Ebook Critical care nephrology (3/E): Part 1

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CRITICAL
CARE
NEPHROLOGY
Third Edition

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Third Edition

CRITICAL
CARE
NEPHROLOGY

Claudio Ronco, MD

John A. Kellum, MD, MCCM

Director, Department of Nephrology, Dialysis
and Transplantation and International
Renal Research Institute (IRRIV)
San Bortolo Hospital
Vicenza, Italy

Director, Center for Critical Care Nephrology
Professor and Vice Chair
Department of Critical Care Medicine
University of Pittsburgh
Pittsburgh, Pennsylvania

Rinaldo Bellomo, MB BS (Hons), MD,
FRACP, FCICM, FAAHMS

Zaccaria Ricci, MD

Department of Intensive Care
Austin Hospital and Royal Melbourne Hospital
Australian and New Zealand Intensive Care
Research Centre
School of Public Health and Preventive
Medicine
Monash University and School of Medicine
The University of Melbourne
Melbourne, Victoria, Australia

Pediatric Cardiac Intensive Care Unit
Department of Pediatric Cardiac Surgery
Bambino Gesù Children’s Hospital, IRCCS
Rome, Italy


1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899

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Critical Care Nephrology, Third Edition

ISBN: 978-0-323-44942-7

Copyright © 2019 by Elsevier, Inc. All rights reserved.
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
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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
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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
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products, instructions, or ideas contained in the material herein.
Previous editions copyrighted 2009 by Saunders, an imprint of Elsevier Inc.; 1998 by Claudio

Ronco, MD, and Rinaldo Bellomo, MD
Library of Congress Cataloging-in-Publication Data
Names: Ronco, C. (Claudio), 1951- editor. | Bellomo, R. (Rinaldo), 1956-editor. | Kellum,
John A., editor. | Ricci, Zaccaria, editor.
Title: Critical care nephrology / editors, Claudio Ronco, Rinaldo Bellomo, John A. Kellum,
Zaccaria Ricci.
Other titles: Critical care nephrology (Ronco)
Description: Third edition. | Philadelphia, PA : Elsevier, Inc., [2018] | Includes bibliographical
references and index.
Identifiers: LCCN 2017004974 | ISBN 9780323449427 (hardcover : alk. paper)
Subjects: | MESH: Kidney Diseases—therapy | Kidney Diseases—complications | Critical Care
Classification: LCC RC903 | NLM WJ 300 | DDC 616.6/1028—dc23 LC record available at
/>Content Strategist: Nancy Anastasi Duffy
Content Development Specialist: Janice Galliard
Publishing Services Manager: Patricia Tannian
Project Manager: Stephanie Turza
Design Direction: Margaret Reid
Printed in the United States of America
Last digit is the print number: 9 8 7 6 5 4 3 2 1


To my wife, Paola, for her love, patience and support.
To Federico, my dear son, now an esteemed colleague.
Claudio Ronco
To my wife, Debbie, for her patience, understanding, and support.
To my daughter, Hilary, may she long continue to pursue excellence
and wisdom. To both for giving my life meaning.
Rinaldo Bellomo
To my parents, John and Barbara, whose support and
encouragement make all things seem possible; to my wonderful

wife, Nita, who keeps my feet on the ground; and to my children,
Brianna and Alston, who have given me the greatest joys
I have ever known.
John A. Kellum
To my mentor, Claudio, the first who showed to me that it is
more important to give than to take, in science and in life. To
my coeditors, because I could collaborate with those who have
previously taught me all of this. To Emanuela, Margherita,
Alessandro e Matteo for the love they brought in my life.
Zaccaria Ricci


Contributors
Robert C. Albright, Jr, MD
Associate Professor of Medicine
Chair and Consultant
Division of Nephrology and
Hypertension
Mayo Clinic
Rochester, Minnesota
Richard Amerling, MD
Associate Professor of Clinical
Medicine
Albert Einstein College of Medicine
of Yeshiva University
Bronx, New York;
Director of Outpatient Dialysis and
Continuous Renal Replacement
Therapy
Beth Israel Medical Center

New York, New York
Paolo Angeli, MD, PhD
Professor of Medicine
Unit of Internal Medicine and
Hepatology
Department of Medicine
University of Padova
Padova, Italy
Maria Lucia Angelotti, MD
Excellence Centre for Research
Transfer and High Education for
the Development of DE NOVO
Therapies (DENOTHE)
Department of Clinical and
Experimental Biomedical
Sciences
University of Florence
Florence, Italy
Massimo Antonelli, MD
Department of Anesthesiology and
Critical Care
Catholic University of the Sacred
Heart
Rome, Italy
Riccardo Antoniotti, MD
Renal Intensive Care Unit
Parma University Hospital
Parma, Italy
Nishkantha Arulkumaran, PhD
Lecturer, Intensive Care Medicine

Bloomsbury Institute of Intensive
Care Medicine
University College London
London, United Kingdom

Pierre Asfar, MD
Département de Réanimation
Médicale et de Médecine
Hyperbare
Centre Hospitalier Universitaire
d’Angers
Laboratoire de Biologie
Neurovasculaire et Mitochondriale
Intégrée
Institut Mitovasc
Université d’Angers
Angers, France
Stephen R. Ash, MD, FACP
Indiana University Health Arnett
HemoCleanse Technologies, LLC
Ash Access Technology
Lafayette, Indiana
Filippo Aucella, MD
Department of Nephrology and
Dialysis
Casa Sollievo della Sofferenza
Research Hospital
San Giovanni Rontondo, Italy
Francesco Aucella, MD
Medical Student

University of Foggia
Foggia, Italy
Samuele Ave, MD
Nuclear Medicine Physician
Department of Nuclear Medicine
San Bortolo Hospital
Vicenza, Italy
Sean M. Bagshaw, MD
Critical Care Medicine
Faculty of Medicine and Dentistry
University of Alberta
Edmonton, Alberta, Canada
Vasanthi Balaraman, MD
Division of Nephrology
Columbia University Medical Center
New York, New York
Ian Baldwin, RN, PhD, FACCCN
Austin Health
RMIT University
Deakin University
Melbourne, Australia

Gina-Marie Barletta, MD
Pediatric Kidney Disease and
Hypertension Centers
Phoenix, Arizona
Jeffrey F. Barletta, PharmD, FCCM
Professor and Vice Chair of
Pharmacy Practice
Midwestern University, College of

Pharmacy-Glendale
Glendale, Arizona
Shriganesh R. Barnela, MD, DNB
Director
Nephron Kidney Care
Consultant Interventional
Nephrologist
United CIIGMA Hospital
Aurangabad, India
Hülya Bayır, MD
Professor of Critical Care Medicine,
Environmental and Occupational
Health
UPMC Endowed Chair in Critical
Care Pediatric Research
University of Pittsburgh
Research Director and Associate
Chief of Pediatric Critical Care
Medicine
Children’s Hospital of Pittsburgh
Associate Director of Center for Free
Radical and Antioxidant Health
and Safar Center for Resuscitation
Research
Pittsburgh, Pennsylvania
Monica Beaulieu, MD, FRCPC, MHA
Clinical Associate Professor
University of British Columbia
Head, Division of Nephrology
Providence Health Care

Vancouver, British Columbia, Canada
Antonio Bellasi, MD
Department of Nephrology and
Dialysis
S.Anna Hospital
Como, Italy

Joanne M. Bargman, MD
Division of Nephrology
University Health Network
University of Toronto
Toronto, Ontario, Canada

vii


viii  
Contributors
Rinaldo Bellomo, MB BS (Hons),
MD, FRACP, FCICM, FAAHMS
Department of Intensive Care
Austin Hospital and Royal
Melbourne Hospital
Australian and New Zealand
Intensive Care Research Centre
School of Public Health and
Preventive Medicine
Monash University and School of
Medicine
The University of Melbourne

MelbourneVictoriaAustralia
François Beloncle, MD
Département de Réanimation
Médicale et de Médecine
Hyperbare
Centre Hospitalier Universitaire
d’Angers
Laboratoire de Biologie
Neurovasculaire et Mitochondriale
Intégrée
Institut Mitovasc
Université d’Angers
Angers, France
Arjun Bhansali, MD
Mount Sinai Hospital
New York, New York
Azra Bihorac, MD, MS
Department of Medicine
University of Florida
Gainesville, Florida
Frederic T. Billings, IV, MD, MSc
Associate Professor of
Anesthesiology and Medicine
Vanderbilt University Medical Center
Nashville, Tennessee
Horst-Walter Birk, MD
Department of Internal Medicine II
Division of Pulmonology,
Nephrology, and Critical Care
Medicine

University Clinic Giessen and
Marburg (UKGM)
Campus Giessen
Giessen, Germany
Luis Ignacio Bonilla-Reséndiz, MD
Department of Nephrology
University Hospital “Dr. José
Eleuterio González”
Autonomous University of Nuevo
León
Monterrey, Mexico
Josée Bouchard, MD, FRCPC
Associate Professor of Medicine
Université de Montréal
Hopital du Sacré-Coeur de Montréal
Montréal, Québec, Canada

Edmund Bourke, MD
Department of Medicine
Veterans Administration Medical
Center
Brooklyn, New York
George Braitberg, FACEM, FACMT
Professor of Emergency Medicine
Director of Emergency Medicine
University of Melbourne
The Royal Melbourne Hospital
Parkville, Victoria, Australia
Alessandra Brendolan, MD
Department of Nephrology, Dialysis

and Transplantation
San Bortolo Hospital
International Renal Research
Institute of Vicenza
Vicenza, Italy
Alessandra Brocca, PhD
Department of Nephrology, Dialysis
and Transplantation
International Renal Research
Institute of Vicenza (IRRIV)
San Bortolo Hospital
Vicenza, Italy
Department of Medicine DIMED
University of Padova Medical School
Padova, Italy
Patrick D. Brophy, MD, MHCDS
The Jean E. Robillard MD, Chair of
Pediatric Nephrology
Professor and Director
Department of Pediatric Nephrology,
Dialysis & Transplantation
Stead Family University of Iowa
Children’s Hospital
University of Iowa
Iowa City, Iowa

Renato Antunes Caires, MD
Sao Paulo State Cancer Institute
University of Sao Paulo
Sao Paulo, Brazil

Pietro Caironi, MD
SCDU Anestesia e Rianimazione
Azienda Ospedaliero-Universitaria
San Luigi Gonzaga
Department of Oncology
University of Turin
Turin, Italy
Roberta Camilla, MD
Nephrology Dialysis and
Transplantation Unit
Regina Margherita Children’s
Hospital
Turin, Italy
Israel Campos, MD
Senior Research Fellow
Renal Research Institute
New York, New York
Bernard Canaud, MD
Emeritus Professor
Montpellier University
UFR Medicine
Montpellier, France
Chief Medical Officer
Centre of Excellence Medical
Bad Homburg, Germany
Vincenzo Cantaluppi, MD
Associate Professor of Nephrology
Chief of Nephrology, Dialysis, and
Kidney Transplantation Unit
Department of Translational

Medicine
University of Eastern Piedmont
Novara, Italy

Richard Bucala, MD, PhD
Department of Internal Medicine
Department of Pathology
Yale University School of Medicine
New Haven, Connecticut

Maria P. Martinez Cantarin, MD
Assistant Professor of Medicine
Division of Nephrology
Thomas Jefferson University
Philadelphia, Pennsylvania

Timothy E. Bunchman, MD
Professor and Director of Pediatric
Nephrology
Departments of Transplantation and
Rheumatology
Children’s Hospital of Richmond at
VCU
Richmond, Virginia

Giovambattista Capasso, MD, PhD,
FERA
Department of Nephrology
University of Campania–Luigi
Vanvitelli

Naples, Italy

Emmanuel A. Burdmann, MD, PhD
Sao Paulo State Cancer Institute
University of Sao Paulo
Sao Paulo, Brazil
Laurence W. Busse, MD
Department of Medicine
Emory University
Atlanta, Georgia

Joseph A. Carcillo, MD
Professor of Critical Care Medicine
and Pediatrics
University of Pittsburgh
Pittsburgh, Pennsylvania
Eleonora Carlesso, Dip. Ing.
Dipartimento di Fisiopatologia
Medico-Chirurgica e dei Trapianti
Università degli Studi di Milano
Milan, Italy


Contributors  ix
Francesco G. Casino, MD
Nephrologist
Dialysis Centre SM2
Potenza, Italy
Giuseppe Castellano, MD
Nephrology, Dialysis, and

Transplantation Unit
Department of Emergency and
Transplantation
University of Bari
Bari, Italy
Matteo Catania, MD
Resident
Department of Radiology
University of Verona
Verona, Italy
Kelly A. Cawcutt, MD, MS
Assistant Professor of Medicine
Department of Infectious Diseases
University of Nebraska Medical Center
Omaha, Nebraska
Jorge Cerda, MD
Department of Medicine
Albany Medical College
Albany, New York
Elliot Charen, MD
Assistant Professor of Medicine
Department of Nephrology
Icahn School of Medicine
New York, New York
Lakhmir S. Chawla, MD
Division of Intensive Care Medicine
Division of Nephrology
Department of Medicine
Veterans Affairs Medical Center
Washington, District of Columbia

Stefano Chiaramonte, MD
Department of Nephrology Dialysis
and Transplantation
San Bortolo Hospital
Vicenza, Italy
Horng-Ruey Chua, MBBS, MMed(Int
Med), FRCP(Edin), FAMS, FASN
Consultant Nephrologist
Department of Medicine
National University Hospital
Singapore
Bruno Cianciaruso, MD
(deceased)
Division of Nephrology and Dialysis
University of Naples Federico II
Naples, Italy
Paola Ciceri, MD
Renal Division
Department of Health Sciences
San Paolo Hospital
University of Milan
Milan, Italy

Jacek Cieslak, MD, FRCPC
Nephrology Resident
Departments of Internal Medicine
and Nephrology
University of British Columbia
Vancouver, British Columbia, Canada
William R. Clark, MD

Davidson School of Chemical
Engineering
Purdue University
West Lafayette, Indiana
Rolando Claure-Del Granado, MD,
FASN
Universidad Mayor de San Simon
School of Medicine–Hospital Obrero
#2
Cochabamba, Bolivia
Anna Clementi, MD
Department of Nephrology and
Dialysis
San Giovanni Di Dio Hospital
Agrigento, Italy
International Renal Research
Institute of Vicenza (IRRIV)
Vicenza, Italy
Ivan N. Co, MD
Clinical Assistant Professor
Department of Emergency Medicine
and Internal Medicine
Division of Emergency Critical Care
and Pulmonary Critical Care
Medicine
University of Michigan
Ann Arbor, Michigan
Fernanda Oliveira Coelho, MD, PhD
Sao Paulo State Cancer Institute
University of Sao Paulo

Sao Paulo, Brazil
Ferruccio Conte, MD
Renal Division
Department of Health Sciences
San Paolo Hospital
University of Milan
Milan, Italy
Howard E. Corey, MD
The Children’s Kidney Center of
New Jersey
Goryeb Children’s Hospital
Morristown, New Jersey
Laura Cosmai, MD
Onco-Nephrology Outpatient Clinic
San Carlo Borromeo Hospital, ASST
Santi Paolo e Carlo
Milan, Italy
Elerson Carlos Costalonga, MD
Sao Paulo State Cancer Institute
University of Sao Paulo
Sao Paulo, Brazil

Andrea Costamagna, MD
Department of Anesthesia and
Critical Care
AOU Città della Salute e della
Scienza di Torino
University of Turin
Turin, Italy
Maria Rosa Costanzo, MD, FACC,

FAHA
Advocate Medical Group
Midwest Heart Specialists
Oak Brook, Illinois
Mario Cozzolino, MD
Renal Division
Department of Health Sciences
San Paolo Hospital
University of Milan
Milan, Italy
Carl H. Cramer II, MD
Mayo Eugenio Litta Children’s
Hospital
Mayo Clinic
Rochester, Minnesota
Paolo Cravedi, MD, PhD
Icahn School of Medicine at Mount
Sinai
New York, New York
Carlo Crepaldi, MD
Department of Nephrology
San Bortolo Hospital
Vicenza, Italy
Jacques Creteur, MD, PhD
Department of Intensive Care
Erasme University Hospital
Université Libre de Bruxelles
Brussels, Belgium
R. John Crew, MD
Assistant Professor of Internal

Medicine
Division of Nephrology
Columbia University Medical Center
New York, New York
Verônica Torres da Costa e Silva,
MD, PhD
Sao Paulo State Cancer Institute
University of Sao Paulo
Sao Paulo, Brazil
Andrew Davenport, MD
Director, Dialysis Research
Centre for Nephrology
Royal Free Hospital
University College London
London, United Kingdom
Andrew R. Davies, MB, BS, FRACP
Deputy Director
Department of Intensive Care,
Alfred Hospital
Melbourne, Victoria, Australia


x  Contributors
Rohit D’Costa, FRACP, FCICM
The Royal Melbourne Hospital
Parkville, Victoria, Australia
Dawson F. Dean, MD
Division of Nephrology
Indiana University School of Medicine
Indianapolis, Indiana

Charlotte Debiais, MD
Intensive Care Unit
Marc Jacquet Hospital
Melun, France
Massimo de Cal, PhD
Department of Nephrology
San Bortolo Hospital
Vicenza, Italy
Paras Dedhia, MD
Instructor of Medicine
Division of Nephrology, Kidney
C.A.R.E. Program
University of Cincinnati
Cincinnati, Ohio
Harm-Jan de Grooth, MD
Department of Intensive Care
Department of Anesthesiology
Research Unit VUmc Intensive Care
(REVIVE)
Amsterdam Cardiovascular Sciences
Amsterdam, the Netherlands
Roberto Dell’Aquila, MD
Department of Nephrology
St. Bassiano Hospital
Bassano del Grappa, Italy
Sergio Dellepiane, MD, PhD
Nephrology, Dialysis, and Kidney
Transplantation Unit
Department of Medical Sciences
University of Torino

Torino, Italy
Richard Phillip Dellinger, MD,
FCCM, FCCP
Department of Medicine
Cooper Medical School of Rowan
University
Camden, New Jersey
Lucia Del Vecchio, MD
Department of Nephrology and
Dialysis
Alessandro Manzoni Hospital
Lecco, Italy
Thomas A. Depner, MD
Emeritus Professor of Medicine
Department of Internal Medicine
Division of Nephrology
University of California, Davis
School of Medicine
Sacramento, California

Silvia De Rosa, MD
Department of Nephrology, Dialysis
and Transplantation
International Renal Research
Institute of Vicenza (IRRIV)
Department of Anesthesia and
Intensive Care
San Bortolo Hospital
Vicenza, Italy
Clifford S. Deutschman, MS, MD,

MCCM
Vice-Chair, Research, Department of
Pediatrics
Professor of Pediatrics and
Molecular Medicine
Hofstra–Northwell School of
Medicine
New Hyde Park, New York;
Professor
Elmezzi Graduate School of
Molecular Medicine
Feinstein Institute for Medical
Research
Manhasset, New York
Prasad Devarajan, MD
Louise M. Williams Endowed Chair
Professor of Pediatrics and
Developmental Biology
Director of Nephrology and
Hypertension
Director, Pediatric Nephrology
Fellowship Program
Co-Director, Office of Pediatric
Clinical Fellowships
Medical Director, Stone Center
Director, NIH Center of Excellence in
Nephrology
CEO, Dialysis Unit
Cincinnati Children’s Hospital
Medical Center

Cincinnati, Ohio
A. Dewitte, MD
Department of Anesthesiology and
Intensive Care II
University of Bordeaux
Bordeaux, France
Biagio R. Di Iorio, MD
Division of Nephrology and Dialysis
The Hospital of Solofra Agostino
Landolfi
Solofra, Italy
Luca Di Lullo, MD
Department of Nephrology and
Dialysis
L. Parodi-Delfino Hospital
Colleferro, Italy
Lucia Di Micco, MD
Division of Nephrology and Dialysis
The Hospital of Solofra Agostino
Landolfi
Solofra, Italy

Matteo Di Nardo, MD
Pediatric Intensive Care Unit
Department of Emergency,
Anesthesia, and Intensive Care
(DEA-ARCO)
Bambino Gesù Children’s Hospital,
IRCCS
Rome, Italy

Xiaoqiang Ding, MD, PhD
Professor
Department of Internal Medicine
Fudan University
Director, Department of Nephrology
Zhongshan Hospital
Fudan University
Shanghai, China
Fiorella D’Ippoliti, MD
Department of Nephrology, Dialysis
and Transplantation
International Renal Research
Institute of Vicenza (IRRIV)
Department of Anesthesia and
Intensive Care
San Bortolo Hospital
Vicenza, Italy
Salvatore Di Somma, MD, PhD
Department of Medical-Surgical
Sciences and Translational
Medicine
University of Rome Sapienza
Rome, Italy
Kent Doi, MD, PhD
Department of Acute Medicine
The University of Tokyo
Tokyo, Japan
David J. Dries, MD
Division Medical Director
HealthPartners Medical Group and

Professor of Surgery
University of Minnesota
Minneapolis, Minnesota
Wilfred Druml, MD
Medical Department III
Division of Nephrology
Vienna General Hospital
Medical University of Vienna
Vienna, Austria
Graeme Duke, MD, FCICM
Box Hill Hospital, Eastern Health
Melbourne, Australia
Francois Durand, MD
Hepatology and Liver Intensive Care
University Paris Diderot
Clichy, France
Michael T. Eadon, MD
Division of Nephrology
Indiana University School of
Medicine
Indianapolis, Indiana


Contributors  xi
Devin Eckstein, DO
The Children’s Kidney Center of
New Jersey
Goryeb Children’s Hospital
Morristown, New Jersey

Fatemeh Fattahi, MD
Department of Pathology
University of Michigan Medical
School
Ann Arbor, Michigan

Moritoki Egi, MD
Department of Anesthesiology
Kobe University Hospital
Hyogo, Japan

Christine Kinggaard Federspiel, MD
Departments of Medicine and
Anesthesia
University of California
San Francisco, California
Department of Anesthesiology
Nordsjællands Hospital
University of Copenhagen
Copenhagen, Denmark

Somchai Eiam-Ong, MD
Division of Nephrology
Department of Medicine
Faculty of Medicine
Chulalongkorn University
King Chulalongkorn Memorial
Hospital
Bangkok, Thailand
Paul W.G. Elbers, MD

Department of Intensive Care
Research Unit VUmc Intensive Care
(REVIVE)
Amsterdam Cardiovascular Sciences
Amsterdam, the Netherlands
Francesca Elli, MD
Renal Division
Department of Health Sciences
San Paolo Hospital
University of Milan
Milan, Italy
Steve Elliott, PhD
Elliott Consulting
Thousand Oaks, California
David R. Emlet, PhD
Research Assistant Professor
Department of Critical Care
Medicine
Center for Critical Care Nephrology
The CRISMA Center
University of Pittsburgh School of
Medicine
Pittsburgh, Pennsylvania
Zoltan Endre, MD
Department of Nephrology
Prince of Wales Hospital and
Clinical School
Sydney, Australia
Roger G. Evans, PhD
Cardiovascular Disease Program

Bioscience Discovery Institute and
Department of Physiology
Monash University
Melbourne, Victoria, Australia
Vito Fanelli, MD, PhD
Department of Anesthesia and
Critical Care
AOU Città della Salute e della
Scienza di Torino
University of Turin
Turin, Italy

Marcela A. Ferrada, MD
National Institutes of Health
Rockville, Maryland
Fiorenza Ferrari, MD, MSc
Department of Anesthesiology and
Intensive Care Medicine
San Bortolo Hospital
Pharmacology Section
International Renal Research
Institute of Vicenza (IRRIV)
Vicenza, Italy
Enrico Fiaccadori, MD, PhD
Renal Intensive Care Unit
Parma University Hospital
Parma, Italy
Marco Fiorentino, MD
Center for Critical Care Nephrology
The CRISMA Center

Department of Critical Care
Medicine
University of Pittsburgh School of
Medicine
Pittsburgh, Pennsylvania
Department of Emergency and Organ
Transplantation
Nephrology, Dialysis, and
Transplantation Unit
University of Bari
Bari, Italy
Caleb Fisher, MD
Liver Intensive Care Unit
Institute of Liver Studies
King College Hospital
London, United Kingdom
Michael F. Flessner, MD, PhD
Medical Director
Frederick Community Action
Agency
Frederick, Maryland
Marco Formica, MD
Nephrology and Dialysis Unit
Medical Department
ASLCN1 Hospitals
Cuneo, Italy

Lui G. Forni, PhD
Department of Intensive Care
Medicine

Royal Surrey County Hospital NHS
Foundation Trust
Surrey Perioperative Anaesthesia
Critical Care Collaborative
Research Group (SPACeR)
Faculty of Health Care Sciences
University of Surrey
Guildford, United Kingdom
Claire Francoz, MD, PhD
Hepatology and Liver Intensive
Care
Hospital Beaujon
Clichy, France
Craig French, MBBS, FCICM,
FANZCA
Director of Intensive Care
Western Health
Clinical Associate Professor
The University of Melbourne
Parkville, Victoria, Australia
Dana Y. Fuhrman, DO, MS
Center for Critical Care Nephrology
Department of Critical Care
Medicine
University of Pittsburgh
Pittsburgh, Pennsylvania
Giordano Fumagalli, MD
Nephrology and Dialysis Unit
USL Toscana Nord Ovest
Versilia Hospital

Lido di Camaiore, Italy
Miriam Galbusera, BiolSciD
Head, Unit of Platelet-Endothelial
Cell Interaction
IRCCS–Istituto di Ricerche
Farmacologiche Mario Negri
Bergamo, Italy
Maurizio Gallieni, MD
Nephrology and Dialysis
ASST Santi Paolo e Carlo
Department of Biomedical and
Clinical Sciences “Luigi Sacco”
University of Milano
Milan, Italy
Hilary S. Gammill, MD
Associate Professor
Department of Obstetrics and
Gynecology
University of Washington
Affiliate Investigator
Fred Hutchinson Cancer Research
Center
Seattle, Washington


xii  
Contributors
Dayong Gao, PhD
Department of Mechanical
Engineering

University of Washington
Seattle, Washington
Francesco Garzotto, MD
Department of Nephrology
Dialysis and Transplantation
International Renal Research
Institute of Vincenza
San Bartolo Hospital
Vicenza, Italy
Giuseppe Gatta, MD
Department of Nephrology and
Dialysis
Casa Sollievo della Sofferenza
Research Hospital
San Giovanni Rontondo, Italy
Kelly R. Genga, MD
Centre for Heart Lung Innovation
St. Paul’s Hospital
University of British Columbia
Vancouver, British Columbia, Canada
Simonetta Genovesi, MD
Department of Medicine and Surgery
University of Milan-Bicocca
Nephrology Unit
San Gerardo Hospital
Monza, Italy
Yuri S. Genyk, MD
Professor of Clinical Surgery
Surgical Director, Liver Transplant
Program

Division of HepatoBiliary
Surgery and Abdominal Organ
Transplantation
Keck School of Medicine
University of Southern California
Los Angeles, California
Christel Geradin, MD
Intensive Care Unit
Marc Jacquet Hospital
Melun, France
Loreto Gesualdo, MD, FERA
Nephrology, Dialysis, and
Transplantation Unit
Department of Emergency and Organ
Transplantation
University of Bari
Bari, Italy
Davide Giavarina, MD
Director of Clinical Laboratory
San Bortolo Hospital
Venice, Italy
Anna Giuliani, MD
Department of Nephrology Dialysis
and Transplantation
San Bortolo Hospital
Vicenza, Italy

Ilya G. Glezerman, MD
Associate Attending Physician
Renal Service

Department of Medicine
Memorial Sloan Kettering Cancer
Center
Associate Professor of Clinical
Medicine
Department of Medicine
Weill Cornell Medical College
New York, New York
Stuart L. Goldstein, MD
Clark D. West Endowed Chair
Director, Center for Acute Care
Nephrology
Cincinnati Children’s Hospital
Medical Center
Cincinnati, Ohio
Thomas A. Golper, MD, FACP, FASN
Professor of Medicine
Department of Nephrology
Vanderbilt University Medical Center
Nashville, Tennessee
Hernando Gómez, MD
The Center for Critical Care
Nephrology
The CRISMA Center
Department of Critical Care
Medicine
University of Pittsburgh
Pittsburgh, Pennsylvania
Antonio Granata, MD
Department of Nephrology

St. Giovanni Di Dio Hospital
Agrigento, Italy
Giuseppe Grandaliano, MD
Nephrology, Dialysis, and
Transplantation Unit
Department of Medical and Surgical
Sciences
University of Foggia
Foggia, Italy
Giacomo Grasselli, MD
Dipartimento di Anestesia
Rianimazione ed Emergenza Urgenza
Fondazione IRCCS Ca’ Granda–
Ospedale Maggiore Policlinico
Milan, Italy
A.B. Johan Groeneveld, MD, PhD
(deceased)
Department of Intensive Care
Erasmus Medical Center
Rotterdam, the Netherlands
Philippe Guerci, MD
Surgical Intensive Care Unit
Department of Anesthesiology and
Intensive Care Medicine
University Hospital of Nancy
Nancy, France

Kyle J. Gunnerson, MD, FCCM
Associate Professor
Departments of Emergency

Medicine, Anesthesiology, and
Internal Medicine
Chief, Division of Emergency Critical
Care
Medical Director, Massey Family
Foundation Emergency Critical
Center (EC3)
Michigan Center for Integrative
Research in Critical Care
(MCIRCC)
University of Michigan Health
System
Ann Arbor, Michigan
Nikolas Harbord, MD
Assistant Professor of Medicine
Department of Nephrology
Icahn School of Medicine
New York, New York
Lyndsay A. Harshman, MD
University of Iowa Stead Family
Department of Pediatrics
Division of Pediatric Nephrology,
Dialysis, and Transplantation
Iowa City, Iowa
Anthony J. Hennessy, MB BCh,
MRCPI
Senior Registrar
Anaesthesia and Intensive Care
Cork University Hospital
Cork, Ireland

Graham L. Hill, MD, FRCS, FRACS,
FACS
(deceased)
Emeritus Professor of Surgery
Faculty of Medical and Health
Sciences
University of Auckland
Auckland, New Zealand
Charles Hobson, MD, MHA
Department of Health Services
Research, Management, and Policy
University of Florida
Gainesville, Florida
Bernd Hohenstein, MD
Nephrological Center
Villingen-Schwenningen
Faculty of Medicine Carl Gustav
Carus
Technische Universitat Dresden
Dresden, Germany
Patrick M. Honoré, MD
Intensive Care Unit Department
Universitair Ziekenhuis Brussel
Vrije Universiteit Brussel
Brussels, Belgium


Contributors  xiii
Edward Horwitz, MD
MetroHealth Medical Center

Assistant Professor of Medicine
Case Western Reserve University
School of Medicine
Cleveland, Ohio
Leila Hosseinian, MD
Department of Anesthesiology
Mount Sinai Hospital
New York, New York
Eric A.J. Hoste, MD, PhD
Department of Intensive Care
Medicine
Ghent University Hospital
Ghent, Belgium
Ghent University, Ghent, Belgium
and Research Foundation–Flanders
Brussels, Belgium
Andrew A. House, MD, MS, FRCPC,
FASN
Professor of Medicine
Chair/Chief Division of Nephrology
Schulich School of Medicine &
Dentistry
London Health Sciences Centre
University Hospital
London, Ontario, Canada
H. David Humes, MD
Professor of Medicine
Division of Nephrology
Department of Internal Medicine
University of Michigan School of

Medicine
Ann Arbor, Michigan
Faeq Husain-Syed, MD
Department of Internal Medicine II
Division of Pulmonology,
Nephrology, and Critical Care
Medicine
University Clinic Giessen and
Marburg (UKGM)
Campus Giessen
Giessen, Germany
Can Ince, PhD
Professor
Department of Intensive Care
Erasmus Medical Center
Erasmus University of Rotterdam
Rotterdam, the Netherlands
Professor
Department of Translational
Physiology
Academic Medical Center
University of Amsterdam
Amsterdam, the Netherlands
Todd S. Ing, MD
Department of Medicine
Stritch School of Medicine
Loyola University Chicago
Maywood, Illinois

Rita Jacobs, MD

Intensive Care Unit Department
Universitair Ziekenhuis Brussel
Vrije Universiteit Brussel
Brussels, Belgium
Dharmvir Jaswal, MD
National Institutes of Health
Rockville, Maryland
Arun Jeyabalan, MD
Associate Professor
Department of Obstetrics,
Gynecology, and Reproductive
Sciences
University of Pittsburgh
Pittsburgh, Pennsylvania
Olivier Joannes-Boyau, MD
Department of Anesthesiology and
Intensive Care II
University of Bordeaux
Bordeaux, France
Michael Joannidis, MD
Professor of Medicine
Division of Intensive Care and
Emergency Medicine
Department of Internal Medicine
Medical University Innsbruck
Innsbruck, Austria
Emily Joyce, MD
Center for Critical Care Nephrology
Department of Pediatrics
University of Pittsburgh School of

Medicine
Pittsburgh, Pennsylvania
Sandra L. Kane-Gill, PharmD, MSc
Associate Professor of Medicine
Department of Pharmacy and
Therapeutics
Department of Critical Care
Medicine
University of Pittsburgh
Pittsburgh, Pennsylvania
Lewis J. Kaplan, MD, FACS, FCCM
Associate Professor of Surgery
Perelman School of Medicine,
University of Pennsylvania
Division of Trauma, Surgical Critical
Care, and Emergency Surgery
Section Chief, Surgical Critical Care
Corporal Michael J. Crescenz VA
Medical Center
Philadelphia, Pennsylvania
Kianoush Kashani, MD
Division of Nephrology and
Hypertension
Division of Pulmonary and Critical
Care Medicine
Department of Medicine
Mayo Clinic
Rochester, Minnesota

Nevin Katz, MD

Division of Cardiac Surgery
Johns Hopkins University
Baltimore, Maryland
John A. Kellum, MD, MCCM
Director, Center for Critical Care
Nephrology
Professor and Vice Chair
Department of Critical Care
Medicine
University of Pittsburgh
Pittsburgh, Pennsylvania
Ramesh Khanna, MD
Karl D. Nolph, MD Chair in
Nephrology
Professor of Medicine
Director
Division of Nephrology
University of Missouri-Columbia,
Columbia, Missouri
Nahmah Kim-Campbell, MD
Assistant Professor of Critical Care
Medicine
Department of Critical Care
Medicine
Children’s Hospital of Pittsburgh of
UPMC
University of Pittsburgh
Pittsburgh, Pennsylvania
Joshua D. King, MD
Division of Nephrology

University of Virginia Health System
Charlottesville, Virginia
Christopher J. Kirwan, MD
William Harvey Institute
Barts and the London School of
Medicine and Dentistry
Queen Mary University of London
Adult Critical Care Unit and
Department of Renal Medicine and
Transplantation
The Royal London Hospital
Barts Health NHS Trust
London, United Kingdom
Joseph E. Kiss, MD
Professor of Medicine
University of Pittsburgh
Pittsburgh, Pennsylvania
David Klein, MD, MBA
Staff Physician
Department of Critical Care
St. Michael’s Hospital
Assistant Professor of Medicine and
Public Health
University of Toronto
Scientist
Li Ka Shing Knowledge Institute
Toronto, Ontario, Canada


xiv  

Contributors
Peter Kotanko, MD, FASN
Research Director
Renal Research Institute
Adjunct Professor of Medicine
Department of Nephrology
Icahn School of Medicine at Mount
Sinai
New York, New York
Raymond T. Krediet, MD, PhD
Professor of Nephrology
Academic Medical Center
University of Amsterdam
Amsterdam, the Netherlands
Martin K. Kuhlmann, MD
Professor of Medicine and
Nephrology
Department of Internal Medicine
Division of Nephrology
Vivantes Klinikum im Friedrichshain
Berlin, Germany
Jan Willem Kuiper, MD, PhD
Intensive Care and Pediatric Surgery
Erasms MC–Sophia Children’s
Hospital
Rotterdam, the Netherlands
Philippe Lachance, MD, MSc,
FRCPC
Nephrologist and Adult Critical Care
Fellow

Department of Critical Care
Medicine
Faculty of Medicine and Dentistry
University of Alberta
Edmonton, Alberta, Canada
Norbert Lameire, MD, PhD
Renal Division
Ghent University Hospital
Ghent, Belgium
Thomas Langer, MD
Department of Pathophysiology and
Transplantation
University of Milan
Milan, Italy
Yugeesh R. Lankadeva, PhD
Florey Institute of Neuroscience and
Mental Health
Melbourne, Victoria, Australia
Louis-Philippe Laurin, MD
Clinical Assistant Professor of
Medicine
University of Montreal
Division of Nephrology
Maisonneuve-Rosemont Hospital
Montréal, Québec, Canada

Elena Lazzeri, MD
Excellence Centre for Research
Transfer and High Education for
the Development of DE NOVO

Therapies (DENOTHE)
Department of Clinical and
Experimental Biomedical Sciences
University of Florence
Florence, Italy
Martine Leblanc, MD
Departments of Nephrology and
Intensive Care
Hôpital Maisonneuve-Rosemont
Montréal, Québec, Canada
Joannie Lefebvre, MD
Assistant Professor of Clinic
Department of Medicine
Nephrology Division
Hôpital Maisonneuve-Rosemont
Université de Montréal
Montréal, Québec, Canada
Paolo Lentini, MD, PhD
Department of Nephrology
St. Bassiano Hospital
Bassano del Grappa, Italy
Hélène Leray-Moragués, MD
Department of Nephrology
Lapeyronie University Hospital
Montpellier, France
Adeera Levin, MD, FRCPC, CM
Professor of Medicine, University of
British Columbia
Head UBC Division of Nephrology
Executive Director BC Provincial

Renal Agency
Vancouver, British Columbia, Canada
Susie Q. Lew, MD
Department of Medicine
George Washington University
Washington, District of Columbia
Helen Liapis, MD
Senior Consultant
Arkana Laboratories
Little Rock, Arkansas
Kathleen D. Liu, MD, PhD
Departments of Medicine and
Anesthesia
University of California
San Francisco, California
Sergio Livigni, MD
Director, Intensive Care Unit
San Giovanni Bosco Hospital
Torino, Italy
Francesco Locatelli, MD
Department of Nephrology and
Dialysis
Manzoni Hospital
Lecco, Italy

Anna Lorenzin, MD
Department of Nephrology, Dialysis
and Transplantation
International Renal Research
Institute of Vincenza (IRRIV)

San Bartolo Hospital
Vicenza, Italy
Jian-Da Lu, MD
Department of Nephrology
Huashan Hospital
Fudan University
Shanghai, China
Renhua Lu, MD
Associate Chief Physician
Department of Nephrology
School of Medicine
Renji Hospital
Shanghai Jiao Tong University
Shanghai, China
Nicholas Lysak, MD
Department of Surgery
University of Florida
Gainesville, Florida
Etienne Macedo, MD, PhD
University of California San Diego
San Diego, California
Niti Madan, MD
Associate Professor of Medicine
Department of Internal Medicine
Division of Nephrology
University of California, Davis
School of Medicine
Sacramento, California
François Madore, MD
Professor of Medicine

Université de Montréal
Montréal, Québec, Canada
Linda L. Maerz, MD
Department of Surgery
Yale University School of Medicine
New Haven, Connecticut
Matthew J. Maiden, MD, PhD
Consultant
Intensive Care Unit
Royal Adelaide Hospital
Adelaide, South Australia, Australia;
University Hospital Geelong
Geelong, Victoria, Australia
Rakesh Malhotra, MD, MPH
University of California San Diego
San Diego, California
Marita Marengo, MD
Nephrology and Dialysis Unit
Azienda Sanitaria Locale CN1
Cuneo, Italy


Contributors  xv
Filippo Mariano, MD
Nephrology, Dialysis and Kidney
Transplantation Unit
Department of Medical Sciences
University of Torino
Torino, Italy

Peter A. McCullough, MD, MPH
Baylor University Medical Center
Baylor Heart and Vascular Institute
Baylor Jack and Jane Hamilton Heart
and Vascular Hospital
Dallas, Texas

Paul E. Marik, MD, FCCM, FCCP
Division of Pulmonary and Critical
Care Medicine
Eastern Virginia Medical School
Norfolk, Virginia

Blaithin A. McMahon, MD, PhD
Assistant Professor of Medicine
Division of Nephrology
Johns Hopkins University School of
Medicine
Baltimore, Maryland

John J. Marini, MD
Professor of Medicine
University of Minnesota
Minneapolis, Minnesota

Ravindra L. Mehta, MD, FASN
University of California San Diego
San Diego, California

Paraish S. Misra, MD

Division of Nephrology
University of Toronto
Toronto, Ontario, Canada
Barry A. Mizock, MD
Department of Medicine
University of Illinois at Chicago
Chicago, Illinois
Jwalant R. Modi, MBBS
Division of Nephrology
Indiana University School of
Medicine
Indianapolis, Indiana
Gilbert Moeckel, MD, PhD
Department of Pathology
Yale University School of Medicine
New Haven, Connecticut

Rossella Marino, MD
Department of Medical-Surgery
Sciences and Translational
Medicine
University of Rome Sapienza
Rome, Italy

Caterina Mele, PhD
IRCCS–Istituto di Ricerche
Farmacologiche Mario Negri
Clinical Research Center for Rare
Diseases Aldo e Cele Daccò
Bergamo, Italy

Mark R. Marshall, MD
Associate Professor
Faculty of Medical and Health
Sciences
School of Medicine
University of Auckland
Auckland, New Zealand

Madhav Menon, MD
Icahn School of Medicine at Mount
Sinai
New York, New York

Bruce A. Molitoris, MD
Distinguished Professor of Medicine
and Integrative and Cellular
Physiology
Division of Nephrology
Indiana University School of
Medicine
Indianapolis, Indiana

Mario Meola, MD, PhD
Researcher
Sant’Anna School of Advanced
Studies
Aggregated Professor of Nephrology
University of Pisa
Pisa, Italy

Santo Morabito, MD
Hemodialysis Unit
Department of Nephrology and
Urology
Umberto I Hospital, Sapienza
University of Rome
Rome, Italy

Aicha Mérouani, MD
Associate Professor of Pediatrics
Pediatric Nephrologist
Division of Pediatric Nephrology
Department of Pediatrics
Sainte Justine Hospital
University of Montreal
Montréal, Québec, Canada

Roberto Pozzi Mucelli, MD
Chief
Department of Radiology
University of Verona
Verona, Italy

Johan Mårtensson, MD, PhD
Section of Anesthesia and Intensive
Care Medicine
Department of Physiology and
Pharmacology
Karolinska Institute

Stockholm, Sweden
Ryo Matsuura, MD
Department of Nephrology and
Endocrinology
The University of Tokyo
Tokyo, Japan
Clive N. May, PhD
Florey Institute of Neuroscience and
Mental Health
Melbourne, Victoria, Australia
Patrizio Mazzone, MD
Cardiothoracic and Vascular
Department
Arrhythmology and Cardiac Pacing
Unit
IRCCS Ospedale San Raffaele
Milan, Italy
Jerry McCauley, MD, MPH
Chief, Division of Nephrology
Professor of Medicine
Thomas Jefferson University
Philadelphia, Pennsylvania

Jean-Yves Meuwly, MD
Associate Professor
Radiology Department
Centre Hospitalier et Universitaire
Vaudois (CHUV)
Lausanne, Switzerland
Paola Milla, BS, PhD

Department of Drug Science and
Technology
University of Turin
Turin, Italy
Madhukar Misra, MD, FRCP(UK),
FASN, FACP
Professor of Clinical Medicine
University of Missouri–Columbia
Columbia, Missouri

Patrick T. Murray, MD, FASN,
FRCPI, FJFICMI
Professor of Medicine
School of Medicine and Medical
Science
University College Dublin
Dublin, Ireland
Raghavan Murugan, MD
Center for Critical Care Nephrology
Department of Critical Care
Medicine
University of Pittsburgh School of
Medicine
Pittsburgh, Pennsylvania
Mitra K. Nadim, MD
Professor of Clinical Medicine
Division of Nephrology and
Hypertension
Keck School of Medicine
University of Southern California

Los Angeles, California


xvi  
Contributors
Devika Nair, MD
Chief Nephrology Fellow
Vanderbilt University Medical Center
Nashville, Tennessee
Federico Nalesso, MD, PhD
Department of Nephrology, Dialysis
and Transplantation
International Renal Research
Institute of Vicenza (IRRIV)
Vicenza, Italy
Mauro Neri, MD
Department of Nephrology, Dialysis
and Transplantation
International Renal Research
Institute of Vicenza (IRRIV)
San Bortolo Hospital
Department of Management and
Engineering
University of Padova
Vicenza, Italy
Trung C. Nguyen, MD
Associate Professor of Pediatrics
Baylor College of Medicine
Texas Children’s Hospital
Houston, Texas

Zhaohui Ni, MD
Department of Nephrology
Ren Ji Hospital
School of Medicine
Shanghai Jiao Tong University
Shanghai, China
Marina Noris, PhD
IRCCS–Istituto di Ricerche
Farmacologiche Mario Negri
Clinical Research Center for Rare
Diseases Aldo e Cele Daccò
Bergamo, Italy
Tessa Novick, MD
Nephrology Fellow
Division of Nephrology
Johns Hopkins University School of
Medicine
Baltimore, Maryland
John C. O’Horo, MD, MPH
Senior Associate Consultant
Assistant Professor of Medicine
Divisions of Infectious Diseases
and Pulmonary and Critical Care
Medicine
Mayo Clinic College of Medicine
Rochester, Minnesota
Mark Douglas Okusa, MD
Division of Nephrology and Center
of Immunity and Regenerative
Medicine

University of Virginia
Charlottesville, Virginia

Steven M. Opal, MD
Professor of Medicine
Infectious Disease Division
Rhode Island Hospital
Alpert Medical School of Brown
University
Providence, Rhode Island
Helen Ingrid Opdam, FRACP,
FCICM
The Austin Hospital
Heidelberg, Victoria, Australia
Marlies Ostermann, PhD, MD, FRCP
Consultant in Critical Care and
Nephrology
King’s College London
Department of Critical Care
Medicine
Guy’s and St. Thomas’ Foundation
Hospital
London, United Kingdom
Emerenziana Ottaviano, MD
Renal Division
Department of Health Sciences
San Paolo Hospital
University of Milan
Milan, Italy
Heleen M. Oudemans-van Straaten,

MD, PhD
Department of Adult Intensive Care
VU University Medical Centre
Amsterdam, the Netherlands
Christian Overgaard-Steensen, MD,
PhD
Department of Intensive Care
Rigshospitalet
Copenhagen, Denmark
Massimo A. Padalino, MD, PhD
Assistant Professor of Cardiac
Surgery
Unit of Pediatric and Congenital
Cardiovascular Surgery
Department of Cardiac, Thoracic,
and Vascular Sciences
University of Padova
Padova, Italy

Samir S. Patel, MD
The Veterans Affairs Medical Center
George Washington University
Medical Center
Washington, District of Columbia
Didier Payen, MD, PhD
Professor of Anesthesiology and
Critical Care
Groupe Hospitalier Lariboisère
Saint-Louis
Paris, France

Federico Pea, MD
Institute of Clinical Pharmacology
Santa Maria della Misericordia
University Hospital
ASUIUD
Department of Medicine
University of Udine
Udine, Italy
W. Frank Peacock, MD
Department of Emergency Medicine
Baylor College of Medicine
Houston, Texas
Sandrica Young Peart, MBBS, DM
Paeds
Pediatric Nephrology Fellow
Montreal Children’s Hospital
McGill University Health Centre
Montréal, Québec, Canada
Sadudee Peerapornratana, MD
Division of Nephrology
Department of Medicine
Faculty of Medicine
Chulalongkorn University
King Chulalongkorn Memorial
Hospital
Bangkok, Thailand
Paolo Pelosi, MD
IRCCS AOU San Martino–IST
Department of Surgical Sciences and
Integrated Diagnostics

University of Genoa
Genoa, Italy

Vincenzo Panichi, MD
Nephrology and Dialysis Unit
USL Toscana Nord Ovest
Versilia Hospital
Lido di Camaiore, Italy

Zhi-Yong Peng, MD, PhD
Department of Critical Care
Medicine
Zhongnan Hospital
Wuhan University School of
Medicine
Wuhan, China

Priyanka Parameswaran, BS
Research Associate
Nephrology and Hypertension
Cincinnati Children’s Hospital
Medical Center
Cincinnati, Ohio

Norberto Perico, MD
IRCCS–Istituto di Ricerche
Farmacologiche Mario Negri
Clinical Research Center for Rare
Diseases Aldo e Cele Daccò
Bergamo, Italy

Contributors  xvii
Licia Peruzzi, MD
Nephrology, Dialysis and
Transplantation Unit
Regina Margherita Children’s
Hospital
Turin, Italy
Francesco Pesce, MD, PhD
Nephrology, Dialysis and
Transplantation Unit
Department of Emergency and Organ
Transplantation
University of Bari
Bari, Italy
Antonio Pesenti, MD
Dipartimento di Anestesia
Rianimazione ed Emergenza Urgenza
Fondazione IRCCS Ca’ Granda–
Ospedale Maggiore Policlinico
Dipartimento di Fisiopatologia
Medico-Chirurgica e dei Trapianti
Università degli Studi di Milano
Milan, Italy
Ilaria Petrucci, MD, PhD
Temporary Research Fellow
Department of Nephrology
Sant’Anna School of Advanced
Studies

Pisa, Italy
Phuong-Chi Pham, MD, FASN
Chief, Division of Nephrology and
Hypertension
Nephrology Fellowship Training
Program Director
Olive View-UCLA Medical Center
Clinical Professor of Medicine
David Geffen School of Medicine at
UCLA
Sylmar, California
Phuong-Thu Pham, MD, FASN
Clinical Professor of Medicine
Director of Outpatient Services
Kidney Transplant Program
Department of Medicine, Nephrology
Division
David Geffen School of Medicine at
UCLA
Los Angeles, California
Richard K.S. Phoon, FRACP
Centre for Transplantation and
Research
University of Sydney
Department of Renal Medicine
Westmead, Australia
Salvatore Piano, MD
Unit of Internal Medicine and
Hepatology
Department of Medicine

University of Padova
Padova, Italy

Michael R. Pinsky, MD
Professor of Critical Care Medicine
University of Pittsburgh
Pittsburgh, Pennsylvania
Lise Piquilloud, MD
Département de Réanimation
Médicale et de Médecine
Hyperbare
Centre Hospitalier Universitaire
d’Angers
Angers, France
Valentina Pistolesi, MD, PhD
Hemodialysis Unit
Department of Nephrology and
Urology
Umberto I Hospital, Sapienza
University of Rome
Rome, Italy
Lindsay D. Plank, DPhil, MSc
Associate Professor
Department of Surgery
Faculty of Medical and Health
Sciences
University of Auckland
Auckland, New Zealand
Frans B. Plötz, MD, PhD
Department of Pediatrics

Tergooi Hospital
Blaricum, the Netherlands
Manuel Alfredo Podestá, MD
Resident in Nephrology
University of Milan
Milan, Italy
ASST Papa Giovanni XXIII
Bergamo, Italy
Camillo Porta, MD
Medical Oncology
IRCCS San Matteo University
Hospital Foundation
Pavia, Italy
Marco Pozzato, MD
AKI Team Leader
Nephrology and Dialysis Unit
San Giovanni Bosco Hospital
Torino, Italy
Michele Prencipe, MD
Department of Nephrology and
Dialysis
Casa Sollievo della Sofferenza
Research Hospital
San Giovanni Rontondo, Italy

John R. Prowle, MD
William Harvey Institute
Barts and the London School of
Medicine and Dentistry
Queen Mary University of London

Adult Critical Care Unit and
Department of Renal Medicine and
Transplantation
The Royal London Hospital
Barts Health NHS Trust
London, United Kingdom
Zudin A. Puthucheary, MD
Critical Care Consultant
Royal Brompton Hospital
London, United Kingdom
Lirong Qu, MD, PhD
Associate Professor of Pathology
University of Pittsburgh
Pittsburgh, Pennsylvania
Jean-Sebastien Rachoin, MD, FASN
Department of Medicine
Cooper Medical School of Rowan
University
Camden, New Jersey
Jai Radhakrishnan, MD
Professor of Medicine
Division of Nephrology
Department of Medicine
Columbia University Medical Center
Associate Division Chief for Clinical
Affairs
Division of Nephrology
New York Presbyterian Hospital
New York, New York
V. Marco Ranieri, MD

Department of Anesthesia and
Critical Care
Ospedale Policlinico Umberto I
Sapienza
University of Rome
Rome, Italy
Ranistha Ratanarat, MD
Fellow
Department of Nephrology, Dialysis
and Transplantation
San Bortolo Hospital
Vicenza, Italy
Instructor
Department of Medicine
Faculty of Medicine Siriraj Hospital
Mahidol University
Bangkok, Thailand


xviii  
Contributors
Giuseppe Remuzzi, MD
IRCCS–Istituto di Ricerche
Farmacologiche Mario Negri
Clinical Research Center for Rare
Diseases Aldo e Cele Daccò
Ranica, Bergamo, Italy
Unit of Nephrology and Dialysis
Azienda Socio-Sanitaria Territoriale
Papa Giovanni XXIII

Bergamo, Italy

Eric Roessler, MD
Assistant Professor
Nephrology Department
Pontificia Universidad Católica de
Chile Medical School
Chief, Acute Dialysis Unit
Clinical Hospital
Pontificia Universidad Católica de
Chile
Santiago, Chile

Shelby Resnick, MD
Perelman School of Medicine,
University of Pennsylvania
Division of Trauma, Surgical Critical
Care and Emergency Surgery
Philadelphia, Pennsylvania

Paola Romagnani, MD
Excellence Centre for Research
Transfer and High Education for
the Development of DE NOVO
Therapies (DENOTHE)
Department of Clinical and
Experimental Biomedical Sciences
University of Florence
Nephrology Unit
Meyer’s Children’s University

Hospital
Florence, Italy

Oleksa G. Rewa, MD
Critical Care Medicine
Faculty of Medicine and Dentistry
University of Alberta
Edmonton, Alberta, Canada
Zaccaria Ricci, MD
Department of Cardiology and
Cardiac Surgery
Pediatric Cardiac Intensive Care Unit
Bambino Gesù Children’s Hospital,
IRCCS
Rome, Italy
Christophe Ridel, MD
Service de Nephrologie et
d’Aphérèse
AURA Plaisance
Paris, France
Kinan Rifai, MD
Department of Gastroenterology
Städtisches Klinikum Wolfenbüttel
Wolfenbüttel, Germany
Troels Ring, MD
Department of Nephrology
Aalborg Hospital
Aalborg, Denmark
Lilia M. Rizo-Topete, MD
Department of Nephrology, Dialysis

and Transplantation
International Renal Research
Institute of Vicenza (IRRIV)
San Bortolo Hospital
Vicenza, Italy;
Department of Nephrology
University Hospital–José Eleuterio
González
Monterrey, Mexico

Stefano Romagnoli, MD
Department of Cardiac and Vascular
Anesthesia and Post-Surgical
Intensive Care Unit
Careggi Hospital
Florence, Italy
Claudio Ronco, MD
Department of Nephrology, Dialysis
and Transplantation
International Renal Research
Institute of Vicenza (IRRIV)
San Bortolo Hospital
Vicenza, Italy
Federico Ronco, MD
Interventional Cardiology
Cardiothoracic and Vascular
Department
AULSS-3 Serenissima
Venezia and Mestre, Italy
Mitchell H. Rosner, MD

Division of Nephrology
University of Virginia Health System
Charlottesville, Virginia
Emanuele Rossetti, MD
Pediatric Intensive Care Unit
Department of Emergency,
Anesthesia and Intensive Care
(DEA-ARCO)
Bambino Gesú Children’s Hospital,
IRCCS
Rome, Italy
James A. Russell, MD
Principal Investigator
Centre for Heart Lung Innovation
Division of Critical Care Medicine
St. Paul’s Hospital
University of British Columbia
Vancouver, British Columbia, Canada

Georges Saab, MD
MetroHealth Medical Center
Associate Professor of Medicine
Case Western Reserve University
School of Medicine
Cleveland, Ohio
Alice Sabatino, MD, MSc
Renal Intensive Care Unit
Parma University Hospital
Parma, Italy
Sonali S. Saboo, DMRD, DNB

Director
Nephron Kidney Care
Consultant Radiologist
United Ciigma Hospital
Aurangabad, India
Sara Samoni, MD
Department of Nephrology, Dialysis
and Transplantation
International Renal Research
Institute of Vicenza (IRRIV)
San Bortolo Hospital
Vicenza, Italy;
Institute of Life Sciences
Sant’Anna School of Advanced
Studies
Pisa, Italy
Penny Lynn Sappington, MD
Associate Professor
Department of Critical Care
Medicine
University of Pittsburgh
Pittsburgh, Pennsylvania
Marco Sartori, PharmD, PhD
Pharmacology Section
International Renal Research
Institute of Vicenza (IRRIV)
Vicenza, Italy;
Department of Pharmaceutical and
Pharmacological Science
University of Padua

Padua, Italy
Judy Savige, MD
Department of Medicine
Royal Melbourne Hospital
University of Melbourne
Melbourne, Australia
Francesco Paolo Schena, MD
Emeritus Professor of Nephrology
University of Bari
Bari, Italy
Antoine Guillaume Schneider, MD,
PhD
Adult Intensive Care Unit
Centre Hospitalier et Universitaire
Vaudois (CHUV)
Lausanne, Switzerland


Contributors  xix
Pieter Schraverus, MD
Department of Anesthesiology
Department of Intensive Care
Research Unit VUmc Intensive Care
(REVIVE)
Amsterdam Cardiovascular Sciences
Amsterdam, the Netherlands
Wibke Schulte, MD
Department of Surgery
Yale University School of Medicine
New Haven, Connecticut

Giuseppe Segoloni, MD
Professor of Nephrology
Nephrology, Dialysis and Kidney
Transplantation Unit
Department of Medical Sciences
University of Torino
Torino, Italy
Matthew W. Semler, MD
Assistant Professor
Division of Allergy, Pulmonary, and
Critical Care Medicine
Vanderbilt University Medical Center
Nashville, Tennessee
Aashish Sharma, DNB
Department of Nephrology and Renal
Transplant Medicine
Fortis Escort Hospitals
Punjab, India
Andrew Shaw, MB, FRCA, FFICM,
FCCM
Professor and Executive Vice Chair
Department of Anesthesiology
Executive Medical Director,
Perioperative Services
Vanderbilt University Medical Center
Nashville, Tennessee
Naitik Sheth, MD
Hackensack University Medical
Center
Hackensack, New Jersey

Ashutosh Shukla, MD
North Florida/South Georgia Veteran
Healthcare System
Division of Nephrology,
Hypertension, and Transplantation
Department of Internal Medicine
University of Florida
Gainesville, Florida
Eric C. Siddall, MD
Assistant Clinical Professor of
Medicine
Columbia University Medical Center
New York, New York

Theodore M. Sievers, PharmD
Clinical Transplant Pharmacist
Ronald Reagan UCLA Medical
Center
Los Angeles, California
Edward D. Siew, MD
Associate Professor of Medicine
Vanderbilt Center for Kidney Disease
(VCKD) and Integrated Program for
AKI (VIP-AKI)
Nashville, Tennessee
Kai Singbartl, MD, MPH, FCCM
Department of Critical Care
Medicine
Mayo Clinic
Rochester, Minnesota

Mervyn Singer, MD
Professor of Intensive Care Medicine
Bloomsbury Institute of Intensive
Care Medicine
University College London
London, United Kingdom
Pooja Singh, MD
Medical Director, Kidney Pancreas
Transplantation
Medical Director, Living Donor
Kidney Transplant Program
Associate Professor of Medicine,
Division of Nephrology
Thomas Jefferson University
Philadelphia, Pennsylvania
Loren E. Smith, MD, PhD
Assistant Professor of Anesthesiology
Vanderbilt University Medical Center
Nashville, Tennessee
Sachin S. Soni, MD, DNB
Director
Nephron Kidney Care
Consultant Interventional
Nephrologist
United Ciigma Hospital
Aurangabad, India
Mara Serrano Soto, MD
Department of Nephrology, Dialysis
and Transplantation
International Renal Research

Institute of Vicenza (IRRIV)
San Bortolo Hospital
Vicenza, Italy;
Servicio de Nefrología
Hospital Universitario Marqués de
Valdecilla
Santander, Spain
Herbert D. Spapen, MD
Intensive Care Unit Department
Universitair Ziekenhuis Brussel
Vrije Universiteit Brussel
Brussels, Belgium

Nattachai Srisawat, MD
Division of Nephrology
Department of Medicine
Faculty of Medicine
Chulalongkorn University
King Chulalongkorn Memorial
Hospital
Bangkok, Thailand;
Center for Critical Care Nephrology
The CRISMA Center
University of Pittsburgh School of
Medicine
Pittsburgh, Pennsylvania
Ajay Srivastava, MD, FASN
Associate Professor of Medicine
Program Director, Nephrology
Fellowship

Division of Nephrology, Kidney
C.A.R.E. Program
University of Cincinnati
Cincinnati, Ohio
Giovanni Stellin, MD
Professor of Cardiac Surgery
Unit of Pediatric and Congenital
Cardiovascular Surgery
Department of Cardiac, Thoracic,
and Vascular Sciences
University of Padova
Padova, Italy
Jordan M. Symons, MD
Department of Pediatrics
University of Washington School of
Medicine
Division of Nephrology
Seattle Children’s Hospital
Seattle, Washington
Balazs Szamosfalvi, MD
Clinical Associate Professor of
Medicine
Division of Nephrology
Department of Internal Medicine
University of Michigan
Ann Arbor, Michigan
Kian Bun Tai, MBChB, MRCP,
FHKAM
Honorary Clinical Assistant
Professor

Department of Medicine and
Therapeutics
Chinese University of Hong Kong
Associate Consultant
Department of Medicine
Alice Ho Miu Ling Nethersole
Hospital
Hong Kong, China
Unmesh V. Takalkar, MS
Consultant Surgeon
United Ciigma Hospital
Associate Professor
Surgical Oncology
Government Cancer Hospital
Aurangabad, India


xx  Contributors
Isaac Teitelbaum, MD
Professor of Medicine
University of Colorado School of
Medicine
Denver, Colorado
Ciro Tetta, MD
Unicyte AG
Oberdorf, Switzerland
Charuhas V. Thakar, MD
Professor of Medicine
Director, Division of Nephrology,
Kidney C.A.R.E. Program

University of Cincinnati
Chief, Section of Nephrology
Cincinnati VA Medical Center
Cincinnati, Ohio
Marta Tonon, MD
Unit of Internal Medicine and
Hepatology
Department of Medicine
University of Padova
Padova, Italy
Francesco Trepiccione, MD, PhD
Department of Nephrology
University of Campania–Luigi
Vanvitelli
Naples, Italy
Darrell Triulzi, MD
Professor of Pathology
University of Pittsburgh
Pittsburgh, Pennsylvania
Chopra Tushar, MD
Division of Nephrology and Center
of Immunity and Regenerative
Medicine
University of Virginia
Charlottesville, Virginia
Shigehiko Uchino, MD
Associate Professor
Department of Anesthesiology
Staff Specialist
Intensive Care Unit

Jikei University school of Medicine
Tokyo, Japan
Ali Valika, MD, FACC
Advocate Medical Group—Midwest
Heart Specialists
Oak Brook, Illinois
Wim Van Biesen, MD, PhD
Renal Division
Ghent University Hospital
Ghent, Belgium
Wim Vandenberghe, MD
Department of Intensive Care
Medicine
Ghent University Hospital
Ghent, Belgium

Raymond Vanholder, MD, PhD
Renal Division
Ghent University Hospital
Ghent, Belgium
Jill Vanmassenhove, MD, PhD
Renal Division
Ghent University Hospital
Ghent, Belgium
Anton Verbine, MD
Department of Nephrology
Conemaugh Health System
Johnstown, Pennsylvania
Marco Vergano, MD
Department of Anesthesia and

Intensive Care
S. Giovanni Bosco Hospital
Torino, Italy
Gianluca Villa, MD
Department of Nephrology, Dialysis
and Transplantation
International Renal Research
Institute of Vicenza (IRRIV)
San Bortolo Hospital
Vicenza, Italy;
Department of Health Science
Section of Anesthesiology and
Intensive Care
University of Florence
Department of Anesthesiology and
Intensive Care
Azienda Ospedaliero Universitaria
Careggi
Florence, Italy
Pierre-Marc Villeneuve, MD
Department of Critical Care
Medicine
Faculty of Medicine and Dentistry
University of Alberta
Edmonton, Alberta, Canada
Jean-Louis Vincent, MD, PhD
Department of Intensive Care
Erasme University Hospital
Université Libre de Bruxelles
Brussels, Belgium

Christophe Vinsonneau, MD, MSc
Intensive Care Unit
Marc Jacquet Hospital
Melun, France
Grazia Maria Virzì, Bsc
Department of Nephrology, Dialysis
and Transplantation
International Renal Research
Institute of Vicenza (IRRIV)
San Bortolo Hospital
Vicenza, Italy

Federico Visconti, MD
Department of Anesthesiology and
Critical Care
San Bartolo Hospital
Vicenza, Italy
Ravindran Visvanathan MBBS,
FRCP (Edin)
Consultant Nephrologist
Hospital Kuala Lumpur
Kuala Lumpur, Malaysia
Li Van Vong, MD
Intensive Care Unit
Marc Jacquet Hospital
Melun, France
Hans-Dieter Walmrath, MD
Department of Internal Medicine II
Division of Pulmonology,
Nephrology, and Critical Care

Medicine
University Clinic Giessen and
Marburg (UKGM)
Campus Giessen
Giessen, Germany
Peter A. Ward, MD
Department of Pathology
University of Michigan Medical
School
Ann Arbor, Michigan
Matthew A. Weir, MD
Department of Medicine
Schulich School of Medicine and
Dentistry
Western University
London, Ontario, Canada
Xiaoyan Wen, MD
Center for Critical Care Nephrology
The CRISMA Center
University of Pittsburgh School of
Medicine
Pittsburgh, Pennsylvania
Julia Wendon, MD
Liver Intensive Care Unit
Institute of Liver Studies
King College Hospital
London, United Kingdom
James Frank Winchester, MD
Professor of Medicine
Department of Nephrology

Icahn School of Medicine
New York, New York
Adrian Wong, PharmD, MPH
Fellow, Outcomes Research and
Pharmacy Informatics
Division of General Internal
Medicine and Primary Care
Brigham and Women’s Hospital
Boston, Massachusetts


Contributors  xxi
Elke L. Woodhouse, MBBS
Centre for Transplantation and Renal
Research
University of Sydney
Department of Renal Medicine
Westmead Hospital
Westmead, Australia

Marta Zaccaria, MD
Department of Nephrology, Dialysis
and Transplantation
International Renal Research
Institute of Vicenza (IRRIV)
San Bortolo Hospital
Vicenza, Italy

Jun Xue, MD
Department of Nephrology

Huashan Hospital
Fudan University
Shanghai, China

Miriam Zacchia, MD, PhD
Department of Nephrology
University of Campania–Luigi
Vanvitelli
Naples, Italy

Anju Yadav, MD
Assistant Professor, Nephrology
Thomas Jefferson University
Philadelphia, Pennsylvania

Teena P. Zachariah, MD
Division of Nephrology
Columbia University Medical
Center
New York, New York

Preethi Yerram, MD
Associate Professor of Clinical
Medicine
University of Missouri–Columbia
Columbia, Missouri
Lenar Yessayan, MD
Clinical Associate Professor of
Medicine
Division of Nephrology

Department of Internal Medicine
University of Michigan
Ann Arbor, Michigan
Jane Y. Yeun, MD
Staff Nephrologist
Sacramento Veterans Administration
Medical Center
Mather, California
Health Sciences Professor of
Medicine
Department of Internal Medicine
Division of Nephrology
University of California, Davis
School of Medicine
Sacramento, California
Alex W. Yu, MD
Honorary Clinical Professor
Department of Medicine and
Therapeutics
Chinese University of Hong Kong
Chief-of-Service and Consultant
Physician
Department of Medicine
Alice Ho Miu Ling Nethersole
Hospital
Hong Kong, China

Michael Zappitelli, MD
Pediatric Nephrologist
Associate Professor

Montreal Children’s Hospital
McGill University Health Centre
Montréal, Québec, Canada
Jose J. Zaragoza, MD
Intensive Care Unit
Hospital Español
Mexico City, Mexico
Alexander Zarbock
Departments of Anesthesiology,
Intensive Care, and Pain Medicine
University Hospital Münster
Münster, Germany

Nereo Zamperetti, MD
Pain Therapy Unit
Vicenza, Italy

Marta Zaroccolo, MD
Nuclear Medicine Physician
Department of Nuclear Medicine
Ospedale San Bortolo
Vicenza, Italy

Fernando G. Zampieri, MD
Research Institute, HCor–Hospital do
Coração
Intensive Care Unit
Hospital Alemão Oswaldo Cruz
São Paulo, Brazil

Han Zhang, MD
Attending Physician
Department of Nephrology
Zhongshan Hospital
Fudan University
Shanghai, China

Pierluigi Zanco, MD
Director
Department of Nuclear Medicine
Ospedale San Bortolo–ULSS 8
Berica
Vicenza, Italy

Andrea Zimmer, MD
Assistant Professor
Division of Infectious Diseases
University of Nebraska Medical
Center
Omaha, Nebraska

Alberto Zanella, MD
Dipartimento di Anestesia
Rianimazione ed Emergenza Urgenza
Fondazione IRCCS Ca’ Granda–
Ospedale Maggiore Policlinico
Dipartimento di Fisiopatologia
Medico-Chirurgica e dei Trapianti
Università degli Studi di Milano
Milan, Italy

Luca Zanoli, MD, PhD
Department of Internal Medicine
University of Catania
Catania, Italy


Preface
Critical care nephrology is a new discipline formally born
in 1998 from a group of scientists and physicians who
established its definition as a multidisciplinary branch of
medicine dealing with issues at the crossroad of intensive
care medicine and nephrology. The discipline became established thanks to a growing appreciation of the importance
of this field, an expanding body of laboratory and clinical
research in this area, editorials (C Ronco, R Bellomo:
Critical Care Nephrology: the time has come. Nephrol Dial
Transplant, 13, 264-267, 1998), International Congresses
(First-, Second, and Third International Courses on Critical
Care Nephrology, Vicenza Italy, 1998-2001-2004 and 2007),
and the first dedicated textbook (Critical Care Nephrology,
Kluwer Academic Publishers, 1998). This book, unique in
its nature, reach, and content, was well received by the
scientific and clinical community. Now, 20 years after the
first edition, we are pleased to present the third edition,
enriched, updated, and expanded to take into account the
very large body of work carried out in the 10 years since
the last edition.
The unrelenting advance of medical progress opens
new areas of interest and opportunity. Such areas must
be explored and explained by experts with appropriate
reference tools and information sources to help clinicians

practice at the very best level. Thus, after much clinical and
experimental research experience in the field of critical care
medicine and nephrology, we have decided to undertake
the effort of producing a third and revised edition of a book
dealing with this subject. Common guidelines, standardized approaches, and appropriate literature dealing with a
multidisciplinary approach to kidney diseases in critically
ill patients are emerging and growing significantly. Internists,
surgeons, critical care physicians, and nephrologists all
treat critically ill patients with acute kidney injury and
the multiple system organ dysfunction syndromes. The
approach varies from hospital to hospital and often within
hospitals. It depends on the structure of the institution, the
tradition of the medical school, the financial status of the
facility, and the heterogeneity of training and experience of
clinicians. Doctors from different fields write notes without
searching for a common multidisciplinary approach to the
patient. Often, they hardly meet at the bedside and various
prescriptions are made in absence of a common decisionmaking process.
A comprehensive review of the state of the art on this
matter is definitely needed in both academic and clinical
medicine. Critical Care Nephrology should provide such a
comprehensive review. It will inevitably become a useful
reference tool for both nephrologists and intensivists. The
title Critical Care Nephrology has been chosen to stress the
aim of the book: to provide a comprehensive and state-of-the
art description and understanding of the problems related
to kidney diseases and blood purification in critically ill
patients. This review includes the pathophysiological
foundations of major syndromes, the basis of laboratory
investigations pertinent to this field, clinical approaches to

complex patient management, interactions between renal
and other organ system failure, monitoring techniques,
therapeutic interventions, supportive treatments, new and
advanced blood purification technologies, and the principles
of management for various relevant derangements. The

title is also intended to draw the reader’s attention to the
multidisciplinary nature of this complex subject matter
and to the need for maximal cooperation between experts
in intensive care and nephrology.
The book focuses on key aspects of the basic sciences
as they pertain to this field. Experimental research and
evidence-based concepts are also discussed. Then, all
relevant clinical syndromes with particular attention to
pathophysiology, diagnosis, and clinical care are treated.
Finally, diagnostic tools and the application of technology
to therapeutical strategies and future trends are detailed.
Critical Care Nephrology deals with general information,
definitions of critical illness, epidemiology, monitoring and
diagnostic procedures, pathophysiology of organ systems in
relation to kidney function, concepts of renal physiological
and pathological responses to various derangements, oxygen
transport and cardiovascular adaptations, hemodynamic
parameters, respiratory parameters, mechanical ventilation
and cardiac support, and severity score parameters as they
relate to the complex care of patients with kidney injury or
the requirement of advanced blood purification technology.
This book is also devoted to all forms of acute kidney injury,
with specific reference to intensive care patients. Prerenal,
renal, and postrenal acute kidney injury is discussed in

terms of etiology, frequency, mechanisms, pathophysiology,
tissue lesions, biopsy patterns, diagnostic procedures, and
management. The nature of the multiple organ dysfunction
syndrome is discussed, with special emphasis on the impact
of different organs’ dysfunction and kidney injury. Kidney
function and acute kidney injury in patients with kidney,
liver, and heart transplants are also discussed in detail, as is
acute illness occurring in long-term hemodialysis patients.
Finally, issues related to special patients such as children,
diabetics, and elderly subjects are carefully analyzed in a
specific session offering an important reference to pediatric
critical care nephrology specialists.
Special emphasis has been placed on diagnosis and
therapeutic interventions and treatment procedures. The
role and significance of novel biomarkers of acute kidney
injury are discussed. Different forms of extracorporeal organ
support are discussed in detail, including liver, lung, and
cardiac support. Artificial renal support is conceived and
discussed first in terms of preventive measures to avoid
renal failure and then as supportive treatment to replace
renal function in different conditions. Thus, the use and
pharmacokinetics of drugs in the critically ill patient are
thoroughly explored. Various forms of extracorporeal
therapies are discussed in detail, including hemodialysis,
hemofiltration, hemoperfusion, and extracorporeal membrane
oxygenation. Mechanical ventilation, mechanical cardiac
support, and the total artificial heart are discussed in relation
to kidney function. Recent advances in the therapy of the
sepsis syndrome are presented, and new insights on future
trends in terms of extracorporeal treatments are provided.

Replacement of renal function by dialysis has been
carried out for many years in both acute and chronic renal
failure patients. The use of continuous renal replacement
techniques has permitted new achievements in the correction
of the metabolic and clinical derangements observed in
critically ill patients. Today, extracorporeal techniques seem
to display important beneficial effects that may overcome
xxiii


xxiv  
Preface
the classic indications of urea removal and fluid regulation.
For this reason, a series of new techniques is appearing on
the scene, with the specific aim of designing a treatment
suitable for patients with multiple organ failure. Selective
removal of cytokines and pro-inflammatory mediators,
plasma adsorption, and other techniques have been used
in vitro, in animal models, and sometimes in patients. There
is a need to summarize all the current experience in the
field and to deliver a comprehensive review of most of
the experimental and clinical work carried out so far. We
believe this book achieves such a goal.
The multidisciplinary nature of the subject and the
rapid evolution of the knowledge in the field make this
third revised edition necessary. Because of its uniqueness,
we believe this book will become a “classic” in the field
as did its predecessor and will be an important reference
tool for nephrologists and intensive care specialists. It is
no coincidence that the editors of the book are themselves

specialists in these particular fields and are strategically
located throughout the world.
In conclusion, the aim of this book is to provide a comprehensive and educational review of the field of critical
care nephrology. Critical Care Nephrology aims to create
a complete reference book for colleagues who are dealing
every day with critically ill patients suffering from kidney
diseases, electrolyte and metabolic imbalances, poisoning,
severe sepsis, major organ dysfunction, and other pathological events that require a multidisciplinary approach, a deep
knowledge of extracorporeal organ support techniques, and
a deep understanding of human knowledge in this field.

The book seeks to facilitate the process of developing
common definitions and approaches to patient management
in nephrology and critical care medicine, so that physicians
think the same way and speak the same language. As such,
it aims to present a comprehensive review of the recent
evolution of the indications, applications, and mechanisms
of function of the most recent extracorporeal techniques
both for the treatment of acute renal failure and for the
management of related disorders in the critically ill patient.
Given these premises, the book may also be helpful for
residents, fellows, and advanced trainees in nephrology
and critical care medicine, as well as for staff physicians
and members of the academic and scientific community
involved in practice and research in the field of critical
care nephrology.
We are grateful to all contributors who made this book
possible and to Dr. Anna Saccardo for her contribution to
the book, her invaluable assistance to the management of
chapters, and the continuous contact and support to the

authors and editors. We especially thank the editorial team
at Elsevier who managed the production of the book with
great professionalism and enthusiasm. We hope our readers
will find that this effort has been worth it and sincerely
hope that it will contribute to improving the care of acutely
ill patients worldwide.

/>
Claudio Ronco
Rinaldo Bellomo
John A. Kellum
Zaccaria Ricci


SECTION 1

Principles of Critical Care
CHAPTER 1 

The Critically Ill Patient
Jean-Louis Vincent and Jacques Creteur

OBJECTIVES
This chapter will:
1. Identify the key indicators of organ dysfunction used to
characterize “critically ill patients.”
2. Discuss key principles of management for critically ill
patients using the VIP rule.
3. Highlight the need for individualized therapy guided by
appropriate monitoring.

4. Describe critical illness as one part of a continuum of
healthcare.

We often hear the term “critically ill,” but exactly how can
we define the critically ill patient? What characteristics
make a patient “critically ill”? Synonyms of the word
critically include dangerously, severely, gravely, profoundly,
and desperately. Although these all stress the serious nature
of this condition, they do not really help define it. In fact,
the key feature that makes a patient critically ill is essentially
the presence (or imminent risk) of acute organ dysfunction.
Importantly, although many critically ill patients have a
“life-threatening” condition, this term, although widely
used in the context of critical illness, is not an essential
component of its definition. For example, patients at risk
of developing acute renal failure may be critically ill, but
they do not necessarily have a life-threatening condition
because, with appropriate support, it is possible to survive
with no renal function.
The critically ill patient may have a single or multiple
disease processes, and the state of critical illness is therefore
difficult to define. For example, some complex patients
with mild acute respiratory distress syndrome (ARDS)
associated with septic shock resulting from peritonitis also
have secondary renal failure and several comorbidities,
e.g., complicated diabetes and chronic obstructive pulmonary
disease (COPD). Critically ill patients therefore are characterized usually by the types and severities of their organ
dysfunction(s), which are different in each patient and
influence treatments and outcomes. In the following section
we will consider the key indicators of organ dysfunction

used to characterize critically ill patients before briefly
discussing some of the general aspects of management and

monitoring that are typically used in these patients and
thus form part of their “critical illness” identity.

ORGAN DYSFUNCTION
Cardiovascular
A patient with cardiovascular dysfunction has insufficient oxygen available to meet tissue requirements, thus
leading to dysfunction of other organ systems. Circulatory
failure or shock can be classified according to the four key
pathophysiologic mechanisms: hypovolemic, cardiogenic,
obstructive, or distributive.1 Shock is recognized clinically
by the presence of hypotension (although this is sometimes
subtle, especially in patients with a history of hypertension)
and typically requires vasopressor therapy. Importantly,
however, shock is not just hypotension, and the tissue
perfusion must be evaluated. This can be accomplished
by using the three “windows” to look inside the body:
skin perfusion, urine output, and mental status (typically
obtundation, disorientation, confusion). An increase in
blood lactate concentration above 2 mEq/L (or mmol/L)
provides important confirmation of abnormal cellular oxygen
metabolism.
Arrhythmias are no longer considered such an important
sign of cardiovascular dysfunction in the critically ill patient,
because the excessive treatment of arrhythmias in the past
was accompanied by more complications than benefits.
Tachycardia does remain an important sign, but patients
should be evaluated carefully using an algorithm to determine the underlying cause. Tachycardia is usually present

to compensate for a low stroke volume (in the presence of
hypovolemia, cardiac pump issues, or an obstruction in
the cardiovascular system) or to generate a supranormal
cardiac output (in sepsis or other inflammatory conditions
or in anemia or hypoxemia).

Respiratory
There are two types of respiratory failure: hypercapnic
(typically related to chronic lung disease or central hypoventilation) and hypoxemic (e.g., in pneumonia or ARDS). In
1


2  Section 1 / Principles of Critical Care
the absence of acute circulatory failure (i.e., when skin
perfusion is adequate), oxygen saturation, measured by
pulse oximetry (SpO2), reflects arterial oxygen saturation
(SaO2) and, therefore, arterial partial pressure of oxygen
(PaO2). However, it cannot differentiate the two types of
respiratory failure. Even on room air, both conditions result
in a low PaO2 and thus in a decrease in SpO2. Arterial
blood gas analysis therefore will be necessary. To avoid an
arterial puncture, venous blood gas analysis can be performed, preferably from a central vein, to estimate PaCO2
(which is a few mm Hg less than the PvCO2).

Renal
Although sensitive markers of renal (dys)function have been
developed (including neutrophil gelatinase-associated
lipocalin [NGAL], kidney injury molecule-1, interleukin
[IL]-18, and cystatin C), serum creatinine concentrations
are still the most widely used indicator of renal function.

Creatinine clearance often is not calculated in acute, rapidly
evolving conditions. Obviously, oliguria is an important
sign of possible renal failure in patients with acute circulatory failure, because urine output may decrease before the
serum creatinine has time to increase.

Hematologic
Anemia is so common in critically ill patients that it is not
even considered as hematologic dysfunction. Rather, the
presence of coagulopathy is considered as the main indication of hematologic function. Because the prothrombin time
can be altered in the presence of liver dysfunction and
during anticoagulant therapy, platelet count is the most
widely used marker of hematologic dysfunction.

Neurologic
There is no better simple test of neurologic function
than the Glasgow coma scale (GCS) score. Obviously, the

estimation of the score can be altered by the administration of sedatives, but sedatives are much less widely used
than in the past. If a patient is sedated or anesthetized,
the “assumed” GCS should be considered, i.e., the score
that the patient would have had in the absence of these
medications.

Hepatic
An increase in liver enzymes is not very specific for liver
damage, because they also can be released by muscle.
Therefore, despite its many limitations, serum bilirubin
concentration is still used as the primary test of liver
dysfunction. Hemolytic anemia is relatively rare but, if
present, obviously should be considered in the interpretation

of bilirubin levels. An increase in bilirubin levels occurs
only late in the development of multiple organ failure but
is sometimes a good indicator of an undrained focus of
sepsis.

Gastrointestinal
Gastrointestinal dysfunction is unfortunately too difficult
to assess objectively. Tolerance to feeding is difficult to
quantify, as are diarrhea and abdominal bloating. Intraabdominal hypertension is an important, but uncommon,
problem.

Quantifying Organ Dysfunction
Given the limitations of assessing gastrointestinal function,
the first six organ systems discussed above (cardiovascular,
respiratory, renal, hematologic, neurologic, hepatic) are
usually the systems that are taken into consideration when
characterizing organ dysfunction in critically ill patients.
Dysfunction of each of these systems can be quantified
using a SOFA score (Table 1.1).2 Fig. 1.1 presents a chart
of the likely pattern of organ dysfunction shown by the
patient described at the beginning of the chapter.

TABLE 1.1 
The Sequential Organ Failure Assessment (SOFA) Score2
SCORE

0

1

2

3

Respiration
PaO2/FiO2, mm Hg

>400

≤400

≤300

≤200
≤100
With respiratory support

>150

≤150

≤100

≤50

≤20

<1.2 (<20)

1.2–1.9

(20–32)

2.0–5.9 (33–101)

6.0–11.9 (102–204)

>12.0 (>204)

No hypotension

MAP <
70 mmHg

Dopamine ≤ 5 or
dobutamine (any
dose)*

Dopamine > 5 or
epinephrine ≤ 0.1
or norepinephrine
≤ 0.1*

Dopamine > 15 or
epinephrine > 0.1
or norepinephrine
> 0.1*

15

13–14

10–12

6–9

<6

<1.2 (<110)

1.2–1.9
(110– 170)

2.0–3.4 (171–299)

3.5–4.9 (300–440)
<500 mL/d

>5.0 (>440)
<200 mL/d

Coagulation
Platelets × 103/mm3
Liver
Bilirubin, mg/dL
(Μmol/L)
Cardiovascular
Hypotension

Central Nervous System
Glasgow coma score

Renal
Creatinine, mg/dL (Μmol/L)
OR urine output

*Adrenergic agents administered for at least 1 hour (doses given are in mcg/kg/min).

4


Chapter 1 / The Critically Ill Patient  3
Type of dysfunction

Main variables

Degree of alteration
Normal

FIGURE 1.1  Possible pattern of organ dysfunction shown
by a patient with mild acute respiratory distress
syndrome associated with septic shock resulting from
peritonitis, secondary renal failure, and comorbid
diabetes and chronic obstructive pulmonary disease.

Circulatory

Blood pressure, lactate,
need for vasoactive agents

Respiratory

SpO2, need for oxygen,
abnormal blood gases

Renal

Creatinine, new biomarkers,
urine output

Hematologic

Platelets,
PT, APTT

Neurologic

Mental status,
Glasgow coma score

Hepatic

Bilirubin

PRINCIPLES OF MANAGEMENT:
THE VIP RULE
The basic resuscitation guidelines for critically ill patients
are based on the VIP (ventilation, infusion, pump) rule
proposed by Max H. Weil many years ago3 (Fig. 1.2). Oxygen
therapy should be given almost systematically to all patients,
although hyperoxia should be avoided. If a pulse oximetry
signal can be reliably obtained (in the absence of altered

cutaneous perfusion), the SpO2 should be maintained at
around 94% to 97%. In the case of severe decompensation,
mechanical ventilation is needed. Noninvasive ventilation
may be tried first and is more effective in hypercapnic than
in hypoxemic respiratory failure. The indications for
endotracheal intubation are not very strict, and clinical
experience plays an important role in deciding when this
should be performed. During mechanical ventilation, low
tidal volumes always should be used. In the presence of
severe hypoxemia, extracorporeal membrane oxygenation
(ECMO) may be required.
Fluid infusion is the basis for an increase in oxygen
delivery obtained by an increase in cardiac output through
the Frank-Starling relationship. When the likely response
to fluids cannot be predicted, the basic clinical approach
is to perform a fluid challenge, i.e., to give a small amount
of fluid over a limited period of time while carefully
monitoring the patient’s response.4 If there is no evident
clinical benefit, the fluid infusion should be stopped without
delay. Signs of fluid responsiveness, such as pulse pressure
variation or stroke volume variation, can sometimes help
to predict the response to fluids, but these are only reliable
in patients who are appropriately monitored and mechanically ventilated. These patients also need to be sedated (to
avoid any triggering of the respirator), and sedation is used
less frequently in the modern intensive care unit (ICU).
The set of circumstances necessary for correct application
of these tests is therefore infrequently met. Passive leg raising
also can be used for this purpose but is not as simple as it
may appear; it requires beat-by-beat monitoring of cardiac
output to identify the transient hemodynamic changes

(monitoring changes in arterial pressure is insufficient.)
The third aspect, “pump,” refers to the use of vasoactive
agents. Norepinephrine is now the vasopressor agent of
choice. The place of vasopressin derivatives has not yet
been defined; although they may perhaps limit edema
formation,5 clinical benefit has not been demonstrated.
Dobutamine can be added in the presence of myocardial

Dysfunction

Failure

The VIP rule

Ventilate
Infuse
Pump

Oxygen administration
Mechanical ventilation?
IV fluids
Blood transfusions?
Vasopressor agents?
Dobutamine?

FIGURE 1.2  The VIP (ventilation, infusion, pump) rule proposed by
Max H. Weil and colleagues.3 IV, Intravenous.

Salvage

Optimization

Stabilization

De-escalation

Live-saving
measures

Provide
optimal
DO2

Provide
organ support
Ensure stability

Wean from
vasoactive agents
Obtain a negative
fluid balance

Time
FIGURE 1.3  The four phases in resuscitation management over time.
DO2, Oxygen delivery. Modified from Vincent and De Backer1.

dysfunction, limiting the need to correct perfusion deficits
with fluids alone.
Importantly, vasopressors should not be withheld until
sufficient fluids have been given, as it is important to

prevent, or at least to limit the duration of, any episode of
arterial hypotension. Even if there is a response to fluids,
this does not necessarily prevent administration of small
doses of norepinephrine when the fluid balance becomes
too positive, because edema is associated with poorer
outcomes.
Therefore the three VIP elements should be administered
together rather than one after the other. As the patient’s
condition improves, the different components can be reduced
as necessary to maintain hemodynamic stability. Indeed,
the time factor is essential because patient requirements
vary over time during the disease process. Four phases are
identifiable in the management of the critically ill patient:
salvage, optimization, stabilization, and de-escalation
(SOSD)1 (Fig. 1.3). In the salvage phase, the aim is emergency