Informing Clinical Practice in Nephrology: The Role of RCTs

246 Pages·2015·3.9 MB·English

by  Mohsen El Kossi

Mohsen El Kossi
Arif Khwaja
Meguid El Nahas
Editors
Informing Clinical
Practice in Nephrology
The Role of RCTs
123
Informing Clinical Practice in Nephrology

Mohsen El Kossi (cid:129) A rif Khwaja (cid:129) Meguid El Nahas
Editors
Informing Clinical Practice
in Nephrology
The Role of RCTs
Editors
Mohsen El Kossi , MBBCh, MSc, MD, FRCP Meguid El Nahas , MD, PhD, FRCP
Doncaster Royal Infi rmary Sheffi eld Kidney Institute
Doncaster Northern General Hospital
UK Sheffi eld
UK
Arif Khwaja , FRCP, PhD
Sheffi eld Kidney Institute
Northern General Hospital
Sheffi eld
UK
ISBN 978-3-319-10291-7 ISBN 978-3-319-10292-4 (eBook)
DOI 10.1007/978-3-319-10292-4
Library of Congress Control Number: 2014960271
Springer Cham Heidelberg New York Dordrecht London
© Springer International Publishing Switzerland 2015
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is
concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction
on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation,
computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this
legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifi cally
for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work.
Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the
Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions
for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution
under the respective Copyright Law.
T he use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not
imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and
regulations and therefore free for general use.
While the advice and information in this book are believed to be true and accurate at the date of publication, neither
the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may
be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.
Printed on acid-free paper
Springer is part of Springer Science+Business Media (www.springer.com)
Pref ace
N ephrology practice has been informed over the last quarter of a century by a large number of
clinical trials that translated animal experimentation fi ndings into the bedside. These clinical
trials have also informed and shaped the Nephrology Practice Guidelines worldwide.
However, a closer look at many of these clinical trials fi nds them wanting and reveals major
fl aws that make their conclusions challengeable and their subsequent impact of practice mis-
guided. Consequently, our practice and guidelines have been shaped in some instances by
clinical trials that are inconclusive at best and misleading in their conclusions and recommen-
dations at worst.
This has prompted the editors of this monograph along with its publisher to call upon
experts in the various fi elds of nephrology to undertake a thorough and critical appraisal and
evaluation of the published clinical trials that have shaped our practice in recent times in gen-
eral nephrology, dialysis, and transplantation. We have also included a critical appraisal tem-
plate based on standard guidelines including the CONSORT statement to allow for a
comparative evaluation of clinical trials within one area of nephrology and also across its dif-
ferent fi elds: General Nephrology, Dialysis, and Transplantation. Of note, the implementation
of the Critical Appraisal template was left entirely to individual authors’ evaluations.
Parameters Yes No Comment
Validity
Is the Randomization Procedure well described? +1 −1
Double blinded ? +2 −2
Is the sample size calculation described/adequate? +3 −3
Does it have a hard primary e ndpoint ? +1 −1
Is the endpoint surrogate? −2 0
Is the follow-up appropriate? +1 −1
Was there a B ias ? −2 +2
Is the drop out >25 %? −1 +1
Is the analysis I TT ? +3 −3
Utility/Usefulness
Can the fi ndings be generalized? +1 −1
Was the NNT <100? +1 −1
Score …
The critical appraisals of mostly randomized clinical trials (RCT) have revealed the strength
but also the weakness of the published literature upon which we base our current practice.
W e hope that the monograph will alert nephrologists worldwide to the value of published
RCT and provide them with a most valuable reference that assists them in their understanding
and evaluation of key publications in nephrology. This in turn should allow them to better
judge the literature upon which they base their daily clinical practice and avoid misplaced and
unfounded assumptions.
T he quality of the clinical practice and health care we deliver as nephrologists depend to a
large extent on the quality of the RCT and publications we base our knowledge and guidelines
upon.
v

Abbreviations
AKI Acute kidney injury
aAMR Acute antibody-mediated rejection
ABPM Ambulatory blood pressure monitoring
ADPKD Autosomal dominant polycystic kidney disease
ALG Anti-lymphocyte globulin
ATG Anti-thymocyte globulin
ATP III Adult Treatment Panel III
BUN Blood urea nitrogen
CAC Coronary artery calcifi cation
cAMR Chronic antibody-mediated rejection
CAPD Continuous ambulatory peritoneal dialysis
CKD Chronic kidney disease
CKD-MBD Chronic kidney disease-mineral bone disorder
CMV Cytomegalovirus
CNIs Calcineurin inhibitors
CRP C reactive protein
CsA Cyclosporine A
CSWD Corticosteroid withdrawal
CTT Cholesterol treatment trialist
CVD Cardiovascular disease
DM Diabetes mellitus
DOPPS Dialysis Outcomes and Practice Patterns Study
DSA Donor-specifi c alloantibodies
DSM Drug Safety and Monitoring
eGFR Estimated glomerular fi ltration rate
Epo Erythropoietin
ESAs Erythropoiesis stimulating agents
ESRD End stage renal disease
FGF23 Fibroblast growth factor 23
FSGS Focal and segmental glomerulosclerosis
Hb Hemoglobin
HD Hemodialysis
HMG-CO Hydroxymethylglutaryl-CoA
IDPN Intradialytic parenteral nutrition
IFG Impaired fasting glucose
ITT Intention to treat
KDIGO Kidney Disease Improving Global Outcomes
KDOQI Kidney Disease Outcomes Quality Initiative
LDL Low-density lipoprotein
MACE Major adverse cardiovascular events
MAP Mean arterial pressure
MCD Minimal change disease
vii
viii Abbreviations
MI Myocardial infarction
MMF Mycophenolate mofetil
MN Membranous nephropathy
MPGN Membranoproliferative glomerulonephritis
mTOR Mammalian target of rapamycin
ND-CKD Nondialysis-dependent CKD
NNT Number needed to treat
NODAT New onset diabetes after transplant
NYHA New York Heart Association
OL-HDF Online hemodiafi ltration
POC Proof of concept
PP Per protocol
PTLD Post-transplant lymphoproliferative disease
RAAS Renin-angiotensin-aldosterone system
RCT Randomized controlled trial
RRT Renal replacement therapy
SCC Squamous cell carcinoma
SCD Sudden cardiac death
SD Standard deviation
TKV Total kidney volume
UAER Urine albumin excretion rate
VC Vascular calcifi cation
Contents
1 Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Clinical Trials: A Critical Appraisal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Vimarsha G. Swami, Julious Okel, Nikhil Shah, Mark J. Courtney,
and Aminu K. Bello
2 Lupus Nephritis Clinical Trials: A Critical Appraisal . . . . . . . . . . . . . . . . . . . . . . 17
Richard J. Glassock
3 ANCA-Associated Glomerulonephritis Clinical Trials: A Critical Appraisal . . . 33
Khalid Mahdi and Arif Khwaja
4 Acute Kidney Injury (AKI) Clinical Trials: A Critical Appraisal . . . . . . . . . . . . . 47
Yangmin Zeng and Adeera Levin
5 Chronic Kidney Disease (CKD) Clinical Trials: A Critical Appraisal . . . . . . . . . . 71
Meguid El Nahas
6 Anemia in Chronic Kidney Disease Clinical Trials: A Critical Appraisal . . . . . . 93
Mohsen El Kossi
7 Lipids and Chronic Kidney Disease Clinical Trials: A Critical Appraisal . . . . . 103
Mohsen El Kossi
8 Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD)
Clinical Trials: A Critical Appraisal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
Mohsen El Kossi and Arif Khwaja
9 Diabetic Nephropathy Clinical Trials: A Critical Appraisal . . . . . . . . . . . . . . . . 127
Meguid El Nahas and Bo Feldt-Rasmussen
10 Primary Glomerular Disease Clinical Trials: A Critical Appraisal . . . . . . . . . . . 153
Richard J. Glassock
11 Hemodialysis Clinical Trials: A Critical Appraisal . . . . . . . . . . . . . . . . . . . . . . . . 183
Charles Chazot
12 Peritoneal Dialysis Clinical Trials: A Critical Appraisal . . . . . . . . . . . . . . . . . . . 199
Simon J. Davies
13 Renal Transplantation Clinical Trials: A Critical Appraisal . . . . . . . . . . . . . . . . 219
Lionel Rostaing and Richard J. Baker
General Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
ix