Handbook of Renal Biopsy Pathology

Second edition

Handbook of Renal Biopsy

Pathology

Second edition

Alexander J. Howie

Professor of Renal Pathology

University College London

London, United Kingdom

Alexander J. Howie

Professor of Renal Pathology

University College London

London, United Kingdom

Library of Congress Control Number: 2007933402

ISBN: 978-0-387-74604-3 e-ISBN: 978-0-387-74605-0

c 2008 Springer Science+Business Media, LLC

All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC., 233 Spring Street, New York, NY10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden.

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Printed on acid-free paper

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Preface

My aim was to write a short, clear, useful, and interesting guide to the findings in renal biopsy specimens. Particular parts of this aim were to show how a diagnosis can be reached, and what information taken from a specimen is clinically significant and helpful. This guide was designed for pathologists and trainee pathologists who look at the specimens, nephrologists and transplant surgeons and their trainees who take the specimens, medical students who will be the next generation to take and look at the specimens, and anyone else who may have contact with people with renal disorders, such as dialysis and transplant nurses and pharmacists.

There is a major difference from most other texts on renal biopsy pathology, which approach the subject by a consideration of each disease separately. In real life, the disease is not known before the biopsy. This text shows how the diagnosis can be made starting from simple information, the clinical indication for the biopsy, followed by interpretation of changes seen in the specimen.

Other features not found in many texts are practical tips on the differentiation between possible diagnoses, information about eponyms and the origins of words, a guide to pronunciation of names, and a mention of famous people who have had renal disorders.

I am grateful to the nephrologists and renal transplant surgeons who have provided most of the material for this book, and have given me help and advice over the years. I also thank colleagues in pathology and related disciplines. From my time in the University of Birmingham, United Kingdom, I thank Dr D Adu, Mr A D Barnes, Ms L J Buist, Dr P Cockwell, Dr M T Drayson, Dr M A S Ferreira Baptista, Mr J Gregory, Dr S A Hulton, Dr G W Lipkin, Prof. C J Lote, Sir Jonathan Michael, Dr D V Milford, Dr F Raafat, Dr P Ramani, Mr A R Ready, Dr N T Richards, Prof. C O S Savage, Mrs J Sparke, Dr S J W Spencer, Dr C M Taylor, Prof. R H R White, and Mrs M C Williams.

In University College London and the Royal Free Hospital, London, United Kingdom, I thank Mr M Al-Akraa, Dr A Burns, Dr J O Connolly, Dr J M Cross, Prof. J Cunningham, Dr A Davenport, Dr P J Dupont, Mr B S Fernando, Mr O N Fernando, Dr J D Gillmore, Dr M A Harber, Dr K A Hillman, Dr S D Jayasena, Dr G L Jones, Prof. R F Kleta, Dr H J Lachmann, Ms J F Lewin, Ms R H H Lord, Dr M A Mansell, Prof. G H Neild, Dr J K Onwubalili,

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Prof. S H Powis, Ms R F Sim, Dr H A F Stephens, Dr P Sweny, Prof. R J Unwin, Mr P S Veitch, Dr D C Wheeler, and Dr R G Woolfson.

Above all, I thank Prof. D B Brewer, who inspired me to become a renal pathologist, and whose book Renal Biopsy (London: Edward Arnold, 1964 and 1973) is a superb guide to renal disease based on his experience.

The chance to prepare a second edition has allowed me to include material that has appeared since the first edition, especially on segmental sclerosing glomerular disorders, lupus nephritis, human immunodeficiency virus, hypertension, and renal transplantation. For this, I am grateful to Springer, and in particular to Melissa Ramondetta, Executive Editor, Clinical Medicine, and Dianne Wuori, Editorial Assistant.

London, July 2007

A J Howie

Contents

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	1
Aims of the Book . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	1
Introduction to Renal Disease from a Pathologist’s Point of View . . . . .	2
The Value of a Renal Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	3
Summary: Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	3
Further Reading: Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	3
2 General Points About Renal Biopsy Specimens . . . . . . . . . . . . . . . . . . . .	5
Introduction to General Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	5
Common Things Are Common and Diseases Present
in Characteristic Ways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	5
Things to Remember About the General Rules . . . . . . . . . . . . . . . . . . . . .	5
Importance of the Request Form to the Pathologist . . . . . . . . . . . . . . . . .	6
Indications for Renal Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	6
Complications of a Renal Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	9
Summary: General Points About Renal Biopsy Specimens . . . . . . . . . . .	9
3 Technical Handling of Renal Biopsy Specimens . . . . . . . . . . . . . . . . . . . .	11
Types of Renal Biopsy Specimen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	11
Fixation and Processing of Specimens . . . . . . . . . . . . . . . . . . . . . . . . . . . .	11
Arrangements for Electron Microscopy of Specimens . . . . . . . . . . . . . . .	14
Sectioning of Specimens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	15
Staining of Specimens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	16
Immunohistologic Study of Specimens . . . . . . . . . . . . . . . . . . . . . . . . . . .	17
Summary: Technical Handling of Renal Biopsy Specimens . . . . . . . . . .	18
Further Reading: Technical Handling of Renal Biopsy Specimens . . . . .	18
4 How to Look at a Renal Biopsy Specimen: Preliminary Study . . . . . . .	19
Immediate Study of Initial Sections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	19
Actions After Immediate Study of Initial Sections . . . . . . . . . . . . . . . . . .	28
Summary: How to Look at a Renal Biopsy Specimen:
Preliminary Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	29

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5 How to Look at a Renal Biopsy Specimen: Initial Study
of the Kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	. . . 31
Introduction to Initial Study of the Kidney . . . . . . . . . . . . . . . . . . . . .	. . . 31
Initial Study of Tubules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	. . . 31
Assessment of Atrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	. . . 32
A Note on Hypertension and the Kidney . . . . . . . . . . . . . . . . . . . . . . .	. . . 35
Initial Study of Glomeruli: Glomerular Size . . . . . . . . . . . . . . . . . . . .	. . . 38
Initial Study of Glomeruli: Distribution of Glomerular
Abnormalities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	. . 40
Initial Study of Interstitial Tissues . . . . . . . . . . . . . . . . . . . . . . . . . . . .	. . . 44
Initial Study of Blood Vessels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	. . . 45
Summary: How to Look at a Renal Biopsy Specimen:
Initial Study of the Kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	. . 47
Further Reading: How to Look at a Renal Biopsy Specimen:
Initial Study of the Kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	. . 48
6 Indication for Biopsy: Nephrotic Syndrome . . . . . . . . . . . . . . . . . . . .	. . . 49
Introduction to the Nephrotic Syndrome . . . . . . . . . . . . . . . . . . . . . . .	. . . 49
Detection and Measurement of Proteinuria . . . . . . . . . . . . . . . . . . . . .	. . . 50
Value of a Renal Biopsy in the Nephrotic Syndrome . . . . . . . . . . . . .	. . . 50
Approach to the Diagnosis in the Nephrotic
Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	. . 51
Initial Inspection of a Renal Biopsy Specimen in the Nephrotic
Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	. . 52
Do Glomeruli Look Normal? Is the Diagnosis Minimal Change
Nephropathy? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	. . 55
Diagnosis of Minimal Change Nephropathy . . . . . . . . . . . . . . . . . . . .	. . . 55
Differential Diagnosis of Minimal Change Nephropathy . . . . . . . . . .	. . . 56
Are Glomeruli Abnormal? Is There Membranous Nephropathy? . . .	. . . 57
Diagnosis of Membranous Nephropathy . . . . . . . . . . . . . . . . . . . . . . .	. . . 59
Differential Diagnosis of Membranous Nephropathy . . . . . . . . . . . . .	. . . 63
Are Glomeruli Abnormal? Is There a Segmental Sclerosing
Disorder? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	. . 65
Segmental Abnormalities at the Tubular Opening . . . . . . . . . . . . . . .	. . . 67
Segmental Abnormalities Not Only at the Tubular Opening . . . . . . .	. . . 74
Human Immunodeficiency Viral Infection and its Effects
in the Kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	. . 77
Diagnosis of Collapsing Glomerulopathy . . . . . . . . . . . . . . . . . . . . . .	. . . 78
Other Findings in the Kidney in Human Immunodeficiency
Viral Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	. . 80
Is the Pathologist Told that the Person Biopsied Has Diabetes
Mellitus? Is There Evidence of Diabetic Glomerulopathy? . . . . . .	. . 82
Value of Renal Biopsy in Diabetes Mellitus . . . . . . . . . . . . . . . . . . . .	. . . 83
Diagnosis of Diabetic Glomerulopathy . . . . . . . . . . . . . . . . . . . . . . . .	. . . 84
Differential Diagnosis of Diabetic Glomerulopathy . . . . . . . . . . . . . .	. . . 88

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Is the Pathologist Told that the Person Biopsied Has Systemic
Lupus Erythematosus? Is There a Possibility
of Lupus Nephritis? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	90
Value of Renal Biopsy in Systemic Lupus Erythematosus . . . . . . . . . . . .	91
Diagnosis of Lupus Nephritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	92
Classification of Lupus Nephritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	95
International Society of Nephrology/Renal Pathology Society
2003 Classification of Lupus Nephritis . . . . . . . . . . . . . . . . . . . . . . . . .	98
Are Glomeruli Abnormal? Is There Amyloid? . . . . . . . . . . . . . . . . . . . . . .	104
Diagnosis of Amyloid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	104
Principles of Polarising Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	106
Determination of the Type of Amyloid . . . . . . . . . . . . . . . . . . . . . . . . . . .	112
Differential Diagnosis of Amyloid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	116
Have Minimal Change Nephropathy, Membranous Nephropathy,
Segmental Sclerosing Disorders, Diabetic Glomerulopathy,
Lupus Nephritis, Amyloid, and Conditions that Could
be Confused with Them Been Excluded? . . . . . . . . . . . . . . . . . . . . . . .	118
Differentiation Between Acute Postinfective Glomerulonephritis
and Subendothelial Membranoproliferative Glomerulonephritis . . . .	121
Other Findings in the Nephrotic Syndrome . . . . . . . . . . . . . . . . . . . . . . . .	122
Summary: Nephrotic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .	136
Further Reading: Nephrotic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . .	137

7 Indication for Biopsy: Acute Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . 139 Introduction to Acute Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 Causes of Acute Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 Value of a Renal Biopsy in Acute Renal Failure . . . . . . . . . . . . . . . . . . . . 141 Acute Abnormalities in Tubules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142 Approach to the Diagnosis in Acute Renal Failure . . . . . . . . . . . . . . . . . . 145 Is There Necrosis in the Kidney? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145

Is There the Expected Number of Tubules in the Kidney? . . . . . . . . . . . . 147 Are There Clues to the Cause of Acute Tubular Damage? . . . . . . . . . . . . 148 Common Findings in Renal Biopsy Specimens in Acute Renal

Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148

Is There Evidence of Renal Vasculitis? . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 Diagnosis of Vasculitic Glomerulonephritis . . . . . . . . . . . . . . . . . . . . . . . 151 Clinical Conditions with Renal Vasculitis . . . . . . . . . . . . . . . . . . . . . . . . . 158

If There is Renal Vasculitis, Are There Clues to Recognisable Conditions? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164

Conditions That Can be Differentiated from Pauci Immune Vasculitic Glomerulonephritis: 1 Henoch–Schönlein Nephritis . . . . . . . . . . . . . . 165

Conditions That Can be Differentiated from Pauci Immune Vasculitic Glomerulonephritis: 2 Lupus Nephritis . . . . . . . . . . . . . . . . . . . . . . . . 170

Conditions That Can be Differentiated from Pauci Immune Vasculitic Glomerulonephritis: 3 Goodpasture’s Disease . . . . . . . . . . . . . . . . . . . 170

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Conditions That Can be Differentiated from Pauci Immune Vasculitic Glomerulonephritis: 4 Cryoglobulinemic Glomerulonephritis . . . . . . 172

Are Glomeruli Abnormal but There Is No Evidence of Vasculitis? . . . . . 175 Diagnosis of Acute Postinfective Glomerulonephritis . . . . . . . . . . . . . . . 175 Diagnosis of Subendothelial Membranoproliferative

Glomerulonephritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176 Impression of Glomerulonephritis Given by Ischemic Glomeruli . . . . . . 177

Has a Glomerular Disorder Been Excluded in Acute Renal

Failure? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177

Has a Glomerular Disorder Been Excluded? Is There a Clue

in Interstitial Tissues to the Cause of Acute Renal Failure? . . . . . . . . 177 Diagnosis of Acute Interstitial Nephritis . . . . . . . . . . . . . . . . . . . . . . . . . . 178 Causes and Associations of Acute Interstitial Nephritis . . . . . . . . . . . . . . 181

Has a Glomerular Disorder Been Excluded? Is There a Clue

in Tubules to the Cause of Acute Renal Failure? . . . . . . . . . . . . . . . . . 183 Findings in Tubules: Myeloma Kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . 184 Findings in Tubules: Myoglobinuria or Crystals . . . . . . . . . . . . . . . . . . . . 186

Has a Glomerular Disorder Been Excluded? Is There a Clue

in Blood Vessels to the Cause of Acute Renal Failure? . . . . . . . . . . . . 188 Changes in Blood Vessels: Vasculitis or Embolism . . . . . . . . . . . . . . . . . 189 Acute Renal Ischemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190 Diagnosis of Small Vessel Vasculopathy, also Called Thrombotic

Microangiopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 Disorders Associated with Small Vessel Vasculopathy . . . . . . . . . . . . . . 194 Summary: Acute Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 Further Reading: Acute Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201

8 Indication for Biopsy: Chronic Renal Failure . . . . . . . . . . . . . . . . . . . . . . 203 Introduction to Chronic Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 Assessment of Chronic Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 Stages of Chronic Kidney Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 Causes of Chronic Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205 Value of a Renal Biopsy in Chronic Renal Failure . . . . . . . . . . . . . . . . . . 206 Findings in Renal Biopsy Specimens in Chronic Renal Failure . . . . . . . 206 Assessment of Renal Biopsy Specimens in Chronic Renal

Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207 Is There a Glomerular Disorder? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207 Differentiation of Types of Segmental Sclerosing Glomerular

Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 Differential Diagnosis of Overload Changes in Glomeruli . . . . . . . . . . . 214

Is There Evidence of a Glomerular Disorder Other than IgA Nephropathy, Diabetic Glomerulopathy, or a Segmental

Sclerosing Condition? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215

Is There No Evidence of a Glomerular Disorder? . . . . . . . . . . . . . . . . . . 215

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Is There Evidence of Chronic Ischemic Damage? . . . . . . . . . . . . . . . . . . . 217 Is There Evidence of a Disorder of Urinary Drainage? . . . . . . . . . . . . . . 219 Is There Evidence of a Medullary Disorder? . . . . . . . . . . . . . . . . . . . . . . . 220 Is There Evidence of a Cystic Disorder in the Cortex? . . . . . . . . . . . . . . . 223 Is There Evidence of a Tubular Disorder? . . . . . . . . . . . . . . . . . . . . . . . . . 225 Is There Evidence of an Interstitial Nephritis? . . . . . . . . . . . . . . . . . . . . . 229 Summary: Chronic Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231 Further Reading: Chronic Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . 232

9 Indication for Biopsy: Hematuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233 Introduction to Hematuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233 Detection of Hematuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233 Investigation of Hematuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234 Value of a Renal Biopsy in Hematuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234 Common Findings in Hematuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235 Approach to the Study of Renal Biopsy Specimens

in Hematuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235 Initial Assessment of Orthodox Light Microscopic Sections . . . . . . . . . . 236

Assessment of Immunohistologic Sections: Is There IgA Nephropathy? . 237 Diagnosis of IgA Nephropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237 Henoch-Schönlein Nephritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240

If IgA Nephropathy Has Been Excluded, Is There an Abnormality on Electron Microscopy? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244

Diagnosis of Thin Glomerular Basement Membrane Disease . . . . . . . . . 245 Diagnosis of Hereditary Nephropathy of Alport Type . . . . . . . . . . . . . . . 246 Other Findings in Hematuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248 Summary: Hematuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250 Further Reading: Hematuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251

10 Indication for Biopsy: Proteinuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253 Introduction to Proteinuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253 Types of Proteinuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253 Value of a Renal Biopsy in Proteinuria . . . . . . . . . . . . . . . . . . . . . . . . . . . 254 Findings in Proteinuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254 Approach to Study of Renal Biopsy Specimens in Proteinuria . . . . . . . . 255

Is There a Segmental Glomerular Disorder? . . . . . . . . . . . . . . . . . . . . . . . 256 Does the Request Form Give Information About

a Systemic Disorder? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257

Does the Specimen Appear Normal or Nearly Normal on Light Microscopy? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258

The Unsatisfactory Nature of the Terms Mesangial Proliferative Glomerulonephritis and Focal or Segmental Proliferative Glomerulonephritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259

Summary: Proteinuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261 Further Reading: Proteinuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261

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11 Indication for Biopsy: Renal Allograft . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263 Introduction to Renal Allograft Biopsy Specimens . . . . . . . . . . . . . . . . . . 263 Reasons for Biopsy of an Allograft Other than Dysfunction . . . . . . . . . . 264 Value of Biopsy of a Renal Allograft . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267 Technical Handling of Renal Allograft Biopsy Specimens . . . . . . . . . . . 268 Approach to the Diagnosis in Renal Allograft Biopsy Specimens . . . . . 268

Is There Evidence of Acute Rejection? . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269 Antibody-mediated Rejection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269 Conventional Acute Rejection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271 Diagnosis of Acute Cellular Rejection, also Called Acute

Tubulo-interstitial Rejection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272 Diagnosis of Significant Acute Cellular Rejection . . . . . . . . . . . . . . . . . . 274 Diagnosis of Acute Vascular Rejection . . . . . . . . . . . . . . . . . . . . . . . . . . . 277 Summary of Acute Rejection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277

Is There Any Other Acute Abnormality Instead of Acute

Rejection, or in Addition to It? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278

Is There Evidence of Chronic Rejection? . . . . . . . . . . . . . . . . . . . . . . . . . . 282 Differential Diagnosis of Late Damage in a Renal Allograft . . . . . . . . . . 285 Is There a Glomerular Disorder? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289

Is There Evidence of a Neoplastic Disorder, or Any Other

Disorder? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294 Summary: Renal Allografts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295 Further Reading: Renal Allografts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304

12 Other Indications for Biopsy of Kidneys . . . . . . . . . . . . . . . . . . . . . . . . . . 305 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305 Investigation of the Kidney in Systemic Disease . . . . . . . . . . . . . . . . . . . 305 Investigation of Metabolic or Other Familial Disorders,

and Disorders of Tubular Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305 Assessment of Effects of Treatment on the Kidney . . . . . . . . . . . . . . . . . 306 Investigation of a Renal Mass . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306 Chance Finding of a Neoplasm in a Renal Biopsy Specimen . . . . . . . . . 308 Summary: Other Indications for Biopsy of Kidneys . . . . . . . . . . . . . . . . . 309 Further Reading: Other Indications for Biopsy of Kidneys . . . . . . . . . . . 315

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317