The need for adequate means by which to improve urine output is very old. Even in the "Scuola Salernitana", the oldest medieval medical school in Western Europe, about 1000 years ago it was taught how to improve urine output. The list of known "diuretica" included herbs, plants, roots, vegetables, in particular asparagus, fennel and carrot. The first diuretic drugs, however, were mercurial compounds. Thus, calomel, mercurous chloride, was initially used as a diuretic in the sixteenth century by Paracelsus, being one of the ingredients of the so-called "Guy's Hospital pill". But calomel had a cathartic effect so that it was replaced by organic mercurial compounds. These diuretics were clearly toxic. After the discovery of the car bonic anhydrase, in the early 1930s, and the introduction of sulfanilamide as a chemotherapeutic agent, it was observed that this drug was inhibiting carbonic anhydrase in vitro and urinary acidification in vivo thereby causing metabolic acidosis; urine output, however, appeared to increase. Subsequent studies led to the synthesis of more potent analogs, in particular acetazolamide. Studies on car bonic anhydrase inhibitors led to the synthesis of benzothiadiazides which disclosed much less inactivating action on carbonic anhydrase and much more diuretic effect through an inhibition of tubular transport of sodium and chloride. Chlorothiazide was the first member of this class of diuretics. Thiazides are still used in clinical practice.

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 phospholi pid monolayers prompted me to write him seeking a position in his laboratory of Health (NIH) in Bethesda, MD. Partly because of at the National Institutes 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."

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.

Once dialysis treatment, in 1960, permitted life prolongation for some but not all patients in kidney failure, an ethical genie' was released. The introduction of peritoneal dialysis and kidney transplantation compounded the physician's dilemma by underscoring those left untreated. Who should be selected for uremia therapy? Should exclusion from treatment be properly delegated to administrators or physicians, or better left to a committee? Are some candidates more worthy than others? As examples: Do Presidents and Kings warrant priority in cadaver organ allocation over ordinary citizens? Are rich people more deserving than the poor? Is it ethical to choose a younger over an older patient? Can children and/or mentally incompetent persons serve as living organ donors? Is it proper to market organs under controlled circumstances? Eli A. Friedman, an experienced nephrology training program director, and Medical Advisor to the American Association of Kidney Patients, has collected 24 difficult cases that focus on these and other vexing though common stressful issues faced by those who manage kidney patients. Using a novel approach to each case, the opinions of lawyers, nephrologists, patients, and a transplant surgeon are proffered sequentially. Friedman asks and then answers searching questions arising from the debate. The quality of information presented is positively flavored by the fact that three of the respondents (one an attorney) are kidney transplant recipients. Members of the kidney team, those immersed in seeking truth in medical ethics, and all participating in exploring the legality or ethical basis of organ replacement will find this book pertinent to their effort.

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 last 20 years has seen an enormous increase in our knowledge about the management of patients with terminal renal failure. Despite this, even the most successful dialysis and transplant patients require long term specialist supervision so that renal units will have an incremental work load until the death rate of patients undergoing treatment equals the rate of intake of new patients. Furthermore, innumerable conditions which were once regarded as contraindications to therapy may no longer be seen in this light, so that the number of new patients coming forward for treatment each year is increasing rapidly. Dialysis and transplantation are expensive forms of treatment, in terms of staff, facilities and consumables, and it is therefore inevitable that there will be problems in providing treatment for all who need it. These will be particularly acute in times of economic crisis. This book contains the proceedings of a conference which was set up to explore the difference between the supply and the demand for treatment in the United Kingdom, to compare the situation with that in other countries, to explore possible solutions and possibly assign responsibility for the shortfall and to examine the practical and moral implications of our failure to treat the treatable.

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."

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.

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 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 aim of the INTERNATIONAL YEARBOOKS OF NEPHROLOGY is to publish every year a volume to keep nephrologists up to date on all the rapidly changing areas of nephrology. Each volume will be published by the end of each calendar year which corresponds with the annual meeting of the American Society of Nephrology. Each issue of the INTERNATIONAL YEARBOOKS OF NEPHROLOGY will be divided into sections; each section will have different primary focus every year, depending upon what area is of greatest interest at the time. In other words, each annual volume will deal with what is truly current in nephrology. All the authors appointed for the chapters of the INTERNATIONAL YEARBOOKS OF NEPHROLOGY are known experts in the field who will give an objective review of the topic up-dating the readers on the world-wide literature. A crucial point for the success of the INTERNATIONAL YEARBOOKS OF NEPHROLOGY is the list of the references at the end of each chapter. We have asked all authors to provide a complete, accurate and up-to-date list of important references. In order to guarantee the most up-to-date yearbook, very rapid production is mandatory. Rapid publication can be obtained only with camera-ready manuscripts for direct photo-offset reproduction. Thus we have agreed to use photo-offset printing for the series. For the first issue of the series, the INTERNATIONAL YEARBOOK OF NEPHROLOGY 1989, the Editorial Board has focused attention on the latest and most important scientific and clinical advances in nephrology.

Blood pressure control is central to all bodily functions. There are many points in the multifaceted cybernetic system wherein hypertension may be produced. Hypertension is a 'young' disorder whose existence has been known for less than a century. It is not only extremely prevalent among every popula tion, but also deleterious to the health of mankind. The more we understand about hypertension's harmful effects, the more urgent is the need for its effective control. The kidney is the central organ that controls vascular tone and body fluid volume; these two factors are dominant in determining arterial blood pres sure. Hence, it is not surprising to find in hypertensive disorders that there are abnormalities in the kidneys, functional or anatomical, subtle or overt, that cause or are the consequence of hypertension. The first suggestion that the kidney could cause hypertension was made in 1836, before arterial pressure could even be measured, by Richard Bright. He observed that cardiac hypertrophy was often present in patients who died of renal disease. It was, however, Goldblatt and his colleagues in 1934 who opened the modern era of experimental and clinical research in renal hypertension. Since then, although far from complete, enthusiastic and intensive research efforts have greatly improved our understanding of the nature of renal hypertension."

The previous volume on Antihypertensive Agents in the Handbook of Experi mental Pharmacology, published in 1977, was edited by the late Franz Gross from the Department of Pharmacology in Heidelberg, who was one of the grand old men in hypertension research. Now, more than 10 years later, it is necessary to update this volume. From the early days of antihypertensive drug treatment, starting about 30 years ago with drugs such as reserpine and guanethidine, the pharmacology of cardiovas" cular therapy has evolved into a highly sophisticated and effective therapeutic regimen. The major breakthroughs in the 1960s were the introduction of diuretics and beta-blockers. Then, in the 1980s, came the calcium antagonists and con verting enzyme inhibitors. It can be anticipated that the next decade will see a further expansion and sophistication of blood pressure lowering drugs. This book provides a state-of-the-art discussion of chemical, experimental, and clinical pharmacological data as well as of practical experience with drugs which are presently being used or which are going to be introduced on the market in the near future. The purpose of this volume is to provide a complete discussion of antihypertensive agents. Each major class of antihypertensive drugs is treated exhaustively in a separate chapter, fully referenced with chemical formulae, and richly illustrated with figures and tables. International authorities were asked to contribute in their respective fields of expertise."

In recent years both doctors and patients have become increasingly aware that many essential drugs may induce unfortunate side-effects in susceptible individuals. The kidney is the principal route of excretion for many of these substances and may as a result become involved in pathological processes. Developments in haemodialysis and haemo perfusion may be of value in increasing the rate of excretion of potentially toxic substances but it is essential that the advantages and disadvantages of these techniques are fully appreciated by all with an interest in clinical practice. This book details the recent advances in understanding of analgesic nephropathy, interstitial nephritis, elimination of poisons and drug monitoring. Each chapter has been written by a recognized expert in the field and provides information of relevance and practical import ance to the average clinician. The developments of the last decade have emphasized that drug toxicity is a subject on which all clinicians, but perhaps especially nephrologists, should be fully informed. ABOUT TH E EDITOR Professor Graeme R. D. Catto is Professor in Medicine and Thera peutics at the University of Aberdeen and Honorary Consultant Phy sician/Nephrologist to the Grampian Health Board. His current interest in transplant immunology was stimulated as a Harkness Fellow at Harvard Medicial 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."

Combining principles of contemporary immunology with applications to immunopathology, this up-to-date volume documents new developments in the understanding of the origin of autoimmune diseases. Emphasized are cellular and molecular approaches in both organ-specific and systemic autoimmunity. A comprehensive bibliography, numerous illustrations, and tables make it an invaluable source of information for immunologists, rheumatologists, pathologists, dermatologists, and nephrologists.

Concise, recent data are presented on obstetric problems arising in patients with cardiovascular diseases (not only congenital and acquired valvular heart diseases and hypertension, but also uncommon heart lesions) and on cardiological complications encountered in pregnant women. The goal of the book is to provide obstetricians with necessary cardiological information and cardiologists with essential obstetric information to enable both specialists to make optimal decisions regarding the permissibility of pregnancy, management of pregnancy and labour, or termination of pregnancy, and selection of an adequate form of contraception in women with heart and vascular diseases. Along with recent scientific findings, the book contains practical recommendations for examination diagnosis and treatment that is effective for the mother and safe for the fetus.

The renewal of interest in peritoneal dialysis as a treatment modality for patients with end-stage renal disease was stimulated by the report of Po- povich and his colleagues in 1976 on the technique of CAPD. With the in- troduction of commercial dialysate-containing plastic bags, which mark- edly reduced the incidence of peritonitis, the use of CAPD as a primary treatment modality has increased significantly. At the present time, more than 12% of the patients undergoing dialysis in the United States are utiliz- ing CAPD; however, the use of CAPD among pediatric patients is con- siderably greater. The First International Symposium on CAPD in Children was orga- nized in order to gather together experts with experience in treating chil- dren undergoing CAPD in an attempt to exchange current information on the utilization of this emerging technique in children. Since pediatric pa- tients comprise a small percentage of the CAPD population and since lim- ited data were available concerning specific methodology and complica- tions of CAPD in children, it was hoped that an international symposium would provide a forum for an exchange of experience that would ultimate- ly lead to better adaptation and increased utilization of this technique.

Acute renal failure is undoubtedly one of the marize in one volume the recent advances on patho- most interesting and frequent syndromes observed physiology of acute renal failure, the clinical aspects by clinicians. A great number of factors may of the various forms (even those which have been acutely impair renal function, but the pathoge- disregarded in other surveys), the diagnostic tests netic mechanism by which this occurs is fre- available today in our clinical practice, the general quently unknown. Even the pathophysiology of and specific therapeutic measures and (very impor- ischaemic!toxic forms of acute renal failure re- tant, indeed), some useful suggestions for preven- mains controversial despite the huge number of tion. experimental and clinical studies. The contributors have provided clear, complete Medical management of patients with acute renal and up-to-date chapters. I am deeply grateful to failure has greatly improved in recent years, partic- them all. ularly with the use of different types of dialytic I like to express my sincere thanks to Dr. A.J.

We would like to take this opportunity of expressing our sincerest thanks to the many persons who have made adrenal tissue and related materials available to us for our work. Our especial gratitude is extended to Drs. J. J. Brown, A. Lever and J. I. S. Robertson of the M.R.C. Blood Pressure Unit, Glasgow, Dr. J. K. Grant, Royal Infirmary, Glasgow, Professor R. B. Welbourn and Dr. W. Kelly, Royal Postgraduate Medical School, Drs. D. B. Grant of Great Ormond Street, J. Ginsberg, Royal Free Hospital, D. C. Anderson, Hope Hospital, Salford, C. R. Edwards, St. Bartholomew's Hospital and Professor I. Doniach (for merly of the London Hospital) and Messrs. J.-c. Gazet, A. McKinna and P. Greening, Royal Marsden Hospital, London. The preparation and presentation of the material and the results would not have been possible without the help of Dr. P. Monaghan and his Electron Microscopy Unit, Ludwig Institute for Cancer Research (London Branch), Sutton, Mrs. Mitchell and her Histology Team, Royal Marsden Hospital, Sutton, Mr. K. Moreman of the Photographic Department of the Royal Marsden Hospital and Institute of Cancer Research, London and Mr. M. Hughes for graphics. Particular thanks are due for the untiring efforts and assistance ofMr. J. Ellis and Mrs. D. Corney of the Ludwig Institute for Cancer Research (London Branch), Sutton, for most of the photographic and secretarial work respectively. Professors G. Dhom and E. Mausle kindly provided material for Figs."

Ethical Problems in Dialysis and Transplantation presents an overview of issues with which nephrologists and decision makers are confronted in their daily practice. The search for a universal system of ethics and theories of justice are addressed. Furthermore the work provides a normative ethical discussion of ways of distributing resources with a view to selection and commercialization. Others chapters discuss a philosophical and religious analysis of stopping treatment and the clinical and ethical aspects of stopping treatment in dialysis. Different views from different countries on the subject of dialysis and transplantation are covered including the views expressed by contributors from India, Africa, Japan, Great Britain and China. The work presents the clinician with a guide to the ethical considerations underlying the treatment of dialysis and renal transplantation patients.

Clinical Management of Renal Transplantation presents The Belfast City and University Hospital experience in renal transplantation. Over the years, the Belfast Renal Transplant Unit has acquired considerable experience in all aspects of renal transplantation which have led to excellent results. The team working in the Belfast Renal Transplant Unit has built up an outstanding reputation which has become widely known. This volume is a comprehensive, practical reference work for senior medical students and nurses as well as for the established nephrologist and transplantation surgeon. It provides a clear and concise picture of the care needed by patients who are being prepared for renal transplantation or who have recently received a kidney transplant.

More than half a million people worldwide are now sustained by renal replacement therapy, mainly hemodialysis at a cost exceeding USD 30 billion per year. Each case of ESRD that is delayed or prevented saves funds that may be applied to other aspects of health care. Edited by an internationally renowned nephrologist, Prognosis for Kidney Disorders provides a timely summary of exciting work in progress directed toward renoprotection and of ultimate interdiction of ESRD.
Suitable for researchers and clinicians, Dr. Morrell Michael Avram has collected and commented on promising initiatives likely to enter everyday practice in the immediate future. Suitable for renal trainees, experienced kidney doctors, nurses, nutritionists and cardiologists.

Is the nephrology community facilitating excess cardiovascular deaths in patients with kidney failure and anemia by treating to a subnormal hematocrit? Why have clinicians and nephrologists permitted health insurance companies and the government to decide when anemia therapy should begin in persons with progressive kidney failure? Is iron the only variable that can be manipulated to maximize response to recombinant erythropoietin? Are we using too much intravenous iron in kidney failure patients, and is oral iron supplementation worthless in sustaining iron stores during long-term erythropoietin treatment? When does left ventricular hypertrophy begin to emerge in patients with progressive renal disease and is there convincing evidence that anemia is a significant cause of LVH in this setting? Is darbepoetin alfa, a new novel, long-acting erythropoietin, really superior to recombinant erythropoietin? This book is a compilation of proceedings from a conference in Brooklyn convened to address these and other controversial and unresolved issues in renal anemia management.

Glomerulonephritis has always been regarded as a complex subject. Different forms o f the disease c a n cause death in a matter o f weeks, nephrotic syndrome which might or might not prove responsive to steroid therapy, or no symptoms a t all. Improved pathological te- niques and criteria have permitted a more accurate diagnosis and prognosis to be established for many patients. With increased und- standing of the immunological mechanisms involved it has become apparent that many patients presenting with a variety of symptoms and signs m a y have glomerulonephritis as their primary pathological process. This book examines the clinical, pathological and aetiological factors involved in the common forms o f glomerulonephritis. Each chapter has been written by a recognized expert in the field and provides information of relevance and practical importance to the average clinician. The developments of the last decade have emp- sized that glomerulonephritis is no longer a matter only for the nephrologist but a subject o n which all clinicians should be well informed.