Table Of ContentH. U. Zollinger M. J. Mihatsch
Renal Pathology in Biopsy
Light, Electron and Immunofluorescent Microscopy
and Clinical Aspects
With the Collaboration of
F. Gudat U. Riede G. Thiel J. Torhorst
Translated by E. Castagnoli
With 949 Figures
Springer-Verlag
Berlin Heidelberg New York 1978
Professor Dr. Hans Ulrich Zollinger
Dr. Michael Jorg Mihatsch
PD Dr. Fred Gudat
PD Dr. Jochen Torhorst
Institut fUr Pathologie der Universitiit Basel
SchOnbeinstraBe 40, CH-4056 Basel/Switzerland
PD Dr. Urs Riede
Pathologisches Institut der Universitiit Freiburg
AlbertstraBe 19, D-7800 Freiburg/Germany
Professor Dr. Gilbert Thiel
Departement fUr Innere Medizin, Universitiit Basel
SpitalstraBe 21, CH-4056 Basel/Switzerland
Dr. Eugene Castagno1i
c/o Hoffmann-La Roche & Co., Pharmaceuticals MM
CH-4002 Basel/Switzerland
ISBN-13: 978-3-642-66733-6 e-ISBN-13: 978-3-642-66731-2
DOl: 10.1007/978-3-642-66731-2
Library of Congress Cataloging in Publication Data. Zollinger, Hans Ulrich, 1912-. Renal pathology in biopsy.
Bibliography: p. Includes index. 1. Kidneys-Biopsy. I. Mihatsch, Michael Jarg, 1943-, joint author. II. Title.
RC904.Z64 616.6'1'0758 77-23922.
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Preface
Vor die Therapie setzten die Gotter die Diagnose.
Otto NiigeJi
Renal biopsy has decisively enriched renal diagnostics. Kidney diseases
may be monitored during their entire course, and new techniques - such
as immunofluorescence and electron microscopy - may be systematically
applied, resulting in novel insights into the morphogenesis, pathogenesis,
and etiology of kidney lesions. These insights, in turn, have served as
new starting points, in the spirit of the quotation above, for the institution
of causal therapy by the clinician.
This work presents our findings based on 20 years of experience in evaluating
renal biopsies. As of the end of 1974, our computer-supported, systematic
clinical, morphologic, and follow-up evaluation of case material consisted
of over 2000 biopsies, including 679 examined by electron microscopy and
400 by immunofluorescence microscopy. The subsequent 500 biopsies (400
studied by electron microscopy and 300 by immunofluorescence) were con
sidered qualitatively only. In order to enhance qualitative findings with
quantitative data, it was necessary to devise new methods for quantifying
electron-microscopic findings. Additionally, we attempted to correlate cyto
logic and immunofluorescent observations to integrate the isolated findings
of electron microscopy into a vital cytologic pattern of reactions. We also
attempted to evaluate the almost overwhelming flood of publications,
especially those appearing within the last 10 years.
The idea for this book was conceived a decade ago. At that time, however,
our own experience in renal biopsy diagnostics seemed insufficient to sup
port such a major undertaking. In the following years, renal biopsy diagnos
tics developed so rapidly that evaluation of case material very quickly
became out of date. Even though progress is still being made, it now
appears, that by and large, the purely descriptive histopathologic evaluation
of renal biopsy for the more important lesions, e.g., glomerulonephritis,
transplants, and familial diseases, has matured. This is reflected by the
increased attention in the literature to the pathogenesis and etiology of
kidney diseases. We believe, therefore, that the time is ripe for the present
work. Our objectives are:
l. To present the current status of knowledge of the bioptically determinable
aspects of kidney diseases. In order to fulfill this goal, we have considered
as many of the findings in the latest literature as possible (about
2000 references) mindful of the difficulties this poses to the reader.
2. To set up a frame of reference for the use of on-going work of renal
pathologists for whom the section on general pathology is chiefly
intended.
3. To enable the nonspecialized pathologist to arrive at a correct diagnosis
and to recognize which cases merit the attention of specialists. The section
VI Preface
on special pathology is included especially for this purpose and accord
ingly, light-microscopic findings have been used as the main basis for
disease classification. We feel that this nosologic approach is justified
since we are convinced that the majority of renal biopsies can be evaluated
appropriately and reliably with light microscopy only. However, both
routine immunofluorescent and electron-microscopic examinations are
indispensable for the specialist.
4. To further the histopathologic interest of clinicians involved in nephrol
ogy and thus to promote the often diagnostically significant role of
renal biopsy.
Our collaborators helped us in the fields of immunology (F. Gudat),
electronmicroscopy of the blood vessels (U. Riede), clinical findings and
basic knowledge of transplantation (G. Thiel) and pathology of tubules
(1. Torhorst).
We would very much appreciate the help of our readers in calling our
attention to omissions and errors which may occur in this book. We thank
you in advance for your courteous cooperation.
Acknowledgements
The present book would not have been possible without the courteous
and friendly support of numerous clinicians in Switzerland, Germany, and
Italy who kindly sent us renal biopsies and case history material for study
and evaluation. Our thanks are due to the following collegues:
Prof. M. Allgower (Basel) Prof. W. Kiinzer (Freiburg)
Prof. R. Amgwerd (St. Gallen) Prof. G.W. Loehr (Freiburg)
Prof. H. Affolter (Basel) Prof. C. Moeller (Hildesheim)
Prof. A. Blumberg (Aarau) Prof. A. L. Meier (Basel)
PD F. Brunner (Basel) Prof. S. Moeschlin (Solothurn)
Prof. A. U. Buff (Zurich) Prof. R. Nicole (Basel)
Dr. A. Colombi (Luzern) Dr. F.W. Reuter (St. Gallen)
Prof. U. Dubach (Basel) Prof. G. Rutishauser (Basel)
Dr. K.D. Ebbinghaus (Ludenscheid) Prof. G. Stalder (Basel)
Dr. A. Edefonti (Mailand) Prof. o. Stamm (St. Gallen)
Dr. F. Egli (Basel) Prof. o. Spuhler (Zurich)
Dr. W. Freislederer (Augsburg) Prof. H. Sarre (Freiburg)
Prof. F.K. Friederiszick (Dortmund) Prof. M. Schwaiger (Freiburg)
Prof. P. Frick (Zurich) Prof. W. Stauffacher (Basel)
Dr. F. Gaboardi (Mailand) Dr. H. Schmitz (Liidenscheid)
Prof. W. Gerock (Freiburg) Prof. W. Siegenthaler (Zurich)
Prof. H. Herzog (Basel) Prof. M. Schmid (Zurich)
Prof. H. Helge (Berlin) Prof. H. Tholen (Basel)
Dr. E. Imbasciati (Mailand) Prof. A. Thelen (Freiburg)
Dr. T. Lennert (Berlin) Prof. B. Truninger (Luzern)
Prof. F. Koller (Basel) Dr. D. Weingard (Freiburg)
Dr. F. Kesselring (Glarus) Dr.T. Wegmann (St. Gallen)
Prof. R. Kluthe (Freiburg) Prof. H. Willenegger (Liestal)
We are further indebted to the directors of the following institutes of pathol
ogy for their appreciated cooperation in providing us with autopsy material
from patients who succumbed sometime after biopsy: Prof. F. Gloor
(St. Gallen), Prof. Ch. Hedinger (Zurich) and Prof. W. Sandritter (Freiburg).
Our thanks are also extended to Prof. M. Bardare (Milan) for making
available to us immunofluorescent data from children biopsied in Milan.
Among my co-workers who merit our special gratitude and with whom
I have worked together for many years are Dr. J. Moppert, who developed
our immunofluorescent department seven years ago, and PD Dr. W. Les
sauer, who managed our electronic data processing program.
VIII Acknowledgement
We wish to express our appreciation to Dr. P. Schmid (Zurich) in charge
of the Department of Medical Statistics of the Bas1e University for his
invaluable advice on statistical problems.
Without the unstinting and engaged work of our technical assistants who,
with much care and love, prepared our electron micrographs - Mrs. B.
Amsler, Miss B. Baumgartner, Mrs. 1. Bremer, Miss C. Nyffeler, Miss
G. Haberkorn, Mrs. S. Bowald, Miss M. Wacker and Miss G. Krey-the
present work would hardly have been possible, and we thank them all.
The same gratitude is due to Miss M. Nebiker and Mr. H. R. Zysset
for their outstanding skill in preparing schematic drawings and photographs.
The above-instanced colleagues and fellow workers are only a pars pro
toto of the many people who have contributed to this book. We do not
wish to omit extending our acknowledgement to all the archivists who
spared no effort in providing us with findings from case histories, some
of which were decades old. Similar appreciation is due to all of the practicing
physicians and hospital physicians in Switzerland, Germany, and Italy who
were considerate enough to provide us with follow-up data on many of
our patients. In this connection, we wish to express our whole-hearted
gratitude to the directors of the registration offices and death registers
in Germany and Switzerland who, by using "detective" methods, were
able to trace many of our patients who, subsequent to our contact with
them, became scattered throughout the world.
Our very special thanks are due to our publisher, Dr. h.c. H. Goetze, and his
coworkers for his and their understanding help and generous cooperation
in assuring publication of the great number of figures presented in this
book.
Last but not least, we wish to express our great appreciation to the Swiss
National Science Foundation (Grant 3.013.73) whose idealized encourage
ment and financial support over the years has, in the final analysis, made
this work possible.
Table of Contents
Part I. Technique and General Pathology
1. Clinical and Procedural Aspects.
Clinical Aspects .
Procedural Aspects . . . . . .
2. Clinician's Role in Renal Biopsy Management and Processing 5
Biopsy Planning . . . . . . . 5
Tissue Processing by Clinicians . 5
3. Renal Biopsy Management and Processing by the Pathologist 8
Light Microscopy Procedures . 8
Electron Microscopy Procedures 12
Immunohistologic Procedures 14
Morphometry Technique 19
Clinically Related Topics . . 19
4. Histology of Normal Kidney Tissue 21
Glomerulus . . . . . . . . 21
Obsolescent Glomeruli . . 28
Glomerular Morphometry. 28
Juxtaglomerular Apparatus 30
Renal Tubules . . . . . . . 33
Blood Vessels . . . . . . . 39
Interstitium: Connective Tissue, Lymph Vessels and Nerves 44
Histological Artifacts . . . . . . . . . . . . 44
5. Introduction to Renal Histopathology 46
Guidelines for Evaluation of Renal Biopsy. 46
Definitions . . . . . . . . . . . . . . 48
Typical Renal Lesions Under Low Power Magnification. 48
6. Histopathology of the Glomerulus Under High Power Magnification 54
Glomerular Size . . . . . . . . . 54
Hypercellularity . . . . . . . . . 54
Changes in Capillary Loop Lumens. 56
Capillary Loop Necrosis. . . . . . 56
Pathological Capillary Loop Contents. 58
Changes of the Capillary Loop Wall . 62
Changes of Other Glomerular Capillary Wall Constituents 77
Changes of the Mesangium . . . . 96
Changes of the Glomerular Capsule. 100
Glomerular Obsolescence . . . . . 107
X Table of Contents
7. Histopathology of the Juxtaglomerular Apparatus (JGA) 116
Limiting Factors Imposed by Biopsy . . 116
Prognostic Value in Renal Hypertension. 116
Increase in .lGA Size . 117
Decrease in .lGA Size. . . . . . . 117
8. Histopathology of the Renal Tubules. 118
Pro blems in Evaluation . . . . . . . . . . 118
Histopathology of Complex Tubular Changes 118
Cytoplasmic Changes of the Tubular Epithelium 125
Nuclear Changes of the Tubular Epithelium 129
EM Pathology of the Renal Tubules 131
Casts . . . . . . . . . . . . . . . 134
9. Histopathology of" the Renal Interstitium 139
Edema . 139
Sclerosis. . . . . . . . 139
Fibrosis. . . . . . . . 139
Inflammatory Infiltrates . 139
Foam Cells 142
Deposits. . . . . . . . 142
10. Histopathology of the Renal Vessels 147
Ultrastructural Elements in Vascular Changes 147
Specific Vascular Lesions 149
Arteriolar Lesions . . . . . . . 152
11. Immunohistopathologic Parameters 155
Definitions . . . . . . . . 155
Diagnostic Significance of IF 155
Quantification of IF Findings 156
IF Deposition Character 157
Significance of Immunoglobulins and Other Proteins in Glomerulopathy 160
Additional Glomerular IF Findings. . . 164
IF Findings in Nonglomerular Structures 166
Cryoglobulins and Kidney. . . . . . . 169
12. General Differential Diagnosis Between Non-Glomerulonephritic
Nephropathies and Glomerulonephritis . . . . . . . . . . . . . . . . 173
Part II. Histopathology of Specific Renal Disease States
13. General Aspects of Glomerulonephritis . . . . . . 177
Nosology ................. . 177
Basic Morphologic Parameters of Glomerulonephritis 178
Special Clinical Courses of Glomerulonephritis 182
General Pathogenesis of Glomerulonephritis 183
Immunocomplex Glomerulonephritis . 184
General Etiology of Glomerulonephritis. . 187
Table of Contents XI
14. The Diffuse Forms of Glomerulonephritis . . . . 188
Diffuse Endotheliomesangial Glomerulonephritis 188
Extracapillary Accentuated Glomerulonephritis. 218
Membranoproliferative Glomerulonephritis . . 231
Intramembranous Glomerulonephritis. . . . . 252
Epimembranous Glomerulonephritis. . . . . . 261
Mixed Form of Epimembranous and Membranoproliferative
Glomerulonephritis. . . . . . . . . . . . . . . . . . 279
15. Focally Accentuated Glomerulonephritis . . . . . . . . . . . . 282
Embolic, Purulent Focal Glomerulitis, and Thrombotic-Induced
Glomerulonephritis. . . . . . . . . . . . . . . . . . . . 282
Embolic Purulent Focal Glomerulitis . . . . . . . . . . 282
Segmental-Focal Glomerulonephritis in Subacute Bacterial
Endocarditis. . . . . . . . . . . . . . . . . . . . . . 283
Segmental-Focal Glomerulonephritis Associated With Generalized
Intravasal Coagulation . . . . . . . . . . . . . . . . . . . . 287
Segmental-Focal Proliferative and Sclerosing Glomerulonephritis, Focal
Global Sclerosing Glomerulonephritis and Overload Glomerulitis . . . 289
Segmental-Focal Proliferative Glomerulonephritis (Proliferative FGN) 289
Segmental-Focal Sclerosing Glomerulonephritis (Sclerosing FGN) 296
Focal-Global Sclerosing Glomerulonephritis 307
Overload Glomerulitis . . . . . . . . . 308
16. Glomerulonephritic Contracted Kidney (Nonclassifiable Glomerulonephritis,
End-Stage Kidney) . . . . . . . . . . . . . . . . . . . . . . . . 311
17. Special Forms of Glomerulonephritis. . . . . . . . . . . . . . . . . 317
Diffuse and Focally Accentuated Glomerulonephritis Associated With
Systemic Disease . . . . . . . . . . . . . . . . . . . 317
Glomerular Disease in Schonlein-Henoch's Purpura 317
Glomerular Disease in Systemic Lupus Erythematosus 326
Renal Changes in Goodpasture's Syndrome. . . . . 337
Renal Changes in Wegener's Syndrome . . . . . . . 342
Glomerulonephritis in Hypersensitivity Angitis (Microform of
Periarteritis Nodosa) . . . . . . . . . . . . . . . . . . 349
IgA Mesangial Glomerulonephritis . . . . . . . . . . . . . . 350
Early Infantile Glomerulonephritic Contracted Kidney (So-Called
Oligonephronia) . . . . . . . . . . . . . . . . . . . . . . 357
18. Glomerular Minimal Change . . . . . . . . . . . . . . . . . . . . 367
19. Glomerulonephrosis and Glomerulosclerosis . . . . . . . . . . . 380
Idiopathic Unspecific Glomerulonephrosis and Glomerulosclerosis 380
Amyloid Nephrosis. . . . 382
Diabetic Glomerulosclerosis . 391
Hepatic Glomerulosclerosis . 400
Glomerulopathy of Pregnancy 401
Kidney in Plasmocytoma . . 404
Glomerulosclerosis in Waldenstrom's Disease 406
