Table Of ContentNEPHROTOXICITY IN THE EXPERIMENTAL AND CLINICAL SITUATION
DEVELOPMENTS IN NEPHROLOGY
Cheigh JS, Stenzel KH, Rubin AL: Manual of Clinical Nephrology of the
Rogosin Center. 1981. ISBN 90-247-2397-3
Nolph KD ed: Peritoneal Dialysis. 1981. ISBN 90-247-2477-5
Gruskin AB, Norman ME eds: Pediatric Nephrology. 1981.
ISBN 90-247-2514-3
Schlick 0 ed: Examination of the Kidney Function. 1981.
ISBN 0-89838-565-2
Strauss J ed: Hypertension, Fluid-Electrolytes and Tub ulopathies in
Pediatric Nephrology. ISBN 90-247-2633-6
Strauss Jed: Neonatal Kidney and Fluid-Electrolytes. 1983.
ISBN 0-89838-575-X
Strauss J. ed: Acute Renal Disorders and Renal Emergencies. 1984
ISBN 0-89838-663-2
Didio LJA, Motta PM eds: Basic, Clinical, and Surgical Nephrology.
1985. ISBN 0-89838-698-5
Friedman EA, Peterson CM eds: Diabetic Nephropathy: Strategy for
Therapy. 1985. ISBN 0-89838-735-3
Dzurik R, Lichardus B, Guder Weds: Kidney Metabolism and Function.
1985. ISBN 0-89838-749-3
Strauss J ed: Homeostasis, Nephrotoxicity, and Anomalies in the
Newborn. 1986. ISBN 0-89838-766-3
Oreopoulos DG ed: Geriatric Nephrology. 1986. ISBN 0-89838-781-7
Paganini EP ed: Acute Continuous Renal Replacement Therapy. 1986.
ISBN 0-89838-793-0
Cheigh JS, Stenzel KH, Rubin AL eds: Hypertension in Kidney Disease.
1986. ISBN 0-89838-797-3
Deane N, Wiheman RJ, Benis GA eds: Guide to Reprocessing of
Hemodialysers. 1986. ISBN 0-89838-798-1
Ponticelli C, Minetti L, D'Amico G eds: Antiglobulins, Cryoglobulins and
Glomerulonephritis. 1986. ISBN 0-89838-810-4
Strauss Jed: Persistent Renal-Genitourinary Disorders. 1987
ISBN 089838-845-7
Andreucci VE, Dal Canton A eds: Diuretics: Basic, Pharmacological and
Clinical Aspects. 1987. ISBN 0-89838-885-6
Bach PH, Lock EA eds: Nephrotoxicity in the Experimental and Clinical
Situation. 1987. ISBN 0-89838-977-1 (Part 1); 0-89838-980-1 (Part 2)
Nephrotoxicity in the
experimental and
clinical situation
Part 1
edited by
P. H. BACH
The Robens Institute
University of Surrey
Guildford, Surrey
England
E. A. LOCK
Biochemical Toxicology Section
Imperial Chemical Industries pIc
Alderley Park, Macclesfield, Cheshire
England
1987 MARTINUS NIJHOFF PUBLISHERS ....
a member of the KLUWER ACADEMIC PUBLISHERS GROUP "
DORDRECHT / BOSTON / LANCASTER
Distributors
for the United States and Canada: Kluwer Academic Publishers, 101
Philip Drive, Assinippi Park, Norwell, MA 02061, USA
for the UK and I:re1and: Kluwer Academic Publishers, MTP Press
Limited, Falcon House, Queen Square, Lancaster LA1 1RN, UK
for all other other countries: Kluwer Academic Publishers Group,
Distribution Center, P.O. Box 322, 3300 AH Dordrecht, The
Netherlands
Book information
ISBR-13:978-94-010-8012-5 e-ISBR-13:978-94-009-3367-5
DOl: 10.1007/978-94-009-3367-5
British Library Cataloguing in Publication Data
Nephrotoxicity in the experimental and
clinical situation. --- (Developments in
nephrology) .
1. Kidneys --- Diseases 2. Toxins
I. Bach, P.H. II. Lock, E.A.
III. Series
616.6'1 RC902
Copyright
Copyright 1987 Martinus Nijhoff Publishers
Softcover reprint of the hardcover 1st edition 1987
All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, or transmitted in any
form or by any means, mechanical, photocopying, recording or
otherwise, without prior written permission of the publishers,
Martinus Nijhoff Publishers, P.O. Box 163, 3300 AD Dordrecht,
The Netherlands.
CONTENTS
Preface viii
List of Contributors ix
PART 1
1. Fixation of renal tissue for cytochemical
evaluation
M. A. Williams 1
2. The application of histochemistry at the light
microscopic level to the study of nephrotoxicity
P.H. Bach, N.J. Gregg and E.D. Wachsmuth 19
3. Cryomicrotomy of renal tissue, and the use of X -ray
microanalysis and autoradiography at the light and
electron microscopic levels
J.R.J. Baker 85
4. Fixation of kidney tissue for morphometric study
M.A. Williams and J. I. Lowrie 141
5. Correlating structural and functional changes
in nephrotoxic renal injury
D.C. Dobyan, G. Eknoyan and R.E. Bulger 167
6. Naturally occurring renal disease in non-human
primates
P.N. Skelton-Stroud and J.R. Glaister 189
7. Chemically induced epithelial tumours and
carcinogenesis of the renal parenchyma
G.C. Hard 211
v
NEPHROTOXICITY IN THE EXPERIMENTAL AND CLINICAL SITUATION
8. Assessment of the kidney in relation to blood
pressure regulation
J. Atkinson 251
9. Renal slices and perfusion
w.o. Berndt 301
10. The use of single nephron techniques
in renal toxicity studies
J. Diezi and F. Roch-Ramel 317
11. Prostaglandins and other eicosanoids
K. Crowshaw 359
12. Xenobiotic metabolism in the mammalian kidney
J. B. Tarloff 371
13. Metabolism of glutathione in the kidney
K. Ormstad 405
14. Metabolic activation of halogenated chemicals
and its relevance to nephrotoxicity
E.A. Lock 429
Index xiii
PART 2
15 . Light hydrogen nephropathy and renal carcinoma
M. Lipsky and B. F. Trump 463
16. Metallothionein and its involvement in heavy
metal induced nephropathy
K. Cain 473
17. Detection of nephrotoxicity of foreign chemicals
with the use of in vitro and in vivo techniques
s. Kacew 533
18. Proteins, enzymes and cells in urine as indicators
of the site of renal damage
M.D. Stonard 563
19. The measurement of kidney-derived immunologically
reactive material in urine and plasma for studying
renal integrity
A.B.St. J. Dawnay and W.R. Cattell 593
20. Extrapolation of animal data to man: the concordance
between toxicity screening and clinical consequence
G.A. Porter 613
vi
CONTENTS
21. Antibiotics: the experimental and clinical situation
P. G. Davey and E. S. Harpur 643
22. Mechanisms of metal-induced nephrotoxicity
B . A. Fowler, P. Mistry and P. L. Goering 659
23. Naturally occurring environmental contaminants
W.o. Berndt 683
24. Radiographic contrast media
K. Golman, E. Holtz and T. Almen 701
25. Immunologically mediated nephritis induced
by toxins and drugs
P. Druet, C. Jacquot, D. Baran, D. Kleinknecht,
J.P. Fillastre and J.Ph. Mery 727
26. Clinical and experimental nephrotoxicity of cancer
chemotherapeutic agents
C.L. Litterst and R.B. Weiss 771
27. Radiation-related renal damage
M.E.C. Robbins and J.W. Hopewell 817
28. Epidemiology in the assessment of nephrotoxicity
D.P. Sandler 847
Index xiii
vii
PR.EFACE
There are many aspects of renal function and malfunction that we
still do not understand. Homeostasis is central to renal function,
but its maintenance also serves to mask the earliest features of
malfunction. Thus renal dysfunction is buffered and cannot be
identified until degeneration has reached a level at which homeos-
tasis is severely compromised. Because of this, diagnosis of the
vast majority of nephropathies are often so late as to preclude
therapeutic intervention. More importantly, it has been impossible
to establish the aetiology of many nephropathies.
The kidney is known to be a frequent target for toxicity,
because of its size in relation to the many functions it must per-
form. All to often in the past there has been a failure to
adequately perceive this in the early development of new
therapeutic agents, their clinical trials and subsequent drug
usage. Industrial and environmental chemicals have also been impli-
cated in several nephropathies, but the causal link with exposure
to the offending chemical may not have been immediately estab-
lished.
These volumes cover the different methods that are used to
assess renal function in health and disease. The biology of many
model nephropathies that are directly relevant to the clinical situa-
tion (especially those where a mechanistic understanding is helping
to define the primary lesion and its secondary consequences) and a
broader appreciation of the different types of clinical neph-
rotoxicity and factors that may affect their diagnosis and progres-
sion. The objective of NEPHROTOXICITY IN THE EXPERIMENTAL
AND CLINICAL SITUATION is to use a multidisciplinary scientific
approach as the foundation to better understand nephrotoxicity.
The experimental systems will serve to provide a basis for im-
proved screening for potentially nephrotoxic drugs and chemicals,
the development of less nephrotoxic drugs, they will improve the
approach to the prevention of nephrotoxicity and also provide a ra-
tional basis for the more successful clinical management of all
nephropathies.
Peter H. Bach, Guildford, Surrey
Edward A. Lock, Alderley Edge, Cheshire
viii
LIST OF CONTRIBUTORS
T. Al.JDi!n R.E. Bulger J. Died
Department of Diagnostic Renal Research Laboratory Institut de Pharmacologie
Radiology University of Texas Universite de Lausanne
Malmo General Hospital Graduate School of Bugnon 27
S-214 01 MalmO Biomedical Sciences CH-1005 Lausanne
Sweden PO Box 20708 Switzerland
Houston
J. Atkinson TX 77030 D.C. Dobyan
Laboratoire de USA Renal Research Laboratory
Pharmacologie University of Texas
Faculte des Sciences K. Cain Graduate School of
Pharmaceutiques et MRC Toxicology Unit Biomedical Sciences
Biologiques Woodmansterne Road PO Box 20708
54000 Universite de Carshalton Houston
Nancy 1 Surrey TX 77030
5 rue Albert Ie Brun SM5 4EF USA
Nancy UK
France P. Druet
W.R. Cattell INSERM U. 28
P.R. Bach Department of Nephrology Hopital Broussais
The Robens Institute St Bartholomew's Centre 96 rue Didot
University of Surrey for Research 75674 Paris Cedex 14
Guildford St Bartholomew's Hospital France
Surrey London
GU2 5XH EClA 7BE G. Eknoyan
UK UK Department of Medicine
Baylor College of
J.R.J. Baker K. Crooosbaw Medicine
Department of Biology aNa Pharmaceutical Houston
Research Centre Company Texas 77030
Cilia-Geigy London Office USA
Pharmaceuticals St Alphage House
Wimblehurst Road 18th Floor J.-P. Fillastre
Horsham 2 Fore Street Department of Nephrology
West Sussex London Hopital de Bois-Guillaume
RH12 4AB EC2Y 5DA 2720 route de Neuf-Chatel
UK UK 76230 Bois-Guillaume
France
D. Baran P.G. Davey
INSERM U.28 Department of Clinical B.A. FOIIler
Hopital Broussais Pharmacology National Institute of
96 rue Didot Ninewells Hospital and Environmental Health
75674 Paris Cedex 14 Medical School Sciences
France Dundee PO Box 12233
DD1 9SY Research Triangle Park
w.o. Berndt UK NC 27709
Department of USA
Pharmacology A. Dawnay
University of Nebraska Department of Chemical J .R. Glaister
Medical Center Pathology Hazleton Laboratories
42nd Street and Dewey St Bartholomew's Centre (Europe) Ltd
Avenue for Research Otley Road
Omaha St Bartholomew's Hospital Harrogate
NE 68105 London North Yorkshire
USA EClA 7BE HG3 lPY
UK UK
ix
NEPHROTOXICITY IN THE EXPERIMENTAL AND CLINICAL SITUATION
P.L. GoeriDg J.W. ~ J.-P. JIery
Center for Services of CRC Normal Tissue Department of Nephrology
Radiological Health Radiobiology Research Hopital Bichat
Division of Life Sciences Group 170 Bd. Ney
Food and Drug Research Institute 75018 Paris
Administration (University of Oxford) France
12709 TWinbrook Parkway Churchill Hospital
RockV1lle, MD 20857 Oxford P. IIistry
USA 0X3 7LJ Department of
UK Biochemistry
K.S. Goldstein Brunel University
Department of C. Jacquot Uxbridge, Middx.
Investigative INSERM U.28 UB8 3PH
Toxicology Hopital Broussais UK
Smith Kline & French 96 rue Didot
Laboratories 75674 Paris Cedex 14 K. Omstad
1500 Spring Garden Street France Department of Forensic
PO Box 7929 Medicine
Mail Code L-66 S. lCacar Karolinska Institute
Philadelphia, PA 19101 Department of Box 60400
USA Pharmacology S-10401 Stockholm
University of ottawa Sweden
K. GolDm. 451 Smyth Road
Department of ottawa G.A. Porter
Experimental Research Ontario Department of Medicine
MalmO General Hospital KlH BM5 Canada Oregon Health Sciences
S-214 01 MalmO University
Sweden D. KleiDJmecb.t 3181 S.W. Sam Jackson
Hopital de Montreuil Park Road
M.J. Gregg 56 bd. de la Boissiere L-455
The Robens Institute 93105 Montreuil Cedex Portland
University of Surrey France OR 97201
Guildford USA
Surrey 11.11. Lipsky
002 5XH Department of Pathology II.E.C. RdlIrlDs
UK University of Maryland CRC Normal Tissue
School of Medicine Radiobiology Research
G.C. IIimi 10 South Pine Street Group
Fels Research Institute Baltimore Research Institute
3420 N. Broad Street MD 21201 (University of Oxford)
Temple University School USA Churchill Hospital
of Medicine Oxford
Philadelphia, PA 19140 C.L. Littarst 0X3 7LJ
USA Developmental UK
Therapeutics Program
E. S. IIaJ:pur Division of Cancer F. Rocb.-a-:\.
Department of Treatment Institute de
Pharmaceutical National Cancer Institute Pharmacologie
Sciences Bethesda Universite de Lausanne
Aston University Maryland Bugnon 27
Aston Triangle USA CH-1005
Birmingham Lausanne
B47 ET E.A. Lock Switzerland
UK Biochemical Toxicology
Section D.P. Saodler
E.lIoltz ~rial Chemical Epidemiology Branch
NYCOMED AjS Industries plc Division of Biometry and
Box 4220 Central Toxicology Risk Assessment
0401 Oslo 4 Laboratory National Institute of
Norway Alderley Park Environmental Health
Macclesfield Sciences
J.B. Hook Cheshire PO Box 12233
Preclinical Research and SKID 4TJ Research Triangle Park
Development UK NC 27709
Smith Kline & French USA
Laboratories J.I. Lowrie
1500 Spring Garden Street Department of Anatomy and
PO Box 7929 Cell Biology
Mail Code L7 35 University of Sheffield
Philadelphia Western Bank
PA 19101 Sheffield
USA SID 2TN, UK
x
