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Tenth Edition BRENNER & RECTOR’S THE KIDNEY VOLUME 1 Karl Skorecki, MD, Maarten W. Taal, FRCP(C), FASN MBChB, MMed, MD, Annie Chutick Professor and Chair in FCP(SA), FRCP Medicine (Nephrology) Professor of Medicine Technion—Israel Institute of Technology Division of Medical Sciences and Director of Medical and Research Graduate Entry Medicine Development University of Nottingham Rambam Health Care Campus Honorary Consultant Nephrologist Haifa, Israel Department of Renal Medicine Royal Derby Hospital Glenn M. Chertow, MD Derby, United Kingdom Norman S. Coplon/Satellite Healthcare Professor of Medicine Alan S.L. Yu, MD Chief, Division of Nephrology Harry Statland and Solon Summerfield Stanford University School of Medicine Professor of Medicine Palo Alto, California Director, Division of Nephrology and Hypertension and The Kidney Institute Philip A. Marsden, MD University of Kansas Medical Center Kansas City, Kansas Professor of Medicine Elisabeth Hofmann Chair in Translational Research SPECIAL ASSISTANT TO THE EDITORS Oreopoulos-Baxter Division Director of Walter G. Wasser, MD Nephrology Vice Chair Research, Department of Attending Physician, Division of Medicine Nephrology University of Toronto Mayanei HaYeshua Medical Center Toronto, Ontario, Canada Bnei Brak, Israel; Rambam Health Care Campus Haifa, Israel i 1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899 BRENNER AND RECTOR’S THE KIDNEY, TENTH EDITION ISBN: 978-1-4557-4836-5 Copyright © 2016 by Elsevier, Inc. All rights reserved. Volume 1 part number 9996096807 Volume 2 part number 9996096866 No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Previous editions copyrighted 2012, 2008, 2004, 2000, 1996, 1991, 1986, 1981, 1976. Library of Congress Cataloging-in-Publication Data Brenner & Rector’s the kidney / [edited by] Karl Skorecki, Glenn M. Chertow, Philip A. Marsden, Maarten W. Taal, Alan S.L. Yu ; special assistant to the editors, Walter G. Wasser.—10th edition. p. ; cm. Brenner and Rector’s the kidney Kidney Includes bibliographical references and index. ISBN 978-1-4557-4836-5 (hardcover : alk. paper) I. Skorecki, Karl, editor. II. Chertow, Glenn M., editor. III. Marsden, Philip A., editor. IV. Taal, Maarten W., editor. V. Yu, Alan S. L., editor. VI. Title: Brenner and Rector’s the kidney. VII. Title: Kidney. [DNLM: 1. Kidney Diseases. 2. Kidney—physiology. 3. Kidney—physiopathology. WJ 300] RC902 616.6′1—dc23 2015033607 Content Strategist: Kellie Heap Senior Content Development Specialist: Joan Ryan Publishing Services Manager: Jeffrey Patterson Senior Project Manager: Mary Pohlman Senior Book Designer: Margaret Reid Printed in United States of America. Last digit is the print number: 9 8 7 6 5 4 3 2 1 Dedicated to our patients and to our students —who provide us with the inspiration to learn, teach, and discover. Contributors Andrew Advani, BSc, MBChB(Hons), PhD, FRCP(UK) Kara N. Babaian, MD Assistant Professor of Medicine Assistant Professor of Clinical Urology University of Toronto Department of Urology St. Michael’s Hospital University of California, Irvine Toronto, Ontario, Canada Orange, California Chapter 13, Vasoactive Molecules and the Kidney Chapter 41, Kidney Cancer Michael Allon, MD Colin Baigent, FFPH, FRCP Professor of Medicine Professor of Epidemiology Division of Nephrology Clinical Trial Service Unit University of Alabama at Birmingham Nuffield Department of Population Health Birmingham, Alabama Oxford, United Kingdom Chapter 70, Interventional Nephrology Chapter 56, Cardiovascular Aspects of Kidney Disease Amanda Hyre Anderson, PhD, MPH Sevcan A. Bakkaloglu, MD Assistant Professor of Epidemiology Professor of Pediatrics Center for Clinical Epidemiology and Biostatistics Head, Division of Pediatric Nephrology and Perelman School of Medicine Rheumatology University of Pennsylvania Gazi University School of Medicine Philadelphia, Pennsylvania Ankara, Turkey Chapter 21, Demographics of Kidney Disease Chapter 74, Diseases of the Kidney and Urinary Tract in Children Gerald B. Appel, MD Professor of Medicine George L. Bakris, MD Director of Clinical Nephrology Professor of Medicine Division of Nephrology Department of Medicine Columbia University Medical Center University of Chicago Medicine New York, New York ASH Comprehensive Hypertension Center Chapter 33, Secondary Glomerular Disease Chicago, Illinois Chapter 47, Primary and Secondary Hypertension Suheir Assady, MD, PhD Director, Department of Nephrology and Hypertension Gavin J. Becker, MD, FRACP Rambam Health Care Campus Professor Haifa, Israel Department of Nephrology Chapter 79, Near and Middle East Royal Melbourne Hospital and University of Melbourne Melbourne, Victoria, Australia Anthony Atala, MD Chapter 82, Oceania Region Director, Wake Forest Institute for Regenerative Medicine Rachel Becker-Cohen, MD William H. Boyce Professor and Chair Pediatric Nephrology Department of Urology Shaare Zedek Medical Center Wake Forest School of Medicine The Hebrew University School of Medicine Winston-Salem, North Carolina Jerusalem, Israel Chapter 86, Tissue Engineering, Stem Cells, and Cell Therapy Chapter 76, Renal Replacement Therapy (Dialysis and in Nephrology Transplantation) in Pediatric End-Stage Kidney Disease Paul Ayoub, MD Theresa J. Berndt Specialized Medicine Department of Medicine University of Montréal Division of Nephrology and Hypertension Montréal, Quebec, Canada Mayo Clinic College of Medicine Chapter 69, Elimination Enhancement of Poisons Mayo Clinic Rochester, Minnesota Chapter 7, The Regulation of Calcium, Magnesium, and Phosphate Excretion by the Kidney iv CONTRIBUTORS v Jeffrey S. Berns, MD Richard M. Breyer, PhD Professor of Medicine Professor of Medicine Perelman School of Medicine Professor of Biochemistry University of Pennsylvania Ruth King Scoville Chair in Medicine Philadelphia, Pennyslvania Professor of Pharmacology Chapter 21, Demographics of Kidney Disease Vanderbilt University Nashville, Tennessee Prof John F. Bertram, BSc(Hons), PhD, FASN, DSc Chapter 14, Arachidonic Acid Metabolites and the Kidney Professor of Anatomy and Developmental Biology Monash University Dennis Brown, PhD Clayton, Victoria, Australia Department of Medicine Chapter 23, Nephron Endowment and Developmental Harvard Medical School Programming of Blood Pressure and Renal Function Center for Systems Biology Program in Membrane Biology and Division of Vivek Bhalla, MD Nephrology Assistant Professor of Medicine/Nephrology Massachusetts General Hospital Stanford University School of Medicine Boston, Massachussets Stanford, California Chapter 11, The Cell Biology of Vasopressin Action Chapter 12, Aldosterone and Mineralocorticoid Receptors: Renal and Extrarenal Roles Carlo Brugnara, MD Professor of Pathology Daniel G. Bichet, MD Harvard Medical School Professor of Medicine and Physiology Director, Hematology Laboratory University of Montréal Boston Children’s Hospital Nephrologist Boston, Massachusetts Department of Medicine Chapter 57, Hematologic Aspects of Kidney Disease Hôpital du Sacré-Coeur de Montréal Montréal, Quebec, Canada Stéphan Busque, MD Chapter 45, Inherited Disorders of the Renal Tubule Professor of Surgery (Abdominal Transplantation) Director, Adult Kidney and Pancreas Transplant Program Alain Bonnardeaux, MD, PhD Stanford University Full Professor of Medicine Stanford, California University of Montréal Chapter 72, Clinical Management of the Adult Kidney Nephrologist Transplant Recipient Hôpital Maisonneuve-Rosemont Montréal, Quebec, Canada Juan Jesús Carrero, Pharm, PhD, MBA Chapter 45, Inherited Disorders of the Renal Tubule Associate Professor Karolinska Institutet William D. Boswell, Jr., MD, FACR Stockholm, Sweden Professor and Chairman Chapter 58, Endocrine Aspects of Chronic Kidney Disease Department of Radiology City of Hope National Medical Center Daniel Cattran, MD, FRCP(C), FACP Duarte, California Professor of Medicine Chapter 28, Diagnostic Kidney Imaging University of Toronto Senior Scientist Barry M. Brenner, MD, AM(Hon), DSc(Hon), Toronto General Research Institute DMSc(Hon), MD(Hon), Dipl(Hon), FRCP(London, Toronto General Hospital Hon) Toronto, Ontario, Canada Samuel A. Levine Distinguished Professor of Medicine Chapter 34, Overview of Therapy for Glomerular Disease Harvard Medical School Director Emeritus, Renal Division, and Senior Physician James C. M. Chan, MD Department of Medicine Professor of Pediatrics Brigham and Women’s Hospital Tufts University School of Medicine Boston, Massachusetts Director of Research Chapter 3, The Renal Circulations and Glomerular The Barbara Bush Children’s Hospital Ultrafiltration Maine Medical Center Portland, Maine Chapter 75, Fluid, Electrolyte, and Acid-Base Disorders in Children vi CONTRIBUTORS Anil Chandraker, MD Shawn E. Cowper, MD Associate Professor of Medicine Associate Professor of Dermatology and Pathology Harvard Medical School Yale University Brigham and Women’s Hospital New Haven, Connecticut Schuster Family Transplantation Research Center Chapter 60, Dermatologic Conditions in Kidney Disease Boston, Massachusetts Chapter 71, Transplantation Immunobiology Paolo Cravedi, MD, PhD IRCCS-Istituto di Ricerche Farmacologiche Mario Negri Katrina Chau, MBBS, FRACP Centro Anna Maria Astori, Science and Technology Park Department of Nephrology Kilometro Rosso University of British Columbia Bergamo, Italy Vancouver, British Columbia, Canada; Chapter 35, Microvascular and Macrovascular Diseases Department of Nephrology of the Kidney Liverpool Hospital Sydney, Australia Vivette D’Agati, MD Chapter 26, Laboratory Assessment of Kidney Disease: Professor of Pathology Glomerular Filtration Rate, Urinalysis, and Proteinuria Columbia University College of Physicians and Surgeons Director, Renal Pathology Laboratory Glenn M. Chertow, MD, MPH Columbia University Medical Center Norman S. Coplon/Satellite Healthcare New York, New York Professor of Medicine Chapter 33, Secondary Glomerular Disease Department of Medicine, Division of Nephrology Stanford University School of Medicine Mogamat Razeen Davids, MD Palo Alto, California Division of Nephrology Chapter 84, Health Disparities in Nephrology Stellenbosch University and Tygerberg Hospital Cape Town, South Africa Devasmita Choudhury, MD Chapter 27, Interpretation of Electrolyte and Acid-Base Associate Professor of Medicine Parameters in Blood and Urine University of Virginia School of Medicine Virginia Tech-Carilion School of Medicine Scott E. Delacroix, Jr., MD Chief of Nephrology Assistant Professor of Urology Director of Dialysis and Interventional Nephrology Director of Urologic Oncology Salem Veterans Affairs Medical Center Department of Oncology Salem, Virginia Louisiana State University School of Medicine Chapter 24, Aging and Kidney Disease New Orleans, Louisiana Chapter 41, Kidney Cancer John F. Collins, MBChB, FRACP Clinical Associate Professor of Renal Medicine Bradley M. Denker, MD Auckland City Hospital Associate Professor of Medicine Auckland, New Zealand Harvard Medical School Chapter 82, Oceania Region Clinical Chief, Renal Division Beth Israel Deaconess Medical Center H. Terence Cook, MB, BS, FRCPath Boston, Massachusetts Professor, Department of Medicine Chapter 68, Plasmapheresis Centre for Complement and Inflammation Research Imperial College London Thomas A. Depner, MD Hammersmith Hospital Professor of Medicine London, United Kingdom Department of Internal Medicine/Nephrology Chapter 29, The Kidney Biopsy University of California Davis Health System Sacramento, California Ricardo Correa-Rotter, MD Chapter 65, Hemodialysis Head, Department of Nephrology and Mineral Metabolism Thomas D. DuBose, Jr., MD Instituto Nacional de Ciencias Médicas y Nutrición Professor Emeritus of Medicine Salvador Zubirán Department of Internal Medicine Mexico City, Mexico Wake Forest School of Medicine Chapter 66, Peritoneal Dialysis Winston-Salem, North Carolina Chapter 17, Disorders of Acid-Base Balance CONTRIBUTORS vii Vinay A. Duddalwar, MD, FRCR Harold I. Feldman, MD, MSCE Associate Professor of Clinical Radiology and Urology Professor of Epidemiology and Medicine Section Chief, Abdominal Imaging Perelman School of Medicine Medical Director, Imaging University of Pennsylvania USC Norris Comprehensive Cancer Center and Hospital Philadelphia, Pennyslvania University of Southern California Chapter 21, Demographics of Kidney Disease Keck School of Medicine Los Angeles, California Bo Feldt-Rasmussen, MD, DMSc Chapter 28, Diagnostic Kidney Imaging Professor and Head of Clinic Department of Nephrology Kai-Uwe Eckardt, MD Rigshospitalet University of Copenhagen Professor of Medicine Copenhagen, Denmark Chair of Nephrology and Hypertension Chapter 39, Diabetic Nephropathy Friedrich-Alexander University Erlangen-Nürnberg Erlangen, Germany Robert A. Fenton, PhD Chapter 57, Hematologic Aspects of Kidney Disease Professor of Molecular Cell Biology Department of Biomedicine Meghan J. Elliott, MD Aarhus University Nephrology Resident Aarhus, Denmark Department of Medicine Chapter 2, Anatomy of the Kidney University of Calgary Chapter 10, Urine Concentration and Dilution Calgary, Alberta, Canada Chapter 11, The Cell Biology of Vasopressin Action Chapter 85, Care of the Older Adult with Chronic Kidney Disease Andrew Z. Fenves, MD, FACP, FASN Inpatient Clinical Educator William J. Elliott, MD, PhD Massachusetts General Hospital Professor of Preventive Medicine Associate Professor of Medicine Internal Medicine and Pharmacology Harvard Medical School Pacific Northwest University of Health Sciences Boston, Massachusetts Yakima, Washington Chapter 25, Approach to the Patient with Kidney Disease Chapter 47, Primary and Secondary Hypertension Kevin W. Finkel, MD, FACP, FASN, FCCM David H. Ellison, MD Department of Internal Medicine Professor of Internal Medicine Director, Division of Renal Diseases and Hypertension Oregon Health & Science University University of Texas Health Science Center at Houston Portland, Oregon Department of Internal Medicine Chapter 51, Diuretics Section of Nephrology The University of Texas MD Anderson Cancer Center Michael Emmett, MD Houston, Texas Chief of Internal Medicine Chapter 42, Onco-Nephrology: Kidney Disease in Patients Department of Internal Medicine with Cancer Baylor University Medical Center Dallas, Texas; Paola Fioretto, MD Professor of Medicine Associate Professor Internal Medicine Department of Medical and Surgical Sciences Texas A&M College of Medicine University of Padova Medical School Baylor University Medical Center Padova, Italy Denton, Texas; Chapter 39, Diabetic Nephropathy Clinical Professor of Medicine University of Texas Southwestern Medical School Damian G. Fogarty, BSc, MD, FRCP Dallas, Texas Consultant Nephrologist Chapter 25, Approach to the Patient with Kidney Disease Regional Nephrology and Transplant Unit Belfast City Hospital at the Belfast Health and Ronald J. Falk, MD Social Care Trust Chair, Department of Medicine Belfast, Northern Ireland Director, UNC Kidney Center Chapter 62, A Stepped Care Approach to the Management of The University of North Carolina Chronic Kidney Disease Chapel Hill, North Carolina Chapter 32, Primary Glomerular Disease viii CONTRIBUTORS Denis Fouque, MD, PhD Mitchell L. Halperin, MD Professor of Nephrology Division of Nephrology Chief, Division of Nephrology St. Michael’s Hospital Université Claude Bernard and Centre Hospitalier Lyon University of Toronto Sud Toronto, Canada Lyon, France Chapter 27, Interpretation of Electrolyte and Acid-Base Chapter 61, Dietary Approaches to Kidney Diseases Parameters in Blood and Urine Yaacov Frishberg, MD Donna S. Hanes, MD, FACP Director, Pediatric Nephrology Clinical Associate Professor of Medicine Shaare Zedek Medical Center Clerkship Director, Internal Medicine The Hebrew University School of Medicine University of Maryland Medical Systems Jerusalem, Israel Baltimore, Maryland Chapter 76, Renal Replacement Therapy (Dialysis and Chapter 50, Antihypertensive Therapy Transplantation) in Pediatric End-Stage Kidney Disease Chuan-Ming Hao, MD Jørgen Frøkiaer, MD, DMSci Professor Head of Department of Nuclear Medicine and Medicine/Nephrology Molecular Imaging Huashan Hospital Fudan University Department of Clinical Medicine Shanghai, China Aarhus University and Aarhus University Hospital Chapter 81, The Far East Aarhus, Denmark Chapter 38, Urinary Tract Obstruction David C. H. Harris, MD, BS, FRACP Associate Dean and Head of School John W. Funder, MD, PhD, FRCP, FRACP Sydney Medical School—Westmead Distinguished Scholar The University of Sydney Steroid Biology Sydney, New South Wales, Australia Hudson Institute of Medical Research Chapter 82, Oceania Region Clayton, Victoria, Australia Chapter 12, Aldosterone and Mineralocorticoid Receptors: Peter C. Harris, PhD Renal and Extrarenal Roles Professor of Biochemistry/Molecular Biology Professor of Medicine Marc Ghannoum, MD Nephrology and Hypertension Associate Professor Mayo Clinic Specialized Medicine Rochester, Minnesota University of Montréal Chapter 46, Cystic Diseases of the Kidney Verdun Hospital Montréal, Quebec, Canada Raymond C. Harris, MD Chapter 69, Elimination Enhancement of Poisons Ann and Roscoe Robinson Professor of Medicine Chief, Division of Nephrology and Hypertension Richard E. Gilbert, MBBS, PhD, FRACP, FRCPC, Vanderbilt University School of Medicine FACP, FASN Nashville, Tennessee Professor of Medicine Chapter 14, Arachidonic Acid Metabolites and the Kidney University of Toronto St. Michael’s Hospital Richard Haynes, DM, FRCP Toronto, Ontario, Canada Associate Professor Chapter 13, Vasoactive Molecules and the Kidney Clinical Trial Service Unit and Epidemiological Studies Unit Paul Goodyer, MD Nuffield Department of Population Health Professor of Pediatrics Honorary Consultant in Nephrology McGill University Oxford Kidney Unit Montréal, Quebec, Canada Churchill Hospital Chapter 23, Nephron Endowment and Developmental Oxford, United Kingdom Programming of Blood Pressure and Renal Function Chapter 56, Cardiovascular Aspects of Kidney Disease Yoshio N. Hall, MD, MS Brenda R. Hemmelgarn, MD, PhD Associate Professor of Medicine Professor of Medicine Department of Medicine, Division of Nephrology University of Calgary University of Washington Calgary, Alberta, Canada Seattle, Washington Chapter 85, Care of the Older Adult with Chronic Chapter 84, Health Disparities in Nephrology Kidney Disease CONTRIBUTORS ix Friedhelm Hildebrandt, MD Holly Hutton, MBBS, FRACP Warren E. Grupe Professor of Pediatrics Department of Nephrology Harvard Medical School University of British Columbia Investigator, Howard Hughes Medical Institute Vancouver, British Columbia, Canada; Chief, Division of Nephrology Department of Nephrology Boston Children’s Hospital Monash Health Boston, Massachusetts Clayton, Victoria, Australia Chapter 43, Genetic Basis of Kidney Disease Chapter 26, Laboratory Assessment of Kidney Disease: Glomerular Filtration Rate, Urinalysis, and Proteinuria Michelle A. Hladunewich, MD, MSc Associate Professor of Medicine Hossein Jadvar, MD, PhD, MPH, MBA, FACNM University of Toronto Associate Professor of Radiology Scientist, Sunnybrook Research Institute Associate Professor of Biomedical Engineering Sunnybrook Health Sciences Centre University of Southern California Toronto, Ontario, Canada Keck School of Medicine Chapter 34, Overview of Therapy for Glomerular Disease Los Angeles, California Chapter 28, Diagnostic Kidney Imaging Kevin Ho, MD Associate Professor of Medicine & Clinical and J. Charles Jennette, MD Translational Science Kenneth M. Brinkhous Distinguished Professor and Chair Renal-Electrolyte Division Department of Pathology and Laboratory Medicine University of Pittsburgh The University of North Carolina Pittsburgh, Pennsylvania Chapel Hill, North Carolina Chapter 87, Quality Improvement Initiatives in Kidney Disease Chapter 32, Primary Glomerular Disease Ewout J. Hoorn, MD, PhD Eric Jonasch, MD Associate Professor Associate Professor Department of Internal Medicine, Division of Nephrology Department of Genitourinary Medical Oncology and Transplantation Division of Cancer Medicine Erasmus Medical Center The University of Texas MD Anderson Cancer Center Rotterdam, The Netherlands Houston, Texas Chapter 51, Diuretics Chapter 41, Kidney Cancer Thomas H. Hostetter, MD Kamel S. Kamel, MD Professor of Medicine Division of Nephrology Case Western Reserve University School of Medicine St. Michael’s Hospital Vice Chairman, Research Services University of Toronto University Hospitals Case Medical Center Toronto, Canada Cleveland, Ohio Chapter 27, Interpretation of Electrolyte and Acid-Base Chapter 54, The Pathophysiology of Uremia Parameters in Blood and Urine Fan-Fan Hou, MD S. Ananth Karumanchi, MD Director of Guangdong Provincial Institute of Nephrology Professor Chief and Professor of Division of Nephrology Department of Medicine, Obstetrics, and Gynecology Nanfang Hospital Harvard Medical School Professor of Medicine Howard Hughes Medical Institute and Beth Israel Southern Medical University Deaconess Medical Center Guangzhou, China Boston, Massachusetts Chapter 81, The Far East Chapter 49, Hypertension and Kidney Disease in Pregnancy Chi-yuan Hsu, MD Frieder Keller, MD Professor and Division Chief Professor of Nephrology Division of Nephrology Department of Internal Medicine 1 University of California, San Francisco Ulm University San Francisco, California Ulm, Germany Chapter 20, Epidemiology of Kidney Disease Chapter 64, Drug Dosing Considerations in Patients with Acute Kidney Injury and Chronic Kidney Disease Raymond K. Hsu, MD Assistant Professor of Medicine Division of Nephrology University of California, San Francisco San Francisco, California Chapter 20, Epidemiology of Kidney Disease

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Overcome the toughest clinical challenges in nephrology with Brenner & Rector’s The Kidney -- the most well-known nephrology resource in the world. A diverse team of more than 200 international contributors brings you the latest knowledge and best practices on every front in nephrology worldwide.