Endocrine Disorders in Kidney Disease: Diagnosis and Treatment [1st ed.] 978-3-319-97763-8, 978-3-319-97765-2

Table of contents :
Front Matter ....Pages i-xiv
Front Matter ....Pages 1-1
Insulin Resistance and the Metabolic Syndrome in Kidney Disease (e.g., the Cardiorenal Metabolic Syndrome) (Vikram Patney, Sivakumar Ardhanari, Adam Whaley-Connell)....Pages 3-13
Diabetic Kidney Disease (Robert C. Stanton)....Pages 15-25
Glucose Homeostasis and the Burnt-Out Diabetes Phenomenon in Patients with Kidney Disease (Masanori Abe, Csaba P. Kovesdy, Kamyar Kalantar-Zadeh)....Pages 27-38
Glycemic Metrics and Targets in Kidney Disease (Joshua J. Neumiller, Irl B. Hirsch)....Pages 39-48
Diabetic Pharmacotherapies in Kidney Disease (Deborah A. Chon, Rachael T. Oxman, Rashmi S. Mullur, Jane Eileen Weinreb)....Pages 49-74
Diabetes Mellitus and Renal Transplantation (Curtiss B. Cook, Harini Chakkera)....Pages 75-81
Front Matter ....Pages 83-83
Evaluating Thyroid Function Tests in Patients with Kidney Disease (Stephanie Smooke Praw, Jennifer Sue An Way, Rebecca Weiss)....Pages 85-96
Thyroid Status and Outcomes in Kidney Disease (Connie M. Rhee, Gregory A. Brent, Kamyar Kalantar-Zadeh)....Pages 97-109
Front Matter ....Pages 111-111
Testosterone Deficiency and Other Testicular Disorders in Kidney Disease (Anna L. Goldman, Shalender Bhasin)....Pages 113-125
Amenorrhea and Estrogen Disorders in Women with Kidney Disease (Kavitha Vellanki, Holly Kramer)....Pages 127-138
Pregnancy in Kidney Disease (Madeleine V. Pahl)....Pages 139-150
Front Matter ....Pages 151-151
Lipid Disorders Associated with Chronic Kidney Disease and Nephrotic Syndrome (Hamid Moradi, Nosratola D. Vaziri)....Pages 153-169
Drugs for Treatment of Dyslipidemia Available in the USA (Elani Streja, Dan A. Streja)....Pages 171-195
Front Matter ....Pages 197-197
Calcium Homeostasis in Kidney Disease (Michel Chonchol, Jessica Kendrick)....Pages 199-206
Phosphorus Retention and Elevated FGF-23 in Chronic Kidney Disease (Yoshitsugu Obi, Connie M. Rhee)....Pages 207-221
Vitamin D and Parathyroid Hormone in Kidney Disease (Sagar U. Nigwekar)....Pages 223-229
Management of Bone Disorders in Kidney Disease (Stuart M. Sprague)....Pages 231-242
Mineral and Bone Disorders Following Renal Transplantation (Hatem Amer, Rajiv Kumar)....Pages 243-261
Front Matter ....Pages 263-263
Obesity in Kidney Disease (Peter Stenvinkel)....Pages 265-275
Adiponectin and Leptin in Kidney Disease Patients (Jerry Zhong Yu, Kamyar Kalantar-Zadeh, Connie M. Rhee)....Pages 277-290
Front Matter ....Pages 291-291
Growth Hormone Disorders and Abnormal Stature in Kidney Disease (Amira Al-Uzri, Annabelle N. Chua, Bradley A. Warady)....Pages 293-307
Other Pituitary Disorders and Kidney Disease (Wenyu Huang, Mark E. Molitch)....Pages 309-320
Endocrine System in Acute Kidney Injury (Alice Sabatino, Graziano Ceresini, Michela Marina, Enrico Fiaccadori)....Pages 321-331
Nutrition and Endocrine Disorders in Kidney Disease (Anuja Shah, Joel Kopple)....Pages 333-345
Back Matter ....Pages 347-354

Citation preview

Endocrine Disorders in Kidney Disease Diagnosis and Treatment Connie M. Rhee Kamyar Kalantar-Zadeh Gregory A. Brent  Editors

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Endocrine Disorders in Kidney Disease

Connie M. Rhee Kamyar Kalantar-Zadeh Gregory A. Brent Editors

Endocrine Disorders in Kidney Disease Diagnosis and Treatment

Editors Connie M. Rhee Division of Nephrology and Hypertension Departments of Medicine and Public Health University of California Irvine School of Medicine Orange, CA USA Gregory A. Brent Division of Endocrinology, Diabetes, and Hypertension Departments of Medicine and Physiology David Geffen School of Medicine at UCLA Los Angeles, CA USA

Kamyar Kalantar-Zadeh Division of Nephrology and Hypertension Departments of Medicine, Pediatrics, Public Health, and Nursing Sciences University of California Irvine School of Medicine Orange, CA USA

ISBN 978-3-319-97763-8    ISBN 978-3-319-97765-2 (eBook) https://doi.org/10.1007/978-3-319-97765-2 Library of Congress Control Number: 2018964571 © Springer Nature Switzerland AG 2019 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Preface

This inaugural edition of Endocrine Disorders in Kidney Disease: Diagnosis and Treatment is dedicated to examining the complex interplay between endocrine and kidney disorders and how this interrelationship impacts patients with chronic kidney disease, including those receiving renal replacement therapy in the form of dialysis and kidney transplantation. Indeed, chronic kidney disease patients are a unique population among whom a myriad of hormonal derangements may exist. While there has been growing appreciation of this important link between endocrinology and nephrology, many endocrine disorders may remain latent and under-recognized among kidney disease patients. Hence, this scholarly work is the product of a collaborative effort among experts in areas of endocrinology and nephrology in order to provide a comprehensive overview of the most relevant endocrine disorders observed in the chronic kidney disease population. Part 1 entitled Diabetes, Insulin, Resistance, and the Metabolic Syndrome presents a practical overview of areas commonly encountered in the clinical management of diabetic kidney disease patients, as well as kidney transplant recipients who develop new onset diabetes. Part 2 entitled Thyroid Dysfunction presents innovative themes pertaining to the high prevalence of thyroid dysfunction in kidney disease, including real-world interpretation of thyroid functional derangements and emerging data on thyroid dysfunction and outcomes in the chronic kidney disease population. Part 3 presents highly pertinent information on Gonadal Disorders, which include testosterone deficiency and other testicular conditions, as well as amenorrhea and estrogen disorders in the chronic kidney disease population. Also included in this section is a chapter on pregnancy in kidney disease describing maternal, fetal, and obstetric outcomes, as well as general principles of management. Part 4 entitled Dyslipidemia provides valuable insights into the vast spectrum of lipid disorders associated with chronic kidney disease and nephrotic syndrome, as well as a rigorous summary of existing evidence and clinical practice guidelines addressing the management of dyslipidemia in kidney disease. Part 5 provides an extensive overview of the full-spectrum of Mineral Bone Disorders encountered in kidney disease, including calcium, phosphate, fibroblast growth factor 23, vitamin D, and parathyroid hormone alterations; osteoporosis and osteomalacia; and mineral bone derangements observed in kidney transplantation. Emerging data on Obesity and Adipokines in kidney disease are presented in Part 6. Then in Part 7 entitled Other Pituitary Disorders, experts in the field describe v

Preface

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pituitary disorders in kidney disease including growth hormone ­disorders and abnormal stature, as well as prolactin, glucocorticoid, and arginine vasopressin derangements. Finally, Part 8 synthesizes many of the aforementioned themes by describing the Multi-System Implications of Endocrine Derangements in Kidney Disease, including endocrine derangements in acute kidney injury, as well as the interaction between nutrition and endocrine disorders in kidney disease. We hope that the insights provided by this scholarly endeavor will engender greater understanding of the magnitude of impact that endocrine disorders have upon the kidney disease population, as well as identification of persistent gaps in knowledge that point toward future areas of investigation, with the overarching goal of improving the health and survival of chronic kidney disease patients. We thank all of our authors for their extraordinary expertise and valuable contributions, as well as the Springer editorial team for their tremendous support, which made the development of this unique textbook and resource possible. Orange, CA, USA  Orange, CA, USA  Los Angeles, CA, USA 

Connie M. Rhee Kamyar Kalantar-Zadeh Gregory A. Brent

Contents

Part I Diabetes, Insulin Resistance, and the Metabolic Syndrome 1 Insulin Resistance and the Metabolic Syndrome in Kidney Disease (e.g., the Cardiorenal Metabolic Syndrome). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Vikram Patney, Sivakumar Ardhanari, and Adam Whaley-Connell 2 Diabetic Kidney Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Robert C. Stanton 3 Glucose Homeostasis and the Burnt-Out Diabetes Phenomenon in Patients with Kidney Disease. . . . . . . . . . . . . 27 Masanori Abe, Csaba P. Kovesdy, and Kamyar Kalantar-Zadeh 4 Glycemic Metrics and Targets in Kidney Disease . . . . . . . . . . 39 Joshua J. Neumiller and Irl B. Hirsch 5 Diabetic Pharmacotherapies in Kidney Disease. . . . . . . . . . . . 49 Deborah A. Chon, Rachael T. Oxman, Rashmi S. Mullur, and Jane Eileen Weinreb 6 Diabetes Mellitus and Renal Transplantation . . . . . . . . . . . . . 75 Curtiss B. Cook and Harini Chakkera Part II Thyroid Dysfunction 7 Evaluating Thyroid Function Tests in Patients with Kidney Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 Stephanie Smooke Praw, Jennifer Sue An Way, and Rebecca Weiss 8 Thyroid Status and Outcomes in Kidney Disease . . . . . . . . . . 97 Connie M. Rhee, Gregory A. Brent, and Kamyar Kalantar-Zadeh

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Part III Gonadal Disorders 9 Testosterone Deficiency and Other Testicular Disorders in Kidney Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 Anna L. Goldman and Shalender Bhasin 10 Amenorrhea and Estrogen Disorders in Women with Kidney Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127 Kavitha Vellanki and Holly Kramer 11 Pregnancy in Kidney Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . 139 Madeleine V. Pahl Part IV Dyslipidemia 12 Lipid Disorders Associated with Chronic Kidney Disease and Nephrotic Syndrome . . . . . . . . . . . . . . . . 153 Hamid Moradi and Nosratola D. Vaziri 13 Drugs for Treatment of Dyslipidemia Available in the USA. . . . 171 Elani Streja and Dan A. Streja Part V Mineral Bone Disorders 14 Calcium Homeostasis in Kidney Disease . . . . . . . . . . . . . . . . . 199 Michel Chonchol and Jessica Kendrick 15 Phosphorus Retention and Elevated FGF-23 in Chronic Kidney Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207 Yoshitsugu Obi and Connie M. Rhee 16 Vitamin D and Parathyroid Hormone in Kidney Disease. . . . 223 Sagar U. Nigwekar 17 Management of Bone Disorders in Kidney Disease. . . . . . . . . 231 Stuart M. Sprague 18 Mineral and Bone Disorders Following Renal Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 Hatem Amer and Rajiv Kumar Part VI Obesity and Adipokines 19 Obesity in Kidney Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265 Peter Stenvinkel 20 Adiponectin and Leptin in Kidney Disease Patients. . . . . . . . 277 Jerry Zhong Yu, Kamyar Kalantar-Zadeh, and Connie M. Rhee

Contents

Contents

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Part VII Other Pituitary Disorders 21 Growth Hormone Disorders and Abnormal Stature in Kidney Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293 Amira Al-Uzri, Annabelle N. Chua, and Bradley A. Warady 22 Other Pituitary Disorders and Kidney Disease. . . . . . . . . . . . 309 Wenyu Huang and Mark E. Molitch 23 Endocrine System in Acute Kidney Injury. . . . . . . . . . . . . . . . 321 Alice Sabatino, Graziano Ceresini, Michela Marina, and Enrico Fiaccadori 24 Nutrition and Endocrine Disorders in Kidney Disease. . . . . . 333 Anuja Shah and Joel Kopple Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347

Contributors

Masanori Abe  Division of Nephrology, Hypertension, and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan Amira  Al-Uzri Division of Pediatric Kidney Services and Hypertension, Department of Pediatrics, Oregon Health and Science University, Portland, OR, USA Hatem  Amer Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA Sivakumar  Ardhanari Divisions of Nephrology and Cardiovascular Medicine, Department of Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO, USA Shalender  Bhasin Research Program in Men’s Health: Aging and Metabolism, Brigham and Women’s Hospital/Harvard Medical School, Boston, MA, USA Gregory A. Brent  Division of Endocrinology, Diabetes, and Hypertension, Departments of Medicine and Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Graziano  Ceresini Endocrinology of the Development and Aging Unit, Parma University Medical School, Parma, PR, Italy Harini  Chakkera Division of Nephrology, Mayo Clinic, Scottsdale, AZ, USA Michel Chonchol  Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Hospital, Aurora, CO, USA Deborah  A.  Chon  Division of Diabetes, Endocrinology, and Metabolism, David Geffen School of Medicine at UCLA, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA Annabelle N. Chua  Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA Curtiss  B.  Cook Division of Endocrinology, Mayo Clinic College of Medicine, Scottsdale, AZ, USA

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Enrico  Fiaccadori  Renal Failure Unit, Parma University Medical School, Parma, PR, Italy Anna  L.  Goldman Research Program in Men’s Health: Aging and Metabolism, Brigham and Women’s Hospital/Harvard Medical School, Boston, MA, USA Irl  B.  Hirsch Division of Metabolism, Endocrinology, and Nutrition, University of Washington School of Medicine, Seattle, WA, USA Wenyu  Huang Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Kamyar  Kalantar-Zadeh Division of Nephrology and Hypertension, Departments of Medicine, Pediatrics, Public Health, and Nursing Sciences, University of California Irvine School of Medicine, Orange, CA, USA Jessica Kendrick  Division of Renal Diseases and Hypertension, Department of Medicine, Denver Health Medical Center and University of Colorado, Denver, CO, USA Joel  Kopple Division of Nephrology, Department of Medicine, HarborUCLA Medical Center, Torrance, CA, USA Csaba  P.  Kovesdy Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA Holly  Kramer Departments of Public Health Sciences and Medicine, Loyola University Medical Center, Maywood, IL, USA Rajiv  Kumar  Division of Nephrology and Hypertension, Departments of Internal Medicine, Biochemistry, and Molecular Biology, Mayo Clinic, Rochester, MN, USA Michela Marina  Endocrinology of the Development and Aging Unit, Parma University Medical School, Parma, PR, Italy Mark  E.  Molitch  Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Hamid  Moradi Division of Nephrology and Hypertension, University of California Irvine School of Medicine, Orange, CA, USA Tibor Rubin Veterans Affairs Medical Center, Long Beach, CA, USA Rashmi S. Mullur  Division of Diabetes, Endocrinology, and Metabolism, David Geffen School of Medicine at UCLA, VA Greater Los Angeles Health System, Los Angeles, CA, USA Joshua  J.  Neumiller Department of Pharmacotherapy, Washington State University, Spokane, WA, USA Sagar  U.  Nigwekar Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

Contributors

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Yoshitsugu  Obi  Division of Nephrology and Hypertension, University of California Irvine School of Medicine, Orange, CA, USA Rachael T. Oxman  Division of Diabetes, Endocrinology, and Metabolism, David Geffen School of Medicine at UCLA, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA Madeleine V. Pahl  Division of Nephrology and Hypertension, University of California Irvine School of Medicine, Orange, CA, USA Vikram  Patney Division of Nephrology, Department of Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO, USA Stephanie  Smooke  Praw Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Connie M. Rhee  Division of Nephrology and Hypertension, Departments of Medicine and Public Health, University of California Irvine School of Medicine, Orange, CA, USA Alice  Sabatino Renal Failure Unit, Parma University Medical School, Parma, PR, Italy Anuja  Shah Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, Torrance, CA, USA Stuart M. Sprague  Division of Nephrology and Hypertension, NorthShore University HealthSystem, Evanston, IL, USA University of Chicago Pritzker School of Medicine, Chicago, IL, USA Robert  C.  Stanton Kidney and Hypertension Section, Department of Medicine, Joslin Diabetes Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Peter  Stenvinkel Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden Karolinska University Hospital, Stockholm, Sweden Dan A. Streja  Department of Medicine, David Geffen School of Medicine at UCLA, VA Greater Los Angeles Health Care System, Los Angeles, CA, USA Elani  Streja Division of Nephrology and Hypertension, University of California Irvine School of Medicine, Orange, CA, USA Tibor Rubin Veterans Affairs Medical Center, Long Beach, CA, USA Nosratola D. Vaziri  Division of Nephrology and Hypertension, University of California Irvine School of Medicine, Orange, CA, USA Kavitha  Vellanki Department of Medicine, Loyola University Medical Center, Maywood, IL, USA

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Bradley  A.  Warady University of Missouri—Kansas City School of Medicine, Kansas City, MO, USA Division of Pediatric Nephrology, Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO, USA Jennifer  Sue  An  Way Division of Endocrinology, Metabolism, and Hypertension, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Jane Eileen Weinreb  Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA Rebecca  Weiss Department of Endocrinology, Kaiser Permanente— Woodland Hills, Woodland Hills, CA, USA Adam Whaley-Connell  Division of Nephrology, Department of Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO, USA Research Service, University of Missouri School of Medicine, Harry S. Truman VA Medical Center, Columbia, MO, USA Jerry  Zhong  Yu Nephrology Associates Medical Group, Riverside, CA, USA

Contributors

Part I Diabetes, Insulin Resistance, and the Metabolic Syndrome

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Insulin Resistance and the Metabolic Syndrome in Kidney Disease (e.g., the Cardiorenal Metabolic Syndrome) Vikram Patney, Sivakumar Ardhanari, and Adam Whaley-Connell

Introduction The metabolic syndrome is a collection of abnormalities that are risk factors for the development of cardiovascular and chronic kidney disease (CKD). While current dogma suggest that obesity is at the core of this constellation of risk factors, the association between blood pressure and diabetes was described as early as 1921 [1–4]. Then during the 1988 Banting V. Patney (*) Division of Nephrology and Hypertension, Department of Medicine, University of MissouriColumbia School of Medicine, Columbia, MO, USA e-mail: [email protected] S. Ardhanari Division of Nephrology and Hypertension, Department of Medicine, University of MissouriColumbia School of Medicine, Columbia, MO, USA Division of Cardiovascular Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO, USA A. Whaley-Connell Division of Nephrology and Hypertension, Department of Medicine, University of MissouriColumbia School of Medicine, Columbia, MO, USA Division of Cardiovascular Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO, USA Research Service, University of Missouri School of Medicine, Harry S. Truman VA Medical Center, Columbia, MO, USA

lecture, G.M. Reaven suggested that the clustering of risk factors in an individual including high blood pressure, impaired glucose tolerance, and dyslipidemia was associated with coronary artery disease. At that time he grouped these metabolic disorders and referred to them as “syndrome X.” He proposed that resistance to insulin-stimulated glucose uptake and compensatory hyperinsulinemia contributed to the development of non-­ insulin-­ dependent diabetes mellitus, hypertension, and coronary artery disease [5]. This interest in “syndrome X” became an area of investigative interest for many in the 1990s and early 2000s that ultimately led to a better understanding of the relationship between obesity, insulin resistance, and cardiovascular and kidney disease. In modern terms, the “metabolic syndrome” refers to a set of physical and laboratory parameters whose co-occurrence in an individual may help clinicians identify the presence of insulin resistance as a chance to intervene early in the course of cardiovascular disease [6, 7]. In addition to syndrome X, other terms that have been used to describe a similar group of risk factors are “insulin resistance syndrome,” “dysmetabolic syndrome X,” and also “Reaven’s syndrome.” Since then, a number of organizations have sought to name and define this syndrome including the National Cholesterol Education Program Adult Treatment Panel III (ATP III), World

© Springer Nature Switzerland AG 2019 C. M. Rhee et al. (eds.), Endocrine Disorders in Kidney Disease, https://doi.org/10.1007/978-3-319-97765-2_1

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Health Organization, American Association of Clinical Endocrinologists, European Group for the Study of Insulin Resistance, and International Diabetes Federation among others. The common criteria for this syndrome consistently rely on the presence of obesity and insulin resistance. It should be noted the central difference between the various organizations in describing the syndrome is in measurement thresholds of insulin resistance, blood pressure, obesity, and/or the presence of microalbuminuria. There is a well-described relationship between diabetes and CKD; however, over the past decade, there has been considerable interest in the effects of insulin resistance, distinct from that of diabetes, on CKD. Obesity and the presence of the compensatory hyperinsulinemia from insulin resistance have emerged as important contributors to the development of CKD. Thereby in this chapter, we will focus on the importance of the metabolic syndrome and insulin resistance in kidney disease and then review some of the important mechanisms that underlie this relationship [8–12].

Definition(s) of the Cardiorenal Metabolic Syndrome Over the years, the diagnostic criteria for the identification of the metabolic syndrome have evolved. There have been a number of diagnostic criteria used in the cardiorenal metabolic syndrome to help identify the heightened risk for diabetes, cardiovascular, and, for our discussion, kidney disease. As per Reaven’s original description, syndrome X referred to the following risk factors: glucose intolerance, dyslipidemia, and hypertension [5]. Reaven proposed a causative role for insulin resistance. However, his description did not mention central obesity, which is now viewed by most as the unifying feature of the syndrome. In 1999, a World Health Organization (WHO) diabetes group proposed a definition that included impaired glucose tolerance or diabetes mellitus and/or insulin resistance together with two or more of the following: raised arterial pressure

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≥160/90  mmHg, plasma triglycerides >150  mg/ dl, HDL 0.85  in women and/or BMI >30 kg/m2, and/or microalbuminuria ≥20 μg/min or albumin/creatinine ratio ≥20  mg/gm [13]. Subsequently, the European Group for the Study of Insulin Resistance suggested some modifications to the WHO definition of metabolic syndrome. They excluded diabetic individuals as the current thought at that time was that there was no simple way to measure insulin resistance and suggested different cutoffs for other criteria [14]. The NCEP:ATP III proposed a definition that focused on facilitating diagnosis and risk reduction for individuals at high risk for cardiovascular disease [15]. The ATP III suggested the diagnosis of metabolic syndrome with the presence of three or more from the following criteria: waist circumference >40 inches in men or >35 inches in women, triglycerides ≥150  mg/dl, high-density lipoprotein cholesterol