Proteinuria

Proteinuria Edited by

M. M. Avram The LOllg Islalld College Hospital

Brooklyn, New York

PLENUM MEDICAL BOOK COMPANY New York and London

Library of Congress Cataloging in Publication Data

Main entry under title:

Proteinuria.

Includes bibliographies and index. 1. Proteinuria. 2. Kidney-Disease-Diagnosis. I. Avram, Morrell M. (Morrell

Michael), 1929- . JDNLM: 1. Proteinuria. WJ 343 P967j RC905.P76 1985 616.6'1 85·9305 ISBN-13: 978-1-4612-9502-0 e-ISBN-13: 978-1-4613-2477-5 DOl: 10.1007/978-1-4613-2477-5

© 1985 Plenum Publishing Corporation

Softcover reprint of the hardcover 1 st edition 1985 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

To Maria, Rella, Marc, Eric, Mathew, and David with admiration

for their relentless will, idealism, and hard work

Contribu tors

A. J. ADLER, M.D., Chief, Home Dialysis, Associate Professor of Medi­cine, V. A. Hospital, Brooklyn, New York

M. M. A VRAM, M.D., Chief, Division of Nephrology, Medical Director, The A vram Center for Kidney Diseases, The Long Island College Hospital, Clinical Professor of Medicine, Department of Medicine, Downstate Medical Center, Medical Director, Brooklyn Kidney Cen­ter and Nephrology Foundation of Brooklyn, Brooklyn, New York

DAVID S. BALDWIN, M.D., Professor of Medicine, Department of Medicine, New York University Medical Center, New York, New York

G. M. BERL YNE, M.D., Professor of Medicine, Department of Medicine, Downstate Medical Center, Chief, Nephrology Section, V.A. Hospi­tal, Brooklyn, New York

JOHN D. BOWER, M.D., Professor of Medicine, Department of Medi­cine, University of Mississippi Medical Center, Director, Artificial Kid­ney Unit, Medical Director, Kidney Care, Inc., Jackson, Mississippi

BARRY M. BRENNER, M.D., Samuel A. Levine Professor of Medicine, Department of Medicine, Harvard Medical School, Director, Renal Di­vision, Brigham & Women's Hospital, Boston, Massachusetts

D. E. BROWN, M.D., Instructor, Department of Medicine, V. A. Hospi­tal, Brooklyn, New York

KHALID M. H. BUTT, M.D., Associate Professor of Surgery, Downstate Medical Center, Brooklyn, New York

vii

viii Contributors

MARIA JOSE F. CAMARGO, Research Associate, Department of Phys­iology, Cornell University Medical College, New York, New York

GA Y CASE, R.N., Home Training Unit, Kidney Care, Inc., University of Mississippi Medical Center, Jackson, Mississippi

JHOONG S. CHEIGH, M.D., Director, Inpatient Services, Assistant Professor of Medicine, Cornell University Medical Center, New York, New York

PAUL D. DOOLAN, M.D., Professor of Medicine, Department of Medi­cine, Yale University Medical Center, Division of Nephrology, St. Mary's Hospital, Waterbury, Connecticut

LANCE D. DWORKIN, M.D., Assistant Professor of Medicine, Depart­ment of Medicine, N.Y.U. Medical Center, New York, New York

PIERRE F. FAUBERT, M.D., Assistant Professor of Medicine, Depart­ment of Medicine, Downstate Medical Center, Attending, Division of Nephrology, Brookdale Hospital and Medical Center, Brooklyn, New York

ELI A. FRIEDMAN, M.D., Professor of Medicine, Department of Medi­cine, Chief, Renal Diseases Division, Downstate Medical Center, Brooklyn, New York

RICHARD J. GLASSOCK, M.D., Professor and Chairman, Department of Medicine, Harbor U.C.L.A. Medical Center, Torrance, California

CYRIL J. GODEC, M.D., Director, Department of Urology, The Long Is­land College Hospital, Brooklyn, New York

JOHN P. HAYSLETT, M.D., Professor of Medicine, Department of Medi­cine, Chief, Section of Nephrology, Yale University School of Medi­cine, New Haven, Connecticut

JOHN E. KILEY, M.D., Professor in Medicine & Nephrology, The University of Mississippi Medical Center, Jackson, Mississippi

JAMES M. LUCIANO, M.D., Resident, Department of Medicine, Down­state Medical Center, State University of New York, Brooklyn, New York

Contributors ix

THOMAS MAACK, M.D., Professor of Physiology, Cornell University Medical College, New York, New York

JOHN F. MAHER, M.D., Professor of Medicine, Department of Medi­cine, Director, Nephrology Division, Uniformed Services University of the Health Sciences School of Medicine, Bethesda, Maryland

ARAM V. MANOUKIAN, M.D., Senior Medical Student, Department of Medicine, Downstate Medical Center, State University of New York, Brooklyn, New York

ILENE MILLER, M.D., Instructor in Medicine, Department of Medicine, Assistant Attending Physician, Department of Medicine, Cornell University Medical Center, New York, New York

JANET MOURADIAN, M.D., Clinical Professor of Pathology, Cornell University Medical Center, New York, New York

BRYAN D. MYERS, M.D., Associate Professor of Medicine, Department of Medicine, Division of Nephrology, Stanford University School of Medicine, Stanford, California

C. HYUNG PARK, M.D., Research Associate, Department of Physiol­ogy, Cornell University Medical College, New York, New York

JEROME G. PORUSH, M.D., Chief, Division of Nephrology, Brookdale Hospital Medical Center, Professor of Medicine, Department of Medi­cine, Downstate Medical Center, Brooklyn, New York

ROSCOE R. ROBINSON, M.D., Vice Chancellor, Medical Affairs, Van­derbilt University Medical Center, Professor of Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Ten­nessee

J. E. RUBIN, M.D., Chief, Hemodialysis, V. A. Hospital, Brooklyn, New York

GEORGE E. SCHREINER, M.D., Director, Nephrology Division, Profes­sor of Medicine, Department of Medicine, Georgetown University School of Medicine, Washington, D.C.

M. SEIDMAN, M.D., Attending Physician, Department of Medi-

x Contributors

cine, Nephrology Section, V. A. Hospital, Assistant Professor of Medi­cine, Department of Medicine, Downstate Medical Center, Brooklyn, New York

KURT H. STENZEL, M.D., Medical Director, Rogosin Kidney Center, Professor of Medicine, Biochemistry & Surgery, Chief, Division of Nephrology, The New York Hospital-Cornell Medical Center, New York, New York

J. SUTION, M.D., Instructor, Department of Medicine, V. A. Hospital, Brooklyn, New York

JOHN WANG, M.D., Department of Medicine, Cornell University Med­ical Center, New York, New York

Preface

Decoding the significance of proteinuria as an indicator of severity or prognosis in kidney disease is a stimulating challenge to students and practitioners of nephrology. Sir Richard Bright in 1827 associated pro­teinuria with the disease that bears his name. In the subsequent more than a century and a half, however, the meaning of the linkage between proteinuria and renal disease remains elusive.

Proteinuria is discovered on routine urinalysis in about 10 million Americans, most of whom express no symptoms of kidney disease, each year. From the studies of Robinson (updated in these pages), we know that proteinuria, per se, can be present for 20 years without change in re­nal function, as described in orthostatic proteinuria. By contrast, pro­teinuria may be the harbinger of swift kidney destruction, rarely cul­minating in clinical collapse, a syndrome typifying "malignant proteinuria" as detailed herein by Avram.

Although proteinuria is ubiquitous, an orderly management strategy for rational handling of proteinuria of less than nephrotic range is lack­ing. Separation of tubular proteinuria and transient proteinuria of fever is now possible routinely. This book provides a record of the contribu­tions of investigators and clinicians whose work forms the substrate for production of understanding and, ultimately, marching orders for prac­titioners seeking optimized management for their proteinuric patients.

Generations of investigators have attempted to connect specific uri­nary proteins with distinct kidney disorders. This feat was the result of serendipity in the 1950 observation that Bence Jones proteins are pres­ent in most patients with multiple myeloma. Over the ensuing 20 years, it was learned that small amounts of Bence Jones protein may be pres­ent in normal urine and, more importantly, that the careful study of these urinary constituents and their precursors would serve as a Rosetta stone for clarification of modern immunology.

Might we repeat the successes of the multiple myeloma story by readdressing superficially simple questions? What is proteinuria? What

xi

xii Preface

does its presence mean? And how does its presence alter the biology of the patient or the function of the kidney? Despite its high prevalence, we do not know whether proteinuria is injurious to the kidney or is the product of renal damage, nor do we know (with limited exceptions such as the proteinuria of diabetes or uncontrolled hypertension) how to pre­vent or whether and in what way to treat it.

Until the significance to the patient of documenting proteinuria is elucidated, it will continue as an under detected and inadequately stud­ied mark of kidney disease. As our society reappraises health care costs, including billions spent on t~e treatment of renal insufficiency, it is ap­propriate to direct energy and resources in an attempt to prevent renal disease. Toward this goal, the Division of Nephrology's Avram Center for Kidney Diseases of The Long Island College Hospital in Brooklyn as­sembled these manuscripts on "Proteinuria." It is the editor's hope that this volume will convey the excitement and enthusiasm of the authors. It is the wish of all who contributed that the new information developed may benefit the many patients found to have proteinuria.

This book is divided to consider first a description of proteinuria and its relationship to glomerular and tubular functions. Subsequently, the clinical consequences and management of proteinuria are reviewed. A unique variety of renal protein loss termed "malignant proteinuria" is described, along with its management by pharmacological functional desctruction of the kidneys, a desperate therapeutic maneuver for desperately ill patients, which is euphemistically called medical nephrectomy.

In this tome, representing contributions by brilliant researchers from our prestigious national universities from coast to coast, we take a step in the direction of finding needed answers for the millions of Americans who have proteinuria. Converting tens of years of work by my colleagues and me into a synthesis of the state of the art of proteinuria research has been a fulfilling labor of joy.

M. M. Avrarn, M.D.

Acknowledgments

We wish to acknowledge the support of the National Kidney Founda­tion of New York, the Avram Center for Kidney Diseases of The Long Island College Hospital, and The Long Island College Hospital.

Special thanks to Ms. Phyllis LeBeau for invaluable editorial and technical assistance.

xiii

Contents

Part I. Mechanisms of Proteinuria

1. Glomerular Permselectivity ............................... 3 BARRY M. BRENNER, LANCE AND D. DWORKIN

2. In Vivo Evaluation of Glomerular Permselectivity in Normal and Nephrotic Man ..................................... 17

BRYAN D. MYERS

3. Tubular Handling of Proteins: Absorption of Albumin by Isolated Perfused Proximal Convoluted Tubules of the Rabbit .................................................. 37

C. HYUNG PARK, MARIA JOSE F. CAMARGO, AND

THOMAS MAACK

4. Tubular Proteinuria: Clinical Implications .................. 57 JOHN F. MAHER

5. Clinical Significance of Isolated Proteinuria ROSCOE R. ROBINSON

Part II. Clinical Expressions of Proteinuria

67

6. Clinical Spectrum of Lipoid Nephrosis .................... 83 JOHN P. HAYSLEIT

7. Reversible Renal Failure in Minimal-Change Nephrotic Syndrome .............................................. 93

DAVID S. BALDWIN

8. Proteinuria in Diabetic Renal Allograft Recipients .......... 107 JAMES M. LUCIANO, ARAM V. MANOUKIAN, KHALID M. H. BUIT, AND ELI A. FRIEDMAN

xv

xvi Contents

9. Proteinuria following Renal Transplantation ............... 119 KURT H. STENZEL, JHOONG S. CHEIGH, JANET MOURADIAN, JOHN WANG, AND ILENE MILLER

10. Proteinuria as Seen by the Urologist CiRIL J. GODEC

Part III. Pathophysiological Consequences and Management of Proteinuria

127

11. The Pathophysiological Consequences of Heavy Proteinuria 135 RICHARD J. GLASSOCK

12. Clinical Proteinuria ...................................... 153 GEORGE E. SCHREINER

IV. Expectant or Aggressive Management

13. Water Immersion in Nephrotic Syndrome ................. 165 J. SUTTON, D. E. BROWN, A. J. ADLER, J. E. RUBIN, M. SEIDMAN, E. A. FRIEDMAN, AND G. M. BERLYNE

14. Treatment of Idiopathic Membranous Glomerulopathy 175 JEROME G. PORUSH AND PIERRE F. FAUBERT

15. Malignant Proteinuria: A Newly Described Syndrome and Its Management with Medical Nephrectomy ............... 195

M. M. AVRAM

16. Experience with Medical Nephrectomy .................... 209 JOHN E. KILEY, GAY CASE, AND JOHN D. BOWER

17. Medical Nephrectomy for Proteinuria PAUL D. DOOLAN

217

Epilogue ................................................... 221 RICHARD J. GLASSOCK

Index ............................................... 225