Vittorio E. Andreucci, Series Editor

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1 RENAL STONE DISEASE

2 TOPICS IN RENAL MEDICINE Vittorio E. Andreucci, Series Editor 1. V.E. Andreucci, The Kidney in Pregnancy. ISBN A.R. Clarkson, IgA Nephropathy. ISBN V. Cambi, Short Dialysis. ISBN R. N. Fine, Chronic Ambulatory Peritoneal Dialysis (CAPD) and Chronic Cycling Peritoneal Dialysis (CCPD) in Children. ISBN

3 RENAL STONE DISEASE PATHOGENESIS, PREVENTION, AND TREATMENT edited by CHARLES Y.c. PAK The University of Texas Health Science Center at Dallas ~. " MARTINUS NIJHOFF PUBLISHING A MEMBER OF THE KLUWER ACADEMIC PUBLISHERS GROUP BOSTON DORDRECHT LANCASTER

4 Distributors for the United States and Canada: Kluwer Academic Publishers, 101 Philip Drive, Assinippi Park, Norwell, MA for the UK and Ireland: Kluwer Academic Publishers, MTP Press Limited, Falcon House, Queen Square, Lancaster LA 1 1 RN, UK for all other countries: Kluwer Academic Publishers Group, Distribution Centre, P. O. Box 322, 3300 AH Dordrecht, The Netherlands Library of Congress Cataloging-in-Publication Data Renal stone disease. (Topics in renal medicine) Bibliography: p. Includes index. 1. Kidneys-Calculi. I. Pak, Charles Y. C. II. Series. [DNLM: 1. Kidney Calculi. W] 356 R3928) RC916.R ' ISBN-13: e-isbn-13: DOl: / Copyright 1987 by Martinus NijhoffPublishing, Boston. Softcover reprint of the hardcover 1 st 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 the prior written permission of the publisher, Martinus NijhoffPublishing, 101 Philip Drive, Assinippi Park, Norwell, MA

5 CONTENTS Contributing Authors Preface and Introduction Vll XI 1. Physiochemistry of urinary stone formation NEIL S. MANDEL AND GRETCHEN S. MANDEL 2. PATHOGENESIS OF HYPERCALCIURIA JOSEPH E. ZERWEKH 3. Pathophysiology of nonhypercalciuric causes of stones NEIL A. BRESLAU AND KHASHAYAR SAKHAEE 4. Nutritional aspects of stone disease LAURIE WAINER, VICKI A. RESNICK, AND MAR.TIN I. RESNICK 5. Radiologic considerations LINDA O. JUDGE 6. Diagnostic considerations GLENN M. PREMINGER AND JEAN A. HARVEY 7. Prevention of recurrent nephrolithiasis CHARLES Y. C. PAK 8. Potassium citrate therapy of nephrolithiasis CHARLES Y. C. PAK AND BEVERLEY V. ADAMS v

6 vi Contents 9. Struvite stones JOHN S. RODMAN 10. Contemporary approaches to removal of renal and ureteral calculi DONALD P. GRIFFITH AND RANDALL B. MEACHAM Index

7 CONTRIBUTING AUTHORS Beverley V. Adams, M.S. General Clinical Research Center Neil A. Breslau, M.D. Associate Professor of Medicine Associate Program Director General Clinical Research Center Donald P. Griffith, M.D. Professor of Urology Scott Department of Urology Baylor College of Medicine The Methodist Hospital and the Litho Center 6560 Fannin, Suite 1019 Houston, TX vii

8 viii Contributing authors Jean A. Harvey, M.D. Assistant Professor of Medicine Linda o. Judge, M.D. Assistant Professor of Radiology Director of Radiology, Aston Center Gretchen S. Mandel, Ph.D. Associate Professor of Medicine Co-Director, National V A Crystal Identification Center Medical College of Wisconsin Veterans Administration Medical Center Milwaukee, WI Neil S. Mandel, Ph.D. Professor of Medicine, Biochemistry, Orthopedic Surgery V A Research Career Scientist Director, National V A Crystal Identification Center Medical College of Wisconsin Veterans Administration Medical Center Milwaukee, WI Randall B. Meacham, M.D. Instructor Scott Department of Urology Baylor College of Medicine One Baylor Plaza Houston, TX Charles y.c. Pak, M.D. Donald Seldin Professor of Clinical Investigation Director, Center in Mineral Metabolism and Clinical Research Glenn M. Preminger, M.D. Assistant Professor of Urology and Medicine

9 ix Martin I. Resnick, M.D. Professor and Chairman, Division of Urology Case Western Reserve University School of Medicine 2065 Adelbert Road Cleveland, 0 H Vicki A. Resnick, M.S. Department of Nutrition Case Western Reserve University School of Medicine 2065 Adelbert Road Cleveland, OH John S. Rodman, M.D. Clinical Assistant Professor of Medicine Cornell University School of Medicine 435 East 57th Street New York, NY Khashayar Sakhaee, M.D. Assistant Professor of Medicine Laurie Wainer, M.S., R.D. Department of Nutrition Case Western Reserve University School of Medicine 2065 Adelbert Road Cleveland, OH Joseph E. Zerwekh, Ph.D. Associate Professor of Medicine and Orthopedic Surgery

10 PREFACE AND INTRODUCTION CHARLES Y.c. PAK Major progress has been made in the pathophysiologic elucidation and management of nephrolithiasis during the past two decades. It is now possible to detect the cause of stone disease in more than 95% of patients, to prevent recurrent formation of stones in the majority of patients, and to remove most existing stones less invasively. The assumption of editorship of this book permits me to indulge in the discussion of this progress from my personal perspective. Three somewhat fortuitous events in my academic career dictated my directing major efforts in stone research. The first event occurred in 1963 when, after having completed medical training, I was faced with two years of military service as a participant of the Berry plan. Choices were limited and disconcerting for someone interested in a research career: a staff physician at a military installation or an indian reservation, or a member of a research team in a state penitentiary. An interesting article by Norman Gershfeld on phospholipid monolayers prompted me to write him seeking a position in his laboratory at the National Institutes of Health (NIH) in Bethesda, MD. Partly because of my rudimentary exposure and publication in surface chemistry, I was offered a position as a staff scientist and a position in the Public Health Service which satisfied the requirements of a military service. The two years I spent with Norman were invaluable in placing me on a firm research foundation. Norman taught me how to plan and organize the whole study scheme before beginning, to anticipate various research findings, and to xi

11 xii Preface and introduction be prepared to explain them. The work assigned concerned an examination of phosphate monolayers with various cations including calcium at the airwater interface [1]. Thus, though unappreciated at the time, Norman gave an important exposure to solution chemistry and physical chemistry which were to play such a crucial role in subsequent stone research. The second event occurred in 1965, when I elected to remain at the NIH to join the Endocrinology Branch of Dr. Fredric C. Bartter. Chance again played its role, since, had it not been for a lost baggage with lecture slides by an airline during a recruitment trip, I probably would have chosen a career in cardiology-hypertension research. After presentation without slides, the position I sought in a cardiology-hypertension center was never offered me. Dr. Bartter taught me that clinical research could be an exact science with hypothesis formulation and testing, and need not simply be "data gathering." He nevertheless made me be aware of opportunistic research, to be alert for unusual clinical phenomena, and to be prepared to pursue them though lacking a clearcut hypothesis. He gave me an exposure to metabolic balance techniques, to pathophysiological and clinical aspects of mineral metabolism, and to patients suffering from recurrent nephrolithiasis. Most importantly, he gave me the freedom and independence to explore new directions. The research project chosen for exploration was an ambitious one, testing the hypothesis that the physico chemistry of bone mineral dictates the state of calcium in the whole organism. This problem was approached by an examination of radiocalcium kinetic analysis in patients with metabolic bone diseases [2] and by tonic interaction with synthetic calcium phosphates and bone mineral in vitro [3]. When this study suggested that brushite (CaHP04 2H20) might be the precursor phase for calcium stones, Dr. Bartter encouraged me to pursue it. The third event influencing my career decision occurred in 1972, when I left the NIH to join the faculty at the Southwestern Medical School at Dallas. I had submitted a research grant application to the NIH entitled "Theoretical and Therapeutic Aspects of Calcification." As the title implied, the application dealt with an exploration of a variety of problems in mineral metabolism, including osteoporosis and calcium nephrolithiasis. The NIH review committee recommended that I concentrate on the pathophysiology of hypercalciuria in nephrolithiasis, believing this problem to be amenable for elucidation and appropriate for my background. In retrospect, this advice proved to be sound. An attempted exploration of pathophysiology of osteoporosis at that particular time would certainly have been far less productive. It is truly remarkable that major events in pathogenesis and management of nephrolithiasis occurred during the past 20 years spanning much of my research career, and that I have been a part or a witness to these advances. In order to place this progress in proper perspective, I shall first describe the state of the art in the mid-1960s. I shall then indicate important advances in chronological order. In order to provide a personal flavor, I shall rely heavily

12 on my work; this practice is not meant to disparage the important contributions of my colleagues and friends in the field. What was the state of the art when I so innocently entered the field in 1966? There was considerable excitement that the "evilness" of urine leading to stone formation might be due to a deficiency of a peptide inhibitor [4], the nature of which has yet to be characterized. Although hypocitraturia had been reported in nephrolithiasis, the full impact of this finding in stone pathogenesis and prevention was not appreciated. No reliable techniques were available to quantitate urinary saturation or the inhibitor activity against the crystallization of stone-forming salts. Hypercalciuria of nephrolithiasis was considered to be of unknown origin, as the term idiopathic hypercalciuria implies. Hyperoxaluria of intestinal origin and the pathogenetic significance of hyperuricosuria in calcium stone formation were not appreciated. A substantial percentage (42.9%) of patients with stones carried a diagnosis of normocalciuric nephrolithiasis [5], attesting to a lack of metabolic-physiologic elucidation. Medical treatment armamentarium was confined; the use of methylene blue was in vogue. Open surgery was often used for removal of stones with attendant extensive morbidity. Diagnostic separation was severely hampered by lack of reliable techniques which are now usually taken for granted in evaluation of nephrolithiasis, such as assays for serum parathyroid hormone, a fast and calcium load test, and measures for urinary oxalate and citrate. Even urinary calcium was sometimes unreliably measured, since atomic absorption spectrophotometry now commonplace in most laboratories had just been introduced commercially. There has been an obvious, drastic improvement since 1966, as shown by the following changes instituted in my own laboratory, reflective of a leading center in stone research Activity-product ratio was introduced for the measurement of urinary saturation with respect to brushite [6]. Later, a similar technique was developed for calcium oxalate. These semiempirical approaches, based on actual dissolution or growth of synthetic salts in whole urine, provided a simpler and perhaps more reliable estimate of urinary saturation than was possible with activity product calculations Urinary cyclic AMP was introduced as a measure of parathyroid function [7]. It replaced the cumbersome calcium infusion test Formation product ratio of brushite was developed to quantitate inhibitor activity against calcium phosphate crystallization in individual urine samples [8]. Later, a similar technique was formulated for calcium oxalate. This technique, together with activity product ratio, provided quantitation of the stone-forming process and an assessment of physicochemical action of drugs available for stone prevention Serum immunoreactive parathyroid hormone assay was established Hypercalciuria of nephrolithiasis was categorized into absorptive, renal, and resorptive forms [9]. xiii

13 xiv Preface and introduction Fasting and oral calcium load test was developed in order to facilitate differentiation of hypercalciurias [10]; this procedure was modelled after the classic studies of Nordin [11] Routine oxalate assays in urine were implemented in evaluation of nephrolithiasis, recognizing hyperoxaluria of intestinal origin [12] Routine analysis of uric acid in urine was instituted, cognizant of the pathogenetic role of hyperuricosuria in calcium stone formation [13] Assay for 1,25-(OHhvitamin D in serum permitted a critical appraisal of the role of vitamin D in the pathogenesis of hypercalciurias [14] Routine urinary analysis of citrate disclosed a wide prevalence of hypocitraturia among patients with nephrolithiasis [15] Dr. Clayman introduced percutaneous nephrostolithotomy to the Dallas urologic community Sodium cellulose phosphate was approved by the U. S. Food and Drug Administration as an orphan drug for the treatment of absorptive hypercalciuria Type I after 15 years of work at NIH and Dallas Extracorporeal shock-wave lithotripsy, developed by Chaussey and colleagues in 1980 [16], was established at a Dallas hospital, thus reducing morbidity associated with stone removal Potassium citrate was approved by the FDA for the prevention of hypocitraturic calcium nephrolithiasis and for uric acid lithiasis, following six years of work at Dallas. The progress outlined here has encompassed improvement or refinement in pathophysiologic elucidation, diagnostic differentiation, prevention of recurrence with medical treatment and in removal of existing stones. The advances in each of these areas will be discussed in succeeding chapters. The authors chosen for this task have personal experience in stone research. While some are relatively new in the field, they nevertheless were chosen so as to provide a fresh perspective. All authors have been my collaborators in past or ongoing research. Some are my colleagues at Dallas. This arrangement has assured presentation of a unified view, reflective to some extent of the approach at Dallas. The depiction of a successful, established program itself would seem to be justifiable. Opposing results will not necessarily be ignored. However, they will be presented in an appropriate context of the consensus view, in order to avoid confusion. Some topics may be discussed in several chapters. This repetition was purposely allowed in order to provide completeness to each chapter. This book is dedicated to my administrative coordinator Faye Britton and secretary Inga Ewing for their devotion and trust, and to my wife Jane, my two daughters Laura and Marjorie, and my son Gregory for their understanding and patience. REFERENCES 1. Pak, C. Y. C. and Gershfeld, N. L The detection and removal of trace calcium from water for charged monolayer studies. J. Colloid. Sci. 19:

14 2. Pak, C. Y. c., Zisman, E., Evens, R., Jowsey, J., Delea, C. and Bartter, F. C Treatment of osteoporosis with calcium infusion. Am. J. Med. 47: Pak, C. Y. C. and Diller, E. C Ionic interaction with bone mineral. V. Effect of Mg2+, citrate 3 -, F-, and sol- on the solubility, dissolution and growth of bone mineral. Calc. Tissue Res. 4: Howard, J. E., Thomas, W. c., Smith, L. H., Barker, L. M. and Wadkins, C. L A urinary peptide with extraordinary inhibitory powers against biological "calcification" (deposition) of hydroxyapatite crystals. Trans. Assoc. Am. Physicians 79: Pak, C. Y. c., East, c., Sanzenbacher, L.J., Delca, C. S. and Bartter, F. C Gastrointestinal calcium absorption in nephrolithiasis. J. Clin. Endocrinoi. Metab. 35: Pak, C. Y. C Physicochemical basis for the formation of renal stones of calcium phosphate origin: calculation of the degree of saturation of urine with respect to brushite. J. Clin. Invest. 48: Murad, F. and Pak, C. Y. C Urinary excretion of adenosine 3', 5' -monophosphate and guanosine 3',5'-monophosphate. N. Engi. J. Med. 286: Pak, C. Y. C. and Ruskin, B Calcification of collagen by urine ill vitro: dependence on the degree of saturation of urine with respect to brushite. J. Clin. Invest. 49: Pak, C. Y. c., Ohata, M., Lawrence, E. D. and Synder, W The hypercalciurias: causes, parathyroid functions and diagnostic criteria. J. Clin. Invest. 54: Pak, C. Y. c., Kaplan, R. A., Bone, H., Townsend, J. and Waters, O A simple test for the diagnosis of absorptive, resorptive and renal hypercalciurias. N. Engi. J. Med. 292: Nordin, B. E. c., Peacock, M. and Wilkinson, R Hypercalciuria and calcium stone disease. Clin. Endocrinoi. Metab. 1: Smith, L. H., Fromm, H. and Hofmann, A. F Acquired hypcroxaluria, nephrolithiasis, and intestinal disease. N. Engi. J. Med. 286: Coe, F. L. and Raisen, L Allopurinol treatment of uric-acid disorders in calcium-stone formers. Lancet i: Pak, C. Y. C Physiological basis for absorptive and renal hypercalciurias. Am. J. Physioi. 237:F415-F Nicar, M.J., SkurIa, c., Sakhaee, K. and Pak, C. Y. C Low urinary citrate excretion in nephrolithiasis. Urology 21 : Chaussy, c., Brendel, W. and Schmiedt, E Extracorporeally induced destruction of kidney stones by shock waves. Lancet ii: xv

15 RENAL STONE DISEASE

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