After a decade or longer, approximately one-third of individuals with either type 1 or type 2 diabetes commence a downhill course in which decreasing renal function and failing vision define a Renal-Retinal Syndrome, dominating all aspects of life and presaging early death. Only a generation ago, survival after onset of end-stage renal disease (ESRD) in diabetes was limited because rehabilitation was preempted by blindness, limb amputation, stroke, and heart disease. By 1998, however, team management has improved the outlook, with preserved sight and return to work and home responsibilities, usually for a decade or longer, following kidney transplantation and laser photocoagulation. Recognition of the critical requirement for blood pressure regulation and metabolic control are central themes in management. In this unique book, the accomplishments of ophthalmologists, nephrologists, diabetologists, transplant surgeons, and basic scientists are blended into a strategic approach that may be readily applied by all those caring for diabetic patients. Each of twenty-one presentations suitable for primary care physicians, as well as for subspecialists concerned with macrovascular and microvascular complications of diabetes, is placed in perspective by an introductory editorial analysis. Promising near-term innovative therapies, including insertion of genetically engineered beta cells or polymer-coated islets of Langerhans, interdiction of kinins that promote retinal angiogenesis, and prevention of synthesis of advanced glycosylated endproducts (AGEs), are presented in detail. While comprehensive care of diabetic patients reflects multiple incremental advances that in sum afford major benefit, this text envisions further remarkable changes likely to suppress and possibly entirely prevent the Diabetic Renal-Retinal Syndrome.

Fresh insights into the pathogenic mechanisms by which hyperglycemia induces tissue and organ injurt are the basis for rapidly evolving promising therapies in diabetes. Especially promising as targets for intervention are products of oxidative stress, including kinins and growth factors. Improving results of renal replacement regimes now incorporating pancreatic islet transplants are able to delay and prevent end-organ damage in diabetic individuals. The evolving story of the taming of diabetes is of direct concern to nephrologists, endocrinologists, ophthalmologists, primary care physicians and medical students.

We are pleased to present to our readers the proceedings of the Fourth Bari Seminars in Nephrology. The Topic of these proceedings deals with tubulo- interstitial nephropathies. The Bari Seminars in nephrology are bi-annual meetings attended by a large international audience comprised of clinician-scientists in the various disci- plines of nephrology and related fields. We trust that our readers will find the content of these proceedings reward- ing and interesting. We are indebted for the generous financial support of the Centro Nationale delle Richerche, Italy. Alberto Amerio Pasquale Coratelli Shaul G. Massry TUBULO-INTERSTITIAL NEPHROPATHIES 1 STRUCTURAL, ASPECTS OF THE RENAL INTERSTITIUM W.KRIZ AND K.V. LEMLEY Institute of Anatomy and Cell Biology, University of Heidelberg, D-6900 Heidelberg 1, F.R.G. Childrens Hospital of Los Angeles, Division of Nephrology, Los Angeles, U.S.A. The interstitium of the kidney includes the extravascular inter- tubular spaces of" the renal parenchyma, with their attendant cellular elements and extracellular substances. It is bounded on all sides by tubular and vascular basement membranes. The lymphatics are considered as part of the interstitium.

The contents of this book represent papers which were presented at the Third International Meeting on "Side-Effects of Anti-Inflammatory and Analgesic Drugs" which was held under the auspices of the University of Verona, Institute of Pharmacology in Verona on 8-11 May 1991. This meeting was held in conjunction with the 13th European Workshop on Inflammation and although publications from this part of the meeting are not published here (they appear in Agents and Actions), we were fortunate in having a group of people interested in inflammation from varying backgrounds. The success of the third meeting followed previous meetings held in Cambridge and Verona respectively and continue a tradition which has now become well established. The meeting brought together physicians, scientists and those concerned with the production and use of anti-inflammatory drugs to a very stimulating conference to discuss basic issues affecting all aspects of side-effects of anti-inflammatory and analgesic drugs as well as their detection and treatment. The meeting was held in the Auditorium of Glaxo Italy and we are very grateful to that company for use of their facilities as well as to the University of Verona, Institute of Pharmacology, for valuable secretarial and administrative help. The success of the conference would not have been possible without valuable financial assistance of the companies listed separately (under Acknowledgements) as well as to the organizers of the 13th European Workshop on Inflammation who collaborated with us.

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."

The last twenty years has seen the biggest revolution in the treatment of renal tract stone that has ever been experienced in the history of urolithiasis. The treatment of upper tract renal stone has progressed from the days of a very traumatic and morbid procedure to the relatively innocuous, walk in/walk out therapy of extracorporeal lithotripsy. This progression of events has resulted in a complete reappraisal of management of all types of urinary calculi. From an initial reluctance to treat many stones because of the trauma involved, we have now passed to a situation where smaller and asympto matic stones may be pre-emptively treated before the treatment of serious clinical problems. It is true to say that in Westemized societies the problem of urolithiasis has almost completely been solved by the advent of advanced technology. In this volume, attention is drawn to the fact that there are still persistent difficulties in treating urolithiasis in the less developed and less affluent societies. The differences in epidemiology of urolithiasis in various areas of the world are highlighted, noting a rapid decrease in the incidence of bladder calculi in impover ished areas where affluence increases. Coupled with this progression of affluence however is the well documented increase in the incidence of upper tract renal stones of oxalate nature. This scenario has been almost universal across all coun tries in the last few decades.

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.

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. "

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 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).

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."

Since oxygen is mainly transported by diffusion within tissue, the oxygen pressure field reflects the local balance between oxygen supply and oxygen consumption and characterizes the state of oxygen supply. Despite large physiological varia- tions (e. g. , hypo-and hyperoxia, hypo-and hypertension, change of energy de- mand), this oxygen pressure field can remain remarkably constant, demonstrating that very effective mechanisms must exist that guarantee the adequacy of oxygen supply. Today, it is possible to describe in detail the responsible effector mecha- nisms that produce such a stable state of oxygen supply, but our knowledge of the reactions that sense tissue oxygen supply and trigger the regulatory responses is still incomplete. Since such knowledge is essential for understanding the system of oxygen supply and the way in which it has developed during evolution, even small progress is important. In this book the important O sensor reactions are discussed as they occur in 2 cells, organs, and organ systems. This broad approach gives an excellent picture of the actual state of knowledge in this field. Professor Dr. D. W. Lubbers Contributors Acker, H. Max-Planck-Institut fUr Systemphysiologie, Rheinlanddamm 201, 4600 Dortmund 1, FRG Bassenge, E. Institut fUr Angewandte Physiologie der Universitat Freiburg, Hermann-Herder-Stral3e 7, 7800 Freiburg, FRG Bingmann, D. Poliklinik fUr zahnarztliche Chirurgie, Universitat Mainz, Augustusplatz 2, 6500 Mainz, FRG Bauer, C. Physiologisches Institut, Universitat Zurich, Winterthurerstral3e 190, 8057 Zurich, Switzerland Busse, R. Institut fUr Angewandte Physiologie, Universitat Freiburg, Hermann-Herder-Stral3e 7, 7800 Freiburg, FRG Delpiano, M. A.

It is increasingly recognized that various transporter proteins are expressed throughout the body and determine absorption, tissue distribution, biliary and renal elimination of endogenous compounds and drugs and drug effects. This book will give an overview on the transporter families which are most important for drug therapy. Most chapters will focus on one transporter family highlighting tissue expression, substrates, inhibitors, knock-out mouse models and clinical studies.

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.

A good knowledge of renal physiology is essential to the understanding of many disease states. The purpose of the book is to set out the principles of renal physiology and normal renal function. Now in its 30th year of continuous publication, this new edition offers a logical progression through renal physiology and pathophysiology. In addition, the anatomy, physiology, pharmacology and pathology of the kidney are covered -- making it highly suitable for system based courses. This 5th edition has been extensively revised and features a wealth of new and widely accepted information about kidney function. This includes our understanding of the role of the glycocalyx and structural proteins in glomerular filtration; details of tubular transport, tight junctions and paracellular transport; and an update of the loops of Henle functioning. Principles of Renal Physiology, 5th Edition is a concise and easily readable text ideal for undergraduate medical and medical science students.

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.

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."

This book started out as a "Manual. " The idea was to offer straightforward instruction on how to handle patients in whom renal function is altered by intrinsic as well as systemic or extrarenal disease. While we have attempted to provide simple approaches to most conditions, we have gone beyond that and offer here more detailed description of pathophysiology, diagnosis and therapy. Thus, the "Manual" has become a Handbook. In so doing we hope we have widened the audience for which the book may be useful. As it now stands, we envision that students, house staff, nephrology trainees, nephrologists, primary-care physicians, and nurses of specialized units, interested in kidney-related disturbances and in alterations of the composi tion of the extracellular fluid, will benefit from reading the Handbook. While providing a rational background for the treatments outlined, each author has attempted to narrate the reasons why such therapy is utilized. Frequently, the information is provided in tables and figures to which ready reference can be made. The flow-chart approach has also been utilized to illustrate pathophysiological sequence or steps in therapy. In most instances, the discussion of pathophysiology has been limited to what is widely ac cepted rather than treading into anything controversial, unless the nature of the problem or the nature of our knowledge is ambiguous."

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."

For more than a generation haemodialysis has been the principal method of treating patients with both acute and chronic renal failure. Initially, developments and improvements in the system were highly technical and relevant to only a relatively small number of specialists in nephrology. More recently, as advances in therapy have dem onstrated the value of haemofiltration in the intensive therapy unit and haemoperfusion for certain types of poisoning, the basic principles of haemodialysis have been perceived as important in many areas of clinical practice. In this volume, the potential advantages of bicarbonate haemo dialysis are objectively assessed, the technical and clinical aspects of both haemofiltration and haemoperfusion discussed and the con tinuing problems associated with such extra corporeal circuits analysed. All the chapters have been written by recognized experts in their field. The increasing availability of highly technical facilities for appropriately selected patients should ensure that the information contained in the book is relevant not only to nephrologists but to all practising clinicians. ABOUT THE EDITOR Dr Graeme R. D. Catto is Professor in Medicine and Therapeutics at the University of Aberdeen and Honorary Consultant Phy sician/Nephrologist to the Grampian Health Board. His current inter est in transplant immunology was stimulated as a Harkness Fellow at Harvard Medical School and the Peter Bent Brighton Hospital, Boston, USA. He is a member of many medical societies including the Association of Physicians of Great Britain and Ireland, the Renal Association and the Transplantation Society."

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.

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.

The master tool of logic is the syllogism. If A> Band B> C, then it must follow as the night the day that A > C. If the major and minor premises are true or scientifically correct by current knowledge, the conclusion is true or at least scientifically correct by current knowledge. The demographer of today beams a clear message, which if not true is at least scientifically correct by current knowledge. In the first 80 years of the Twentieth Century, the 'over-65' population of Americans increased eight fold. By century's end it will have increased 12-fold and shortly thereafter will include one in five Americans. While initially a fact of the developed world, the pace of similar graying is accelerating even more rapidly in the Second and Third Worlds. This gray delta constitutes about 35 million living Americans, who may use one-half or more of the health care resources. A would have to be a lot more foolish than B if they failed to recognize that in the coming decade the causation, case-mix, and area of the gray delta demands a change from early, mid-or even later-century medicine. If Homer Smith was right in saying, "We are what we are because we have the kind of kidneys we have" and "The kidneys make the stuff of philosophy", then the who, what, where, when, and why the gray delta will be cared for must focus on the stuff of geriatric nephrology.