Although it has been appreciated for many years that immune processes underlie most types of glomerulonephritis, it is the recent explosion in knowl edge of cellular and molecular immunology that has prompted another book on the subject. The understanding of the mechanisms involved in renal injury requires the integration of information from in vitro cell-culture systems, experimental models of disease, and clinical studies. This volume draws on all of these sources in an attempt to explain current concepts of nephritis. Increased emphasis is placed on autoimmune processes, as opposed to the deposition of circulating immune complexes, although it will be apparent that these may overlap in the area of "in situ" immune complex formation. Of central importance in autoimmunity is the relationship between antigen pre senting cells (including B cells) expressing MHC class II molecules, autoan tigenic peptides, T helper lymphocytes, and various effector cells. The mechanisms by which the immune system may lead to tissue injury are also becoming better understood, and consideration is given to the role of inflam matory cells, the complement proteins, and soluble factors such as cytokines and eicosanoids."

Currently, individuals interested in seeking an in-depth discussion of transplantation immunology must seek individual articles published in several journals, or extrapolate information from various non-transplant immunology textbooks. The purpose of this text is to provide the reader with a single source of information for the basic science of immunobiology of organ transplantation. It is unique that it focuses on immunobiology from the basic research side, with an emphasis on the cellular and molecular levels. The readers will be physicians, scientists, and graduate students interested and engaged in the study of immunology as it relates to allo- and xenotransplantation. This book is designed to be the reference standard for the immunobiology of transplantation.

This conference and monograph were the result of many collective efforts. The whole concept was formulated one early Wednesday morning at our weekly research meeting at Children's Hospital in our division of urology. We have been most fortunate to have a close collaboration with Bob Levin, Ed Macarak, and Pam Howard who have helped steer the course of our division's growing interest in basic science. At our weekly meetings our laboratory fellow will summarize their current work. Other ongoing areas of investigation in our labs and elsewhere are discussed. We have always made an effort to try and understand what other groups are doing who are working in the area of bladder smooth muscle research. It occurred to us that the best way to really know what everyone working in this field was doing would be to sponsor a 2-day meeting where we could all gather to discuss our ongoing work. A major limitation of the annual meeting of the American Urologic Association or the urology section of the American Academy of Pediatrics is that the scientfic sessions are limited as these are meant to be primarily clinical meetings (as they should be). For this reason the idea of a meeting devoted solely to research about the urinary bladder had great appeal. In addition to allowing for longer presentations than the standard 5 to 7 minutes, every effort would be made to encourage a dialogue amongst the presenters and the audience.

Death on Hemodialysis: Preventable or Inevitable? presents the transactions of the Brooklyn meeting, held in April 1993, including an analysis by Scribner and Schreiner and an introduction by Edmund Bourke. Authors include the heads of dialysis registries for Japan, Europe, and the United States, as well as protagonists of dialyser reuse and short dialysis times. Enthusiasts championed the determination of adequacy of dialysis by formulae or by clinical assessment. All chapters are direct and forceful. The reader will be able to judge the data on what are key controversies in planning dialysis protocols and schedules.

Because of many advances in medicine and biotechnology, an increasing number of individuals are surviving into old age, and we are now challenged to apply sophisticated medical knowledge to the care of the elderly citizen. In nephrology, individuals older than 65 are the fastest-growing group of patients requiring dialysis. Similarly, in increasing numbers, elderly persons present themselves with renal complaints to their family doctor, the geriatrician or the nephrologist. In August 1998, with the financial support of the John A. Hartford Foundation, leaders in geriatrics, nephrology and urology met in Jasper, Alberta, for one week to discuss their areas of special knowledge and to learn from each other. Geriatricians learned from nephrologists, nephrologists learned from geriatricians, and both came to see that they had much in common. All participants discovered a common interest, challenge and commitment, namely, to provide the best renal care to a progressively aging population and to teach their fellows the principles of the other collaborating specialties. This book contains all the papers presented at this meeting and also the text of group discussions on Training and Education, Special Clinical Problems in Geriatric Patients, and Recommendations in Basic and Clinical Research. Nephrology and Geriatrics Integrated will prove useful to both nephrologists and geriatricians in their efforts to manage the renal complaints of the elderly, who come to them in increasing numbers.

The 1991 International Yearbook of Nephrology is the third in a sueeessful .eries whieh has, as its principal aim, thc presentation of a eomprehensive list of topfes of the greatest current relevanee to elinieal nephrologists. We believe that, by following the subjeets eovered by the Yearbook in the broad field of nephrology, the praetieing nephrologist and nephrologist-in-training ean stay abreast of a number of rapidly advaneing fields. To improve the quality of the Yearbook, we have appointed an Editorial Board to provfde suggestions for topies and authors. Thus, we have invited 58 outstanding nephrologists from around the world (the list of them is included in this issue of the Yearbook) to identify annually potential topies for the Yearbook. The reply was exeel lent and the contribution quite outstanding. Thus, for the 1992 Yearbook, we reeeived more than 150 suggestions. A number of them will be included in the next issue if they continue to be viewed as eurrent and important. We also invite readers to suggest topies for upeoming issues of the Yearbook. The present issue, the 1991 Yearbook, represents an improvement over previous volumes. We expeet this trend to be maintained in future years. As in previous issues, all ehapters provide a eomplete, aeeurate and up-to-date list of important references. We are grateful to all the authors for their exeellent eontributions and for having fulfilled the deadline in forwarding their manuseript. Our special thanks to Kluwer Aeademie Publishers for the timely publieation of this volume."

This volume is the first of a biannual series entitled Contemporary Nephrology. The series intends to provide the reader with a broad, authoritative review of the important developments that have occurred during the previous two years in the major areas of both basic and clinical nephrology. We have been fortunate to enlist a distinguished group of scientists, teachers, and clinicians to serve as members of the Editorial Board of this series. We are grateful to them for the outstand- ing contributions they have made to this first volume of Contemporary Nephrology. This volume has fifteen chapters. The first four chapters deal with more basic aspects of nephrology: Membrane Transport (Schafer); Renal Physiology (Knox and Spielman); Renal Metabolism (School- werth); and Renal Prostaglandins (Dunn). Chapters 5-10 are more pathophysiologically oriented, and each contains an "appropriate mix" of basic and clinical information. This group of chapters includes Acid-Base Physiology and Pathophysiology (Arruda and Kurtzman); Mineral Metabolism in Health and Disease (Agus, Goldfarb, and Was- serstein); Hypertension and the Renin-Angiotensin-Aldosterone Axis (Williams and Hollenberg); Immunologically Mediated Renal Disease (Glassock); Acute Renal Failure and Toxic Nephropathy (Anderson and Gross); and the Kidney in Systemic Disease (Martinez-Maldonado). The last five chapters, which are more clinically oriented, include Uremia (Friedman and Lundin); Nutrition in Renal Disease (Mitch); Dialysis (Maher); Renal Transplantation (Strom); and, finally, Drugs and the Kidney (Bennett).

The presence of Chronic Kidney Disease (CKD) increases the risk of death from cardiovascular causes and makes the management of heart failure difficult. The coexistence of CKD and heart failure is increasing in prevalence worldwide and requires a unique and subtle approach to patient management. Managing the Kidney in Heart Failure focuses on the therapeutic management of cardio renal patients. Common heart and kidney failure conditions are presented along with treatment scenarios aimed to reduce cardiovascular mortality and preserve kidney function. Co-authored by a Nephrologist and Cardiologist, each chapter of this concise and practical handbook offers a unified perspective to these chronic conditions.

The 6th triennial meeting of the International Study Group for Tryp- tophan Research (ISTRY) was held May 9-12, 1989 in Baltimore, Maryland (USA). From the wide variety of topics and disciplines represented, as documented in this volume, it is clear that tryptophan research and ISTRY are alive and well. ISTRY traces its or1g1ns to at a tryptophan symposium organized in 1971 by H. Schievelbein at Hohenried near Munich (Germany). Up to that time there had been occasional international tryptophan conferences at irregular inter- vals. A number of participants at the Hohenried meeting felt that an inter- national tryptophan organization should be formed to organize regular meet- ings and to foster collaboration and information exchange on tryptophan-re- lated topics. Thanks mainly to the founding work of H. Schievelbein and W. Kochen, an executive committee was elected and ISTRY was born. The inaugural meeting in 1974 was held in Padova (Italy) to honor L. Musajo, one of the foremost pioneers in tryptophan studies. This first ISTRY meeting was suc- cessfully organized by L. Musajo, G. Allegri, A. De Antoni, and C. Costa, and was critical in assuring the viability of the new organization. Subsequent meetings were held in 1977 in Madison, Wisconsin (USA), organized by R.R. Brown, D.P. Rose, and W.E. Knox, honoring C.P. Berg; 1980 in Kyoto (Japan), organized by O. Hayaishi, R. Kido, Y. Ishimura, T. Deguchi, T. Hino, T.

We are pleased to present to our readers the proeeedings of the Seeond Bari Seminars in Nephrology. The topie of theses proeeedings deals with elinieal and experimental aspeets of aeute renal failure. The Bari Seminars in Nephrology were initiated in 1984 and will be held every two years. It is attended by a large number of international elinieal seientists in the diseiplines of nephrology and related fields. The next Bari Seminars in Nephrology will take plaee dur i n g Ap r i 1 2 0 - 2 4 i n 1 988 'a n d t he t he m e 0 f t he ga t her i n g w i 1 1 be Drugs, Systemie Diseases and the Kidney. \\e are indebted for the generous finaneial support of the Centro Nazionale delle Rieherehe, Italy. Alberto Amerio Pasquale Coratelli Vito M. Campese Shaul G. Massry vii CONTENTS I. PATHOPHYSIOLOGY AND STRUCTURAL CHANGES OF ACUTE RENAL FAlLURE Pathogenesis of Acute Renal Failure 3 M. Burnier and R. W. Schrier Structural-Functional Correlates in Acute Renal Failure . . . . . . 15 G. Eknoyan, D. C. Dobyan, and R. E. Bulger Long Term Clinical and Morphological Evaluation of Acute Renal Failure . . . . . . 27 V. Bonomini, A. Vangelista, G. Frasca, S. Stefoni, M. P. Scolari, and G. Feliciangeli The Role of Renal Biopsy in Acute Renal Failure . . . . . . . . . . 35 G. D'Amico, G. Colasanti Catabolism in Acute Renal Failure: Importance of Glucocorticoids and Lysosomal Enzymes . . . . . 41 A. Heidland, R. M. Schaefer, J. Weipert, E."

There has been a growing awareness that nephrotoxicity represents a key factor in human nephropathies, where, irrespective of the causative agent, only a few clinical end-effects are diagnosed. Thus nephropathies are generally classified as acute or chronic renal failure, malignancies or immunological changes. The weaknesses in diagnosing nephropathies arises because of the effective role the kidney plays in maintaining homeostasis, despite the fact that it has been extensively damaged. The frequencies of some type of chemically-induced acute renal failure is well documented, but the causes of chronic renal failure, malignancy, and other nephropathies are far more difficult to associate with a chemical aetiology. Many of the new therapeutic agents have important beneficial effects, but they are found to have marked nephrotoxic effects. Thus there is a growing urgency to increase the stringency of chemical safety evaluation for their potential nephrotoxic effects. This is strongly countered by the increased financial pressure to identify potentially nephrotoxic chemicals earlier in their development and humanitarian considerations to more closely relate animal test to the clinical situation. Part of the challenge may be achieved by the increasing use of in vitro techniques.

Volume 4 of Contemporary Nephrology summarizes major advances in 16 different areas of nephrology during the years 1985 and 1986. Major changes in the composition of the Editorial Board and authorship of the different chapters have occurred in this volume. Six distinguished contributors have retired from the Editorial Board. They include Dr. Zalman A. Agus, Philadelphia; Dr. Robert Anderson, Denver; Dr. Eli Friedman, Brooklyn; Dr. Richard Glassock, Torrance, California; Dr. James Schafer, Birmingham, Alabama; and Dr. Gordon Williams, Bos ton. We are grateful to them for their outstanding contributions to the of this series and for their advice and suggestions as first three volumes members of the Editorial Board. They certainly deserve substantial credit for the success of this series. Seven outstanding academicians have joined the Board. They in clude Dr. Vito M. Campese, Professor of Medicine at the University of Southern California, who contributed the chapter on "Recent Advances in the Role of the Renal Nervous System and Renin in Hypertension"; Dr. William G. Couser, Professor of Medicine and Head of the Division of Nephrology at the University of Washington in Seattle ("Immunologic Aspects of Renal Disease"); Dr. Garabed Eknoyan, Professor of Medicine and Vice Chairman of the Department of Medicine at Baylor College of Medicine ("The Uremic Syndrome"); Dr. H. David Humes, Associate Professor of Medicine and Chief of the Nephrology Section at the Uni versity of Michigan Medical School, Veterans Administration Medical Center ("Acute Renal Failure and Toxic Nephropathy"); Dr."

LOUIS TOBIAN There are many reasons for suspecting that the medulla of the kidney is involved in the pathogenesis of hypertension. Although our present knowledge does not permit the assignment of a precise and exact role for the medulla, there are so many indications of its involvement that this is an appropriate time for the subject to be thoroughly reviewed, as Drs. MandaI and Bohman have done in this volume. The involvement of the renal medulla in hypertension was first strongly indicated by the studies of Eric Muirhead. Studying renoprival hyperten sion, he demonstrated that the injection of extracts of renal medulla could prevent this type of hypertension in the dog, rabbit, and rat. Subsequently, a number of experiments showed that implants of renal medulla could not only prevent renoprival hypertension but also greatly reduce the level of blood pressure in Goldblatt hypertension in the rat and rabbit. It was later noted that the majority of the surviving cells in these medullary implants were interstitial cells. Pitcock and Muirhead were able to culture these interstitial cells, and implants of the cultured cells lowered blood pressure in renoprival hypertension and Goldblatt hypertension, particularly in the rat. We were able to confirm these general observations by employing implants of medulla in "postsalt" hypertension. The medullary implants did indeed bring the blood pressure down."

The effect of calcium antagonists on heart muscle and blood circulation is the reason that they have found widespread clinical application for a number of years. Less well known, in contrast, is the effect this group of substances has on the kidneys, both on kidney cells and the blood flow through the kidneys. This effect was the subject of a workshop we organized in Tiibingen in June 1986. Different groups studied the effects of these substances, especially in animals, on the processing of calcium by the kidney cells and on blood flow. A possible explanation is that the calcium antagonists block the influx of calcium through special cell canals, especially the cells of the distal tubule. It is necessary to test whether there is a blockade or only a reduction in the passage of calcium. Our understanding of the effect of calcium antagonists is in large part based on the results of morphologic, physiologic, and pharmacologic studies of calcium in the kidneys. The particular processes involved in nephrocalcinosis are special objects of study with regard to calcium antagonists. This book presents the results of experimental studies of the effect of calcium antagonists on nephrocalcinosis and acute renal failure after ischemia. In this context, the clinician is particularly interested in the use of calcium antagonists to protect against the kidney in urolithiasis, in acute renal failure and during kidney transplantation. The book is thus of interest to urologists and nephrologists as well as pharmacologists. biochemists, physiologists, and others in research.

Over the last few years, transplantation knowledge and techniques, as well as insights into pharmacology, have improved, thus enabling greater access to transplantation for patients. The pool of organs for transplantation is stable, and therefore insufficient to cope with the growing demand. To adjust demand and resources in the most equitable way, organ procurement and allocation have been organized nationally and often across borders. The national and international organ exchange programs were studied and discussed during the Congress on Organ Allocation, from which this book is derived. This book describes the state of the art in the management of waiting lists and the allocation of organs in transplantation. It includes chapters on the possibilities of expanding the pool of available cadaver organs. It also analyzes the results of transplantation of cadaver organs from older donors and marginal, non-heart beating donors. Transplantation policies based on the offering of organs by living donors are also described, as is the impact of delayed graft function on organ allocation.

Chronic renal disease has received increasing attention and concern since the passage in 1972 of PL 92-603, which provided coverage for end-stage renal disease (ESRD) treatment by the federal government. The human and economic costs of the ESRD program serve to emphasize the need to prevent or to arrest those diseases resulting in chronic renal failure, since none of the available treatments is without complications and/or side effects. The ESRD program, the only federal one that provides coverage for a catastrophic illness for almost the entire population (those qualifying under Social Security), cost almost $2 billion in 1983. The escalating costs of the ESRD program are attributed to the increasing number of patients requiring treatment and have focused concerns of the United States Government, both Congress and the administration, on ESRD. The National Institutes of Health (NIH), especially the Kidney, Urology, and Hematology Division of the National Institutes of Arthritis, Diabetes, and Digestive and Kidney Diseases (NIADDK), supports a sizable research program that bears on chronic renal disease and in association with this has sponsored many conferences and workshops on research on and causes and complications of chronic renal failure. This book is an outgrowth of the issues addressed by participants at a number of NIH conferences held in the 1980s.

Professor David Kerr Royal Victoria Infirmary) Newcastle upon Tyne Do we need another book on renal disease? There are few small books, particularly from this side of the Atlantic, which provide a really sound foundation of renal physiology, biochemistry and immunology. For two decades "The Kidney" by Hugh de Wardener has given a splendid background in renal physiology but I doubt if any author has brought to this subject as wide an experience and knowledge of basic science as Dr Wardle possesses. His researches have ranged over haematology, the role of in travascular coagulation in acute renal failure, the biochemistry of uremic metabolites, the immunology of glomerulonephritis, to hyperlipidemia in the genesis of arterial disease. In all these topics he has mastered the laboratory techniques as well as studying the patients personally. He therefore has a unique opportunity to show how renal disease can be illuminated by an understanding of the pathogenetic mechanism and to point the way to future treatment more logical than the crude and empirical methods we use today. This approach should appeal particularly to the young graduate whose memory of biocht: mistry and physiology is still reasonably fresh."

Organ Shortage: The Solutions is the latest subject in the Continuing Education series, organized by Fondation Marcel Merieux and Universite Claude Bernard in Lyon. The annual subject is chosen to reflect the status of the topical issues of the year, as taught by leading international experts. The contribution of transplantation and clinical immunology to advanced medicine is considerable and promising. The annual volumes in this series keep the reader abreast of these developments. "

It must be considered that there is nothing more difficult to carry out, nor more doubtful of success, nor more dangerous to handle, than to initiate a new order of things. Machiavelli: The Prince (1513) These are the Proceedings of a Conference on Temperature and Environmental Factors and the Testis which took place at New York University School of Medicine, December 8th and 9th, 1989. There is good reason to believe that this was the first of its kind to address, exclusively, the implications of temperature for this highly thermosensitive organ and its precious genetic cargo. The organizers of the Conference hoped to stimulate interest in this area which, paradoxically, has a considerable literature but which has received scant attention and sometimes outright opposition from clinicians expert in male infertility. There have been studies of the relationship of temperature to reproduction starting in the mid-18th Century with observations of the relationship of water temperature to spawning of fish. There is also a vast literature on the deleterious effects of externally applied heat upon spermatogenesis but little study of the possibility that intrinsic heat may be an important etiologic factor in subfertile semen. Today, fertility research has largely ignored this in favor of research in areas which have not produced successes, in terms of live births, comparable to what can be obtained by varicocelectomy (when appropriate) or scrotal hypothermia: viz. 1. Concentration upon the endocrine aspects of testicular function and its relation to spermatogenesis.

The cause of end-stage renal failure in one-third of patients treated by regular haemodialysis or kidney transplantation is some variety of glomerular disease. Less serious glomerular dis orders are more common and often cause inappropriate conster nation to the patients and, sometimes, to their doctors. Similar clinical features can be produced by pathological lesions ranging from the trivial to the life-threatening, and renal biopsy is often necessary to establish the diagnosis. However, its widespread use during the past 20 years has enabled clinicopathological correlations to be made and the natural history of many 'glomerulopathies' to be established, though large areas of uncer tainty remain. In contrast to symptomatic measures, such as the management of uraemia or the nephrottc syndrome, the use of treatment in arresting the progress of the glomerular lesion itself is controver sial and is based on anecdotal evidence rather than controlled trials. Knowledge of the renal pathology will, at least, enable conditions in which immunosuppressive therapy is appropriate to be distinguished from those which are benign or self-limiting. In this book symptomatic management of the clinical syn dromes is detailed, but classification is firmly based on renal histological appearances. The relevance of immunofluorescent microscopy, ultrathin section examination and electron micros copy to our understanding of pathogenesis is described, as well as the uses of these techniques for morphological discrimination."

In 1968 Drs. B. E. C. Nordin and A. Hodgkinson organized the First International Symposium on Urolithiasis Research in Leeds, England. One hundred and five participants from continental Europe, Great Britain, and the United States met to review their work and exchange ideas regarding the formation of urinary calculi. This meeting achieved several important goals. It pulled together a nidus of workers in the many scientific disciplines that relate to urolithiasis. This nidus served as the seed for research growth in a complex, interdisciplinary field. It established a forum for con tinuing communication in urolithiasis research with subsequent sym posia being held every 4 years. The Williamsburg Symposium was the fourth in the Leeds-Madrid Davos series involving 186 participants from throughout the world. A stated emphasis was on clinical research under way in the field. There were no invited speakers and for the first time the 41 papers that were presented orally at the meeting were selected from 184 submitted abstracts. A total of 134 papers were presented in the poster sessions in the afternoons where informal exchange between interested participants and investigators could occur without the restrictions of a plenary session. Virtually all areas of urolithi asis research from the most fundamental physical chemistry to clinical patterns of disease and specific modes of treatment were presented, reviewed and discussed during the meeting.

When Shaul Massry and Herbert Fleisch asked me to write a foreword for this book, I was honored and eagerly looked forward to reading the many chapters. As they came and I skimmed through them, my mind wandered back to the earliest classic contributions in this field in the late 1920s and early 1930s by Albright and his associates, Greenwald and Gross and Adolph, on the homeostatic regulation of inorganic phosphate and the central role of parathyroid hormone (PTH) in this regulation. They clearly showed the exquisite sensitivity of the renal handling of phosphate to varying dietary and parenteral loads and to changes in the level ofPTH. That two outstanding investigators in the field of divalent ion me tabolism should choose to edit a book solely about the renal handling of inorganic phosphate shows how far we have progressed from these early classics to the recent almost exponential increase in the research and publications related to this subject. Despite this increase, I asked myself, is such a large new monograph, consisting of 13 chapters and 30 distin guished authors, warranted? My reading of these chapters and my learning so much from them convinced me that it is, and my pride was heightened in being asked to write the foreword for this book."

Metabolic and electrolyte disorders can pose special challenges to physicians caring for the critically ill patients. Constrained by time and circumstances, clinicians require rapid access to information to help assess and manage these often life-threatening conditions. In this book, a readily useable road map is presented, emphasizing the interactions among problems and suggesting clear lines of action. Keeping the physiopathological mechanisms to the essential, and maintaining an uncluttered format, each chapter provides guidelines to understanding "how did we get here" and "what should we do now," as quickly and safely as possible. Chapters describe clinical presentation and management of the most common renal, electrolyte, acid-base, metabolic and endocrine disorders, complicating the course of critically ill patients.
Contributing authors are all experts in their respective fields, who regularly engage in the day-to-day management of critically ill patients. In a rapidly changing field, the authors have endeavored to maintain an updated approach, emphasizing the most recent evidence on diagnosis and management. Although controversy in the interpretation and management of some problems is inevitable, the editors see it as a desirable way to depict differing interpretations and solutions for each problem. Each chapter ends with a selected list of key references to facilitate in-depth review of each subject.
As with other titles in the Pittsburgh Critical Care Medicine series, this book is intended for frequent use by both "budding experts" as well as by seasoned practitioners in need for of quick and effective reference.

The Fourth International Congress of Peritoneal Dialysis was held in Venice, Italy, June 29 to July 2, 1987. By this time peritoneal dialysis had emerged as a treatment for a substantial fraction of patients with end-stage renal disease and countless numbers of patients with acute renal failure. This treatment is now practiced worldwide and is the life-sustaining treatment for about 40,000 patients with chronic renal failure, representing 15 to 20% of dialysis therapy in about 1000 centers. It is not surprising, therefore, that the number of health professionals engaged in the investigation and the application of the treatment has also grown exponen tially. The First International Symposium on Peritoneal Dialysis, organized by Dr. A. Treviiio-Be cerra in Chapala, Mexico, in 1978, brought together a group of pioneers when continuous ambulatory peritoneal dialysis was in its infancy. In 1981, Dr. G. M. Gahl chaired the Second Symposium, in West Berlin, when the technique and professional interest were growing con siderably. By 1984, when Dr. 1. F. Winchester and I organized the Third Symposium, the pre sented papers exceeded 100 and there were about 1000 attendees. At that time, it was deemed appropriate to form a more organized group and the International Society for Peritoneal Dialy sis was founded. One of the first actions of the Society was to choose from among several applicants Dr."

The kidney, similar to the heart, plays a three-fold role in essential hypertension. First, it participates in the patho genesis of arterial hypertension. Second, it suffers as a target organ of long-standing hypertension, and third, it experiences the effects of antihypertensive therapy. Perhaps most contested at the present time is the involvement of the kidney in the patho genesis of essential hypertension. More than a century ago, William Osler put forward three basic hypotheses about the "genuine contracted kidney. "l 1. "The hypertrophy can be regarded as an effect to overcome a sort of stop-cock action of the vessels when under the influence of an irritating ingredient in the blood greatly contracted and increased the peripheral resistance. " Clearly this hypothesis of an "irritating ingredient" is perhaps the most convincing nowadays, and numerous attempts have been made to identify a specific vasoconstrictive agent in the blood in essential hypertension. 2. "The obliteration of a large number of capillary territories in the kidney materially raised the arterial pressure. An additional factor of dimin ished excretion of water also heightened the pressure within the blood vessel. " Today we know that fluid volume overload in the presence of reduced renal mass seems to be the most likely mechanism accoun ting for renal parenchymal hypertension and, as shown by Guyton's group, for certain forms of experimental hypertension. 3.