Volume 5 of Contemporary Nephrology summarizes major advances in 15 different areas of nephrology. As in previous volumes the different chapters constitute up- of the discipline contributed by individuals dates in both basic and clinical aspects with in-depth expertise in their respective areas. We are grateful to the authors for their outstanding contributions to this fifth volume. Drs. Reuss and Cotton review in Chapter 1 new advances in our understanding of water transport in epithelial tissues responsive to antidiuretic hormone. In Chap- ters 2 and 3 Dr. Knox and Dr. Schoolwerth and their associates summarize respec- tively new information in the areas of renal hemodynamics and electrolyte excre- tion, and renal metabolism. Chapter 4, written by Drs. Laski and Kurtzman, updates recent developments in the regulation of acid-base balance in health and disease. Chapter 5, contributed by Drs. Sutton and Cameron, provides the reader with a detailed account of progress in the area of mineral metabolism. In Chapter 6, Dr. Campese examines the contribution of sodium, calcium, and neurogenic factors in the pathogenesis of essential hypertension. The immunological aspects of renal disease are clearly discussed by Dr. Couser in Chapter 7. New developments in this field are emphasized and should provide the reader with a clear understanding of the direction in which this field is moving. Drs. Humes and Messana (Chapter 8) discuss selected areas in which new developments have occurred in our understand- ing of acute renal failure and toxic nephropathy.

Ever since Richard Bright discovered the link between kidney disease and cardiac hypertrophy inhispioneeringworkin 1827, thefieldofrenovascularandrenal parenchy matous hypertension has been a transatlantic adventure. Towards the end of the nine teenth century, Tigerstedt and Bergman discovered that the kidneys contain a factor whichraisedbloodpressurewheninjected intointactanimals. Theynamedthesubstance renin, which is now known as the crucial enzyme activating the angiotensin aldosterone system, which is so pertinent in the regulation of blood pressure and kidney function. After this crucial European contribution to the field, Harry Goldblatt at the Cleveland Clinic demonstrated in his classical experiments that reduction in renal blood flow, by placing a clamp at the major renal artery, could induce sustained hypertension. These discoveries established the role of the kidney in certain forms of hypertension which are now classified as renovascular and renal parenchymatous hypertension. These fundamental concepts suggested - based on experimental evidence - that restoration of blood flow or nephrectomy in unilateral parenchymatous disease would lead to blood pressure normalization in these patients. Indeed, as early as the first half of this century, a report appeared demonstrating blood pressure normalization in a child with fibromusculardisplasiaofthe right renalartery after nephrectomy. Advances in surgical techniques later allowed reconstructive renovascular surgery and therefore a more appropriate form of therapy of the disease. In the late seventies Andreas Grtinzig initiated another European contribution to renovascular hypertension by introducting the procedure of percuteaneous transluminal angioplasty, an elegant catheter technique allowing non-surgical therapy of renovascular disease."

This Pediatric Nephrology series is a focus on salient points which at the time of each annual seminar are of importance to the practicing pediatrician and nephrologist, the clinical researcher, and basic researcher interested in clinical problems. Hence the format of selected papers and panel discussions to capture the tenor of the times. More thorough coverage of many of the subjects can be found in current journals and textbooks listed in the authors' references. Those searching for the conventional should look there rather than here since our aim is not to cover each subject in its entirety but to secure attention to the controversial aspects of the subjects, dispel the notion that there is one answer to a question, and raise the level of inclination toward dynamic problem solving. The basic subject chosen this year reflects dominant concerns this year and the participants chosen--speakers and discussants--represent certain views relevant to the subject at this time. To reflect the tempo and flavor produced by this unique blend, the discussions are included almost verbatim. For some this means readability; for others, excess verbiage. The careful reader will notice that I have been the chairman of all sessions and have moderated all discussions. This is in keeping with our aim to ferret out interrelated basic questions and varying answers to the subjects--seen as related in problems and solutions. In the discussions, all names have been deleted.

The Final Report of the USA CAPO Registry summarizes eight years of observation and analysis that reflects the experiences of 485 clinical centers and over 25,000 CAPO patients. As such, it offers a wealth of information, available here for the first time to interested parties around the world. Because the National Institutes of Health was quick to see the potential of CAPO as a promising therapy for patients with end stage renal disease, the Registry project was begun soon after its introduction into clinical practice in the USA. Accordingly, the Registry offered the nephrology community in the United States a special opportunity to study this emerging new therapy in some detail, an opportunity not previously available for any other form of dialysis. As will be seen in this report, the result of this early and intensive research effort has been the development of a vast amount of clinically important information regarding the utilization, safety, and efficacy of this important dialytic therapy.

The year was 1943. As a third-year medical student at Stanford, I was about to witness the beginning of a medical miracle. Dr. Arthur Bloomfield, Professor of Medicine, had selected my patient, a middle aged man, who was dying of acute pneumococcal pneumonia, as one of the first patients to receive miniscule doses (by today's standards) of his meagre supply of a new drug - penicillin. The patient's response amazed everyone especially this impressionable medical student. The rest of the story is history. With one stroke, the introduction of penicillin removed from the medical scene the 'friend of the aged' - lobar pneumonia. The consequences, which no one could have imagined at the time, are still becoming manifest as other 'miracles' such as respirators, artificial kidneys and many potent new antibiotics have come upon the scene. All of us are aware that these miracles have created a variety of new challenges around the states of dying and near dying. We have no easy answers for these problems. Nevertheless as dialysis techniques, especially CAPD, are applied more widely to the treatment of the elderly, the task of helping the patient meet death with dignity becomes increasingly important and vexing because once begun, dialysis is difficult to terminate.

This book is a gift from the international community of amyloid friends, presented to Professor Dr. Enno Mandema on the occasion of his retirement from the University of Groningen, the Netherlands. It is the "precipitation" of up to date knowledge of amyloidosis, as presented at the International Course on Amyloidosis in Groningen, on the 10th and 11th of October 1986. Twenty years ago, Professor Mandema invited a group of scientists, who were studying the various aspects of amyloidosis from different points of view, to discuss their mutual interest in the subject. This "First International Symposium" was held for five days in September 1967. It was a wonderful experience for the participants, as most of them had until then only read each others work in the literature. The proceedings of that symposium, which contained the "lively" dis cussions, became a text-book for the following years. Research continued, and while the book was still in preparation, the revolutionary method of "water-soluble amyloid" was published. In the following years, different amyloid proteins were discovered and the mo lecular basis of the different amyloid syndromes was elucidated. The increase in knowledge parallelled the availability of modern, ingenious and also rapid methods in the biomedical sciences."

With contributions by D. Albrechtsen, O.H. Bentdal, H. Bondevik, I.B. Brekke, P. Fauchald, J.G. Fjeld, A. Flatmark, A. Foss, A. Hartmann, H. Holdaas, R. Innes, A. Jakobsen, N.E. Klow, B. Lien, O. Oyen, P.F. Pfeffer, K. Rootwelt, G. Sodal and K. Vatne

During the last few years, renal hypertension has become a subject of increasing importance. The development of improved radiological techniques, notably intravenous and intra-arterial digital subtraction angiography, has made the diagnosis of renal artery stenosis more reliable, while advances in vascular surgery and the introduction of percutaneous trans luminal angioplasty have caused major changes in clinical practice. The increasing use of such potent antihypertensive agents as the angiotensin I converting enzyme inhibitors has empha sized the problem of renal artery stenosis in older patients with wide spread vascular disease as well as improving the prognosis of patients with accelerated hypertension. This book examines the surgical and medical aspects of renal hyper tension in the light of these recent advances. 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 emphasized that renal hyper tension is no longer a matter only for the nephrologist but a subject on which all clinicians should be well informed."

This is the 11th of the Pediatric Nephrology series created to help us be in touch with developments which are relevant to the problems we face daily in clinical practice and the questions we ask and try to answer in clinical and experimental research. Like volume IX, this one focuses on one of the subgroups to which we are committed--the neonates' special fluid and electrolyte requirements. This volume has more on blood pressure and renal function and looks at the hormonal regulators. There is greater depth about intoxications and nephrotic agents, congenital disorders and mineral metabolism. The exchanges were stimulating and the controversies were brought out without need of much of my usual prodding. At Julie Ingelfinger's suggestion, at the end of each panel discussion I have added a comment to highlight the main points as I see them. Otherwise, the format remains as in past editions: the papers given related to the four major topic areas, each followed by panel and registrant discussion. Although the transcription is almost verbatim, you will not find the names of the discussants, purposely omitted to ease my editorial work and to encourage everyone to speak candidly. Some of the questions and answers are those submitted to the panelists after the sessions, incorporated here by request. Also, frequent references are made to others' work but their names have been omitted.

What regulation shall we have for the operation? Shall a man transfuse he knows not what. to correct he knows not what. God knows how (l)? Dr. Henry Stubbs Royal College of Physicians circa 1670 If dialysis therapy were a new phannaceutical product being evaluated by the FDA now, it might not be approved for marketing. The recommended dose, its potential toxicity, the side effects of under-or over-dialysis as well as its efficacy have been the subject of very few studies. The high mortality rate associated with the treatment may raise a few eyebrows. That it is a life-saving modality of treatment is undoubtedly true for more than 100,000 patients in the United States and for more than a million patients world wide. Because dialysis has extended the lives of many people by a variable period of time, most nephrologists have "rested on their laurels" and did not vigorously pursue studies to optimize these treatments. But facts have a way of intruding in all our lives and the facts are that the overall mortality rate of dialysis patients in the United States is rising and stands close to 25% per year and is closer to 33% per year for patients between the ages of 65 and 74 (2). These mortality figures are considerably higher for age-adjusted dialysis populations in Europe and particu larly in Japan, and certainly for the age-adjusted nonnal population."

Renal transplantation is now accepted as the treatment of choice for patients with end-stage renal failure. During the last decade both patients and graft survival rates have increased significantly and when assessed at one year are now greater than 90% and 80% respectively. These marked improvements have occurred at a time when increasing numbers of patients in the older age groups and with more complex forms of renal disease are being accepted for transplantation. The reasons for the improved clinical results are not fully understood but are probably linked with changes in blood transfusion policy, tissue typing policy and drug therapy. These topics, together with immunological monitoring and details of how to treat the highly sensitized patient, are fully covered in this volume. All the chapters have been written by recognized experts in their field. Not only are the recent advances well documented but the likely future developments in management are identified and discussed. As renal transplantation is now the single most common of treatment for renal failure, the information presented in this form volume should prove of value to all with an interest in current clinical practice.

This is a book about renal cysts and cystic kidneys. Its contributors have created a resource of current information in a field that once aroused only curiosity, but that now stands at the leading edge of molecular nephrology. Its authorship includes 'oldtimers', who bring the wisdom of experience, and 'newcomers', whose presence attests to the contributions made by the investigative and technological advances of the past decade. Its text is organized to carry the reader from renal cyst to cystic renal disease. Each of its chapters defines or explores a challenge or an advance. Cells that line renal cysts are diverse in structure, type, and perhaps function. The cysts themselves lie within an interstitium that is not normal and may influence cyst development and growth. Experimental analogs of human disease offer increasing opportunities to basic researchers to examine, in sequence and under controlled circumstances, those events that favor nephron dilation, cyst growth and ultimate renal failure.

During the last decade facilities for treating patients with end-stage renal failure have expanded in all Westernized countries. Partly as a consequence, interest has been stimulated in many multisystem dis- eases which may progress to chronic renal failure. Some of these diseases such as diabetes mellitus are common but still have con- troversial aspects to their investigation and management. Others such as lupus nephritis are relatively rare but respond well to recent advances in therapy. In addition to diabetes mellitus and lupus nephritis this volume has chapters on multiple myeloma and Henoch-Schonlein purpura. All the chapters have been written by ackl10wiedged experts who have emphasized the practical aspects of patient management. The infor- mation contained in this volume should thus prove of interest not only to nephrologists but to all practising clinicians. VII ABOUT THE EDITOR Professor Graeme R. D. Catto is Professor in Medicine and Thera- peutics at the University of Aberdeen and Honorary Consultant Physician/Nephrologist to the Grampian Health Board. His current interest in transplant immunology was stimulated as a Harkness Fellow at Harvard Medical School and the Peter Bent Brighton Hos- pital, Boston, USA. He is a member of many medical societies includ- ing the Association of Physicians of Great Britain and Ireland, the Renal Association and the Transplantation Society. He has published widely on transplant and reproductive immunology, calcium metab- olism and general nephrology.

This book includes the proceedings of the 2nd International Meeting on Cur- rent Therapy in Nephrology held in Sorrento, Italy, May 22-25, 1988. The book provides a comprehensive update on new therapeutic strategies in the broad field of Nephrology. The reader will receive information on advances in treatment of glomerulonephritis, new dialysis techniques and progress in renal transplantation. In addition, sections deal with provocative experimental ap- proaches to treating renal disease. Topics include: cyclosporine in treatment of nephrotic syndrome, plasma ex- change in ARF, treatment of beta-2 microglobulin amyloidosis, nutritional of dialytic adequacy revisited after assessment in patients on RDT, standards development of biocompatible membranes, drug interaction with cyclosporine, renal transplantation in elderly recipients, and renal transplantation with elderly donors. A special effort was made to recruit contributors among the most important scientific authorities in their respective fields: we are grateful to Drs. Cameron, Lamm, Isemberg, Meyrier, Niaudet, Brynger, Lundgren, Fauchald, Cockburn, Gotch, Kopple, Cheung and Horl for having accepted our invitation. We are also indebted to all other authors who participated in the meeting and submitted their original papers for publication. I.

When the external Quinton-Scribner arteriovenous shunt was developed in 1960, and, a little later, the internal Brescia-Cimino arteriovenous fistula was developed as a vascular access for hemodialysis, thereby making possible regular dialysis therapy of chronic uremic patients, many nephrologists became surgeons, having learned the type of vascular surgery related to hemodialysis quite well. The same series of events occurred with regards to peritoneal dialysis with the introduction of the Tenckhoff catheter and the need for gaining a permanent access to the peritoneum for chronic ambulatory peritoneal dialysis (CAPD) therapy. With time, however, problems relating to vascular and peritoneal access have forced many nephrologists to give up their surgery; meanwhile, many surgeons have become quite expert in some sophisticated techniques relating to dial ysis (e. g., vessel grafting, prosthesis implantation, etc.). Today, whether or not involved in this type of surgery, both nephrologists and surgeons remain interested in knowing all available access devices for dialysis as well as the surgical techniques involved. However, all nephrologists involved in dialysis must know how to prevent or treat complications related to dialysis access. Thus, it appeared to me to be quite advisable to have a book in my series, Topics in Renal Medicine, dealing with vascular and peritoneal access for dialysis.

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."

Renal stone disease remains a common clinical problem. Patients m a y attend either medical or surgical clinics and n o t infrequently present as acute abdominal emergencies to general practitioners, physicians, surgeons and even gynaecologists. Recent urinary calculi continue to cause considerable morbidity despite the recent advances in our understanding of the pathogenesis of the different types of stones involved and despite improvements in t reatment- by appropriate drug therapy, by ultrasound techniques and by lithotripsy. This volume discusses the investigation and management o f patients with calculus disease. Each chapterhas been written by a n experienced clinician and provides information of considerable relevance and importance for all doctors engaged in clinical practice. The technical developments o f the last few years have clearly demonstrated that renal stone disease, even when recurrent, should be an uncommon cause of chronic renal failure. Knowledge o f the recent developments in this field is important for all practising doctors and even more important for their patients.

'Where are all these kidney patients coming from? A Atchley and others studied the effects of hypertension, endocarditis, and circulatory diseases on the kidney and few years ago we never heard of kidney disease and now you are speaking of patients in the hundreds of thou spawned successive generations of alert clinical investi sands and indeed potentially millions'. My reply, not gators who began to chronicle the natural histories of a meant to be grim, was 'From the cemetery, Sir'. This is wide variety of kidney diseases. Quantitative studies of a summary of some Congressional testimony I once renal function flourished under a school headed by Homer Smith, and surprisingly precise techniques were gave on behalf of extending kidney disease under Medi care. Where indeed were all the patients with kidney developed for studying a whole range of explicit nephron disease in the United States before World War II? They functions. Imagine the joy with the advent of catheteri were certainly not under the care of Nephrologists! zation to be able to apply extraction ratios and the Fick Nephrology was not listed in the questionnaires for any principle in a precise way to an organ such as the kidney State or the American Medical Association as a subspe by sampling arterial blood, venous blood and the output of the urine! One had a quantitative handle on the entire cialty or even as a special interest.

Serious disturbances of fluid and electrolyte balance are frequently encountered in acutely ill patients; somewhat less often in the chronically sick. There seems to be a trend for such cases to increase, due probably to an increase in major surgical procedures on older patients whose renal function is less than adequate. There are already many publications dealing with the physiology of the homeo stasis of fluid and electrolytes, and others dealing with the clinical aspects of the subject. It is often assumed that a knowledge of the basic principles of physiology will enable the doctor to prescribe suitable intravenous therapy. In practice this is often found not to be so and the evidence for this is the frequency of calls for help with electrolyte problems from well-qualified and experienced doctors who are undoubtedly equipped with adequate or even excellent knowledge of the basic It is not an unusual observation that knowledge of theory and principles involved. principles does not necessarily lead to successful practice in this or any other art or craft. Most doctors already possess knowledge of the physiology of the internal envi ronment, but some are aware of being unable to deal effectively with clinical problems related to fluid and electrolyte disturbances and seek guidance to translate theoretical knowledge into practice."

In November 1986, I was invited to attend a symposium held in Barcelona on Diseases of the Pericardium. The course was directed by Dr. J. Soler-Soler, director of Cardiology at Hospital General Vall d'Hebron in Barcelona. During my brief but delightful visit to this institution, my appreciation of the depth and breadth of study into pericardial diseases, carried out by Dr. Soler and his group, grew into the conviction that these clinical investigators have accumulated a wealth of information concerning pericardial diseases, and that investigators and clinicians practicing in English speaking countries would greatly profit from ready access to the results of the clinical investiga tions into pericardial disease carried out in Barcelona. The proceedings of the Barcelona conference were published in a beauti fully executed volume in the Spanish language edited by Dr. Soler and pro duced by Ediciones Doyma. Because I believe that this work should be brought to the attention of the English speaking scientific and clinical com munities, I encouraged Dr. Soler to have the book translated into English. I knew that this task could be accomplished and that the book would be trans lated into good English without change of its content. My confidence was based upon a translation of my own book, The Pericardium, into Spanish undertaken by Dr. Permanyer, who is a contributor and co-editor of the pre sent volume."

Almost every practising doctor will admit to difficulty in knowing how best to investigate, treat and advise the pregnant patient with renal problems. These doubts and difficulties may be exacerbated if the patient seeks pre-pregnancy advice - would a possible pregnancy cause a deterioration in renal function, what are the risks of the pregnancy for mother and baby? As the general public become more informed on medical matters these questions are being asked more frequently and doctors must be prepared to offer advice which is based on detailed factual knowledge. This book examines some of these increasingly common clinical problems. Each chapter has been written by a recognized expert in the field and provides the type of specific information now expected by discerning patients. The advances in treatment of the last decade clearly indicate that a knowledge of pregnancy and renal disorders is essential for doctors in many branches of medical practice.

During recent decades, it has been firmly documented that chlamydiae are com mon and important pathogens in humans and animals. In humans, chlamydiae are known to cause trachoma (which is still one of the major blinding diseases in the world) and are also one of the most common etiological agents of sexually transmitted diseases and the sequelae thereof, such as infertility. In the last few years, it has also become evident that chlamydiae, i.e., the so-called TWAR agents, are common respiratory tract pathogens. Chlamydiae are also important pathogens in birds and lower mammals, in whom they cause a variety of infectious conditions, a spectrum which has in creased every year. Some of these infections occur as zoonoses, e.g., psit tacosis/ornithosis and, as recently discovered, abortion. Know ledge of the molecular biology and immunobiology of chlamydiae has expanded rapidly during recent years. Insight into the pathophysiology of chla mydial infections has also increased, and new methods for the diagnosis of chlamydial infections have been introduced. The importance of establishing control and preventive programs for chla mydial infections has become obvious in order to combat the present chlamydial epidemic. We hope that this book can usefully serve those who want to increase their general knowledge of Chlamydia and that it can act as a handbook and reference source for those involved in chlamydial research as well as for those working with chlamydial infections in medical and veterinary clinical disciplines, includ ing clinical laboratories."

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.

The European School of Oncology came into existence to respond to a need for information, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidiscipli nary approach which is difficult for the Universities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on future developments in specific fields of on cology."