syndromes: Cardiac Surgery Associated Acute Kidney Injury 12.1 Introduction and Epidemiology 12.2 Risk Factors for CSA-AKI 12.2.1 Patient Specific Factors 12.2.2 Surgical Factors 12.2.3 Risk Scores 12.3 The Role of Novel Biomarkers in the Diagnosis of CSA-AKI 12.3.1 Neutrophil Gelatinase-Associated Lipocalin 12.3.2 Cystatin C 12.3.3 IL-18 12.3.4 Kidney Injury Molecule-1 12.4 Pathophysiology of CSA-AKI 12.4.1 Inflammatory Response 12.4.2 Renal Ischemia 12.4.3 Nephrotoxic Medications 12.4.4 Factors Unique to Cardiopulmonary Bypass 12.4.4.1 Hemolysis 12.4.4.2 Embolism 12.4.4.3 Temperature Control 12.5 Treatment and Prevention 12.5.1 Risk Factor Modification 12.5.2 Pharmacologic Interventions 12.5.2.1 Natriuretic Peptides 12.5.2.2 Fenoldepam 12.5.2.3 Dexmetodomidine 12.5.2.4 Levosimendan 12.5.2.5 N-Acetylcysteine 12.5.2.6 Sodium Bicarbonate 12.5.2.7 Statins 12.5.3 Remote Ischemic Preconditioning 12.5.4 Renal Replacement Therapy 12.6 Pediatrics 12.7 Summary and Future Directions References 13: Pediatric Cardiorenal Syndromes 13.1 Introduction 13.2 CRS Type 1: Acute Cardiorenal Syndrome 13.3 CRS Type 2: Chronic Cardiorenal Syndrome References 14: Key Concepts of Organ-Crosstalk 14.1 Background 14.2 Gene Expression 14.3 Epigenetic and Epigenome 14.4 Small Non-coding RNAs 14.5 Extracellular Vesicles 14.6 Proteomics and Metabolomics 14.7 Inflammation 14.8 Immune Cell Signaling and Immunomodulation: The Role of Innate and Adaptive Immunity 14.9 Neurohormonal Systems in Cardiorenal Syndromes 14.10 Endocrine Dysregulation in Cardiorenal Syndromes References 15: Methods to Assess Intra- and Extravascular Volume Status in Heart Failure Patients 15.1 Introduction 15.2 Pathophysiology of Fluid Overload in Heart Failure 15.3 Blood Volume Measurement and the Indicator Dilution Principle 15.4 Bio-electrical Impedance Analysis Methods 15.4.1 Bio-electrical Impedance Vector Analysis 15.4.2 Impedance Cardiography 15.4.3 Bioimpedance Spectroscopy 15.4.4 Bioreactance 15.5 Other Methods for Non-invasive Hemodynamic Monitoring 15.6 Less Invasive Hemodynamic Monitoring Methods 15.6.1 Cardiac Output Monitoring by Pulse Contour Analysis 15.6.2 Peripheral Intravenous Volume Analysis 15.7 Hemodynamic Data from Implanted Monitors 15.7.1 Pulmonary Artery Pressure Sensors 15.7.2 Left Atrial Pressure Sensors 15.8 Data from Cardiac Implanted Electronic Devices 15.9 Ultrasound Methods 15.9.1 Lung Ultrasound 15.9.2 Inferior Vena Cava Ultrasound 15.10 Biomarkers 15.11 Prospective and Conclusions References 16: Novel Biomarkers of Acute Cardiorenal Disease 16.1 Brief Terminology of Acute Cardiorenal Disease 16.2 Major Pathomechanisms of Cardiorenal Syndromes (CRS) Types 1 and 3 16.3 Biomarkers of Acute Cardiorenal Disease 16.3.1 Biomarkers for Early AKI Detection After Cardiac Impairment (CRS Type 1) 16.3.1.1 Biomarkers of Glomerular Filtration Serum Cystatin C Determination of Renal Function and Injury Using Near-Infrared Fluorimetry in CRS 16.3.1.2 Biomarkers of Acute Renal Tubular Damage/Stress 16.3.1.3 Biomarkers of Acute Renal Tubular Damage/Stress After ADHF/ACS Angiotensinogen KIM-1 L-FABP NGAL: Biological Characteristics NGAL: Clinical Trials Proenkephalin TIMP-2/IGFBP7 Biomarker Combinations Interpretation of Test Results of Markers of Acute Tubular Damage/Stress 16.3.2 Markers to Predict or Indicate Cardiac Impairment After AKI (CRS type 3) 16.3.2.1 Novel Kidney Biomarkers for Early Diagnosis of Diuretic Resistance 16.3.2.2 Novel Kidney Biomarkers for Early Diagnosis of Cardiac Impairment 16.3.2.3 Novel Cardiac Biomarkers of Plaque Destabilization Before Troponin Rise 16.3.2.4 Novel Biomarkers of Cardiac Dysfunction 16.4 Summary References 17: Novel Biomarkers of Chronic Cardiorenal Disease 17.1 Conclusions References 18: Mechanisms of Kidney and Heart Cross-talk in Acute Kidney Injury 18.1 Introduction 18.2 Acute Renocardiac Syndrome 18.3 Mechanisms of Cardiac Injury Triggered by AKI 18.4 Possible Interventions Against Cardiac Injury in AKI 18.5 Long Term Prognosis of Acute Renocardiac Syndrome 18.6 Conclusion References 19: Kidney and the Heart in Multiorgan System Failure 19.1 Introduction 19.2 Fluid Balance and Kidney and Heart Interaction 19.3 Hemodynamics 19.4 Hemodynamic Targets 19.5 Afterload Therapy: Afterload Reduction and Treatment of Vasoplegia 19.6 Contractility 19.7 Position on the Ventricular Function Curve: Volume Responsiveness 19.8 Ventricular Compliance 19.9 Ventricular Imaging 19.10 Oxygen Delivery and Balance 19.11 Whole Body Perfusion Monitoring 19.12 Specific Organ Perfusion 19.13 Kidney Perfusion: Acute Kidney Injury and Acute Kidney Stress 19.14 Summary References 20: Cardiac Consequences of Renal Artery Stenosis 20.1 Introduction 20.2 Prevalence 20.3 Pathophysiology 20.4 RAS and Cardiovascular Disease 20.5 Clinical Manifestations 20.6 Diagnosis 20.7 Medical Treatment 20.8 Renal Revascularization 20.9 Important Clinical Trials 20.10 Guidelines Summary 20.11 Conclusion References 21: Obesity 21.1 Introduction 21.2 Obesity Related Dysfunction of Cardio-Renal Axis and Cardiac Adaptation 21.3 Renal Adaptations to Obesity 21.4 Role of Cytokines, Inflammatory Pathways, and Adipokines in Obesity 21.5 Role of Aldosterone and Resistin 21.6 Obesity, Metabolic Status and Chronic Kidney Disease 21.7 Therapeutic Interventions 21.7.1 Dietary Modification 21.7.2 Physical Activity 21.7.3 Behavioral Modification 21.7.4 Antiobesity Agents 21.8 Obstructive Sleep Apnea (OSA) 21.9 Hypertension Pharmacotherapy 21.10 Bariatric Surgery 21.11 Conclusion References 22: Class Effects of SGLT2 Inhibitors on Cardiorenal Outcomes 22.1 The EMPA-REG OUTCOME Trial 22.2 The CANVAS Program 22.3 The DECLARE-TIMI 58 Trial 22.4 The CREDENCE Trial 22.5 Cardiovascular and Renal Outcomes 22.6 Outcome Definitions 22.7 Other Notable Trial Results 22.8 RAASi Use 22.9 Safety 22.10 Future Potential Benefits of SGLT2i 22.11 Class Effects 22.12 Conclusions References 23: Management of Diabetes Mellitus in Acute and Chronic Cardiorenal Syndromes 23.1 Introduction 23.2 Screening for Diabetes 23.3 Screening for CKD 23.4 Medications in Diabetic Nephropathy 23.4.1 Insulin 23.4.1.1 Long-Acting Insulins 23.4.1.2 Intermediate-Acting Insulin 23.4.1.3 Short-Acting Insulin 23.4.1.4 Rapid-Acting Insulins 23.4.1.5 Premixed Insulins 23.4.1.6 Varying Insulin Concentrations 23.4.1.7 Inhaled Insulin 23.4.2 Oral Medications 23.4.2.1 Metformin (Biguanides) 23.4.2.2 Sulfonylureas 23.4.2.3 Glinides 23.4.2.4 Thiazolidinediones 23.4.2.5 Alpha-Glucosidase Inhibitors 23.4.2.6 Dipeptidyl Peptidase-4 Inhibitors 23.4.2.7 Sodium-Glucose Co-transporter 2 (SGLT2) Inhibitors 23.4.2.8 Other Oral Medications 23.4.3 Other Subcutaneous Medications 23.4.3.1 GLP-1 Receptor Agonists 23.4.3.2 Amylin Analog 23.5 Glycemic Control 23.5.1 Glycemic Goal Targeting an A1c ~7.0% 23.5.2 A1c and Glucose Targets 23.5.3 Accuracy of A1c 23.5.4 Strategy for Glycemic Control in Type 1 and type 2 Diabetes 23.5.4.1 Type 1 DM 23.5.4.2 Type 2 DM 23.5.4.3 Patients on Dialysis 23.6 Cardiovascular Disease and Risk Factors 23.6.1 Blood Pressure Control 23.6.2 Dyslipidemia 23.6.3 Nutrition and Dietary Protein 23.7 Referral to Specialized Care 23.8 Conclusion References 24: Pharmacoepidemiology in Cardiorenal Medicine 24.1 Introduction 24.2 Therapies and Adaptations 24.2.1 Angiotensin Converting Enzyme Inhibitors 24.2.2 Angiotensin Receptor Blockers 24.2.3 Beta Adrenergic Receptor Blockers 24.2.4 Mineralocorticoid Receptor Antagonists 24.2.5 Diuretics 24.2.6 Statins 24.2.7 Digoxin 24.2.8 Sodium-Glucose Transport Protein 2 Inhibitors 24.3 Medication Usage Limitations 24.3.1 Pill Burden 24.3.2 Poor Communication and Affordability 24.3.3 Side Effects 24.3.4 Contextual Issues 24.4 Conclusion References 25: Anticoagulation for Atrial Fibrillation in Advanced Chronic Kidney Disease 25.1 Vitamin K Antagonists in Patients with Advanced Chronic Kidney Disease and End Stage Renal Disease 25.2 DOACs in Patients with Advanced CKD and ESRD 25.3 Percutaneous Left Atrial Appendage Occlusion References 26: Cardiac Consultative Approach to Hemodialysis Patients and Cardiovascular Evaluation and Management of Potential Kidney Transplant Recipients 26.1 Evaluation and Management of Dialysis-Dependent Chronic Kidney Disease Prior to Renal Transplant and Non-cardiac Surgery 26.2 Challenges in the Evaluation of Patients with Advanced Chronic Kidney Disease and End-Stage Renal Disease for Renal Transplant 26.3 Preoperative Factors 26.3.1 Chronic Conditions 26.3.2 Acute and Recent Events 26.3.3 Intraoperative and Postoperative Events 26.4 Assessment and Management of Potential Renal Transplant Recipients 26.5 Risk Stratification and Detection of Cardiovascular Disease in Patients Undergoing Pre-renal-Transplant Evaluation 26.5.1 Very High Risk 26.5.2 High Risk 26.5.3 Moderate Risk 26.5.4 Low Risk 26.6 Risk Assessment Methods 26.6.1 Risk Estimation Indices 26.6.2 Noninvasive Imaging Studies 26.6.3 Cardiopulmonary Stress Testing 26.6.4 Biomarkers 26.6.5 Invasive Coronary Angiogram 26.6.6 Approach to Screening Potential Renal Transplant Candidates 26.7 Surveillance and Perioperative Management 26.8 Revascularization in Dialysis-Dependent ESRD Patients 26.9 Revascularization in Acute Coronary Syndrome 26.10 Revascularization in Stable Coronary Artery Disease 26.11 Cardiac Surgery in Dialysis-Dependent CKD References 27: Nephrology Inpatient Consultative Approach in Patients with Cardiovascular Disease 27.1 Introduction 27.2 Consultative Approach to the Patient with Acute Heart Failure and Diuretic Resistance 27.2.1 Pathophysiological Considerations in Acute Heart Failure 27.2.2 Determinants of Renal Perfusion in Acute Heart Failure 27.2.3 Diuretic Resistance: Mechanisms and Clinical Approach in Worsening Renal Function with Acute Heart failure 27.2.4 Ultrafiltration for Decongestion in Acute Heart Failure: Is There a Role in Contemporary Cardio-Renal Medicine? 27.2.5 Optimization Prior to Cardiac Catheterization and Cardiac Surgery: Role of the Nephrologist 27.2.6 Reduction of Contrast Induced Acute Kidney Injury 27.2.7 Reduction of Acute Kidney Injury After Cardiovascular Interventions: Procedural Aspects 27.2.8 Reduction of Acute Kidney Injury After Cardiovascular Interventions: Targeting Renal Blood Flow and Filtration Fraction 27.2.9 Pre-procedural Medical Optimization of Patients with Advanced Chronic Kidney Disease 27.3 Continuous Renal Replacement Therapy for Severe Acute Kidney Injury 27.4 Conclusions and Future Directions References Index