Assessment of Urinary Sediment by Electron Microscopy
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Assessment of Urinary Sediment by Electron Microscopy Applications in Renal Disease Assessment of Urinary Sediment by Electron Microscopy Applications in Renal Disease Anil K. Mandai, M.B.B.S., F.A.C.P. Co-Chief of Nephrology and Professor of Medicine Wright State University and Chief of Nephrology Veterans Administration Medical Center Dayton, Ohio Plenum Medical Book Company New York and London Library of Congress Cataloging in Publication Data Mandal, Ani! K. Assessment of urinary sediment by electron microscopy. Includes bibliographies and index. 1. Kidneys-Diseases-Diagnosis. 2. Urine-Examination. 3. Electron microscope, Transmission. I. Mookerjee, Basab K. II. Title. [DNLM: 1. Kidney Diseases-diagnosis. 2. Microscopy, Electron-methods. 3. Urine-analysis. QY 185 M271a) RC904.M325 1987 616.6'107'58 87-14153 TSBN-13: 978-1-4612-9033-9 e-TSBN-13: 978-1-4613-1851-4 DOl: 10.1007/978-1-4613-1851-4 © 1987 Plenum Publishing Corporation Softcover reprint ofthe hardcover lst edition 1987 233 Spring Street, New York, N.Y. 10013 Plenum Medical Book Company is an imprint of Plenum Publishing Corporation All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher This book is dedicated to those friends whose benevolence and compassion have reinforced my perseverance in the pursuit of many ventures, especially Sheldon C. Sommers, M.D., New York, New York Carl M. Kjellstrand, M.D., Stockholm, Sweden Vincent W. Dennis, M.D., Durham, North Carolina J. Charles Jennette, M.D., Chapel Hill, North Carolina William M. Bennett, M.D., Portland, Oregon Richard D. Bell, Ph.D., Chicago, Illinois Robert W. Schrier, M.D., Denver, Colorado John D. Conger, M.D., Denver, Colorado Kim Solez, M.D., Edmonton, Canada James B. Hudson, M.D., Augusta, Georgia Dinko Susic, M.D., Belgrade, Yugoslavia and Krishan K. Malhotra, M.D., New Delhi, India Special thanks to H. Verdain Barnes, M.D., Professor and Chair, Department of Medicine, School of Medicine, Wright State University, and Mr. Alan Harper, Director, Veterans Administration Medical Center, Dayton, Ohio, for their support in my continuing ventures. Foreword Anil K. Mandai, M.D., is one of the trailblazers in the use of the transmission electron microscope in the study of the urinary sediment. In this book, he reviews his extensive efforts to tie his vast clinical expe rience to his elegant basic research with the electron microscope. The pictures are comprehensive, and the clinical correlates are nicely outlined in tables and text. It may astonish some readers that a book for fellows and clinical nephrol ogists has been written on the use of the transmission electron microscope in the study of urine. Some may view this as a sophisticated research instrument. I, however, applaud the effort. So many discoveries and advances in basic science lie unutilized because clinicians are not aware of the tools available or have little instruction in their use. Maybe that is the reason why so many tests have come and gone, have been found useless and dropped, or have simply been abandoned after being judged too complicated-some because they were, others because they were never applied and interpreted properly. The whole field of research seems to be pulling ahead and away from clinical medicine. Therefore, an effort like this one, which rapidly and clearly tries to introduce an advanced research examination technique into clinical medicine, is worthy of admiration and sup port. The cells, fragments of cells, and their end products that are seen in the urine ought to reflect what goes on in the kidney. Depressingly, though, this prediction is not being borne out by analyses of urinary sediment by ordinary light microscopy. In the old days, when disease categorization was simpler, this technique was extensively used, but now it simply has not kept pace with the increasingly sophisticated classifications based on renal biopsy. Electron micro scopy, which takes our observations down to the subcellular level, should be a vii viii FOREWORD more useful tool, and one's first impression upon studying Dr. MandaI's work is that it is. In any case, it is now available for independent investigation and clinical trials. The ultimate extent of its success and clinical utility cannot be known. Time will tell, but one wishes it well. We do need better noninvasive diagnostic methods to diagnose what goes on in the kidney and to follow changes in renal morphology. Carl M. Kjellstrand, M.D. Karolinska Hospital Stockholm. Sweden Preface In my rounds, whether in general internal medicine or in nephrology, I frequently ask team members, "Have you looked at the urinary sediment?" The answer often is "No." It is a curious phenomenon that physicians promptly order and review chest X rays, abdominal films, or even CAT scans of the kidneys but frequently do not examine the urinary sediment. When it comes to urinalysis in the course of a patient work-up, most individuals only glance at the laboratory slip. This practice is of little consequence in a patient without renal disease; however, it could lead to a misdiagnosis in severe renal disease. Indeed, I have successfully treated a patient with rapidly progressive glomerulonephritis who was initially sent for urological evaluation because of a microscopic hematuria. The finding of only a red blood cell cast during careful examination of a urinary sediment in the presence of 3 + proteinuria facilitated the correct diagnosis. Urine examination dates from the fourteenth century; however, scientific examination of the urine began in the early years of the eighteenth century. Lorenzo Bellini (1643-1704) was apparently the first to discover the importance of urine examination. According to Bellini, urine was composed of water, salt, and tasteless earth or tartar.! This observation was followed by a better under standing of the characteristics of urine, such as its specific gravity and urea and glucose content. In 1801, Jarrold described a method of testing for albumin in the urine.! The next epoch-making step in urinalysis was made by Prout, in 1820. He emphasized the scientific basis for the examination of urine and demonstrated its great value in the diagnosis of disease.! In the same era, Richard Bright, from Guy's Hospital in London, established for the first time the relationship between albuminuria and kidney disease. His name has in th~ past been associated ix x PREFACE with kidney diseases, usually various glomerulonephritides, that were often grouped under the name Bright's disease. Although the English microscopist Robert Hooke had examined urinary sediment using a microscope as early as 1665,2 the microscopic study of urinary sediment did not become really popular until the nineteenth century. Yet the practice of microscopic examination of the urine never attained the momentum of such other techniques as ultrasound of the kidneys. This may be attributed to two reasons: (1) The technique requires some skill in the preparation of specimens and the interpretation of the findings, and (2) the limited resolution of the light microscope, whether phase contrast or polarizing, does not clearly delineate the morphology of the sediment components. These hindrances tended to diminish the enthusiasm of the observer and were probably responsible for the decline in the technique's popularity. For the last decade, urinary sediment has been studied by electron micro scopy. Immunofluorescence techniques have been less frequently used in the study of urinary sediment, and therefore there is little information in this area. Among the electron microscopy studies, the scanning technique has been used mostly to investigate the formation and composition of urinary casts. Transmis sion electron microscopy (TEM) has been used mainly to examine amyloid fibrils in urinary sediment. From these limited observations, it has, in the past, been difficult to validate the general usefulness of this technique in urinary sediment studies. This author has used TEM to examine urinary sediments from patients with a variety of renal diseases. The high resolution of TEM permits delineation of the composition of the casts, identifies different cell types (Le., tubule cells versus urinary tract cells), and reveals the severity of changes in the tubule cells and the presence of structures of clinical significance, such as myeloid bodies, fibrin, and amyloid fibrils. The use of TEM for the study of urinary sediment is an important tech nological advancement in the practice of medicine. Thus, TEM of urinary sed iment can be valuable in diagnosing and managing patients with acute renal failure in whom renal biopsy is risky. Furthermore, a TEM laboratory with one experienced technician can handle a large volume of specimens (5-6 a day) at a reasonable cost ($50-$75 a specimen), making this test attractive for clinical purposes as well as for research. Therefore, it seems reasonable to hope that frequent use of TEM in urinary sediment analysis may point up the value of a complete examination of the urinary sediment and improve the position of uri nalysis relative to other diagnostic tests for renal disease. This book emphasizes the feasibility and practicality of TEM in the ex amination of urinary sediment. For the sake of familiarity, and to preserve tradition, the results of light microscopy of urinary sediment are presented, albeit sparsely. Although the value of urinary sediment studies is highlighted, other PREFACE xi tests are described briefly in some chapters to help the reader synthesize the findings that support the final diagnosis of a renal disease. An outline of the management plan is presented at the end of a chapter, as required. It is hoped that this book will be useful to all involved in the care of patients with renal disease.