The purpose of this book is to provide information for the nephrologist to gain a perspective on the medical, scientific, and technical aspects of reprocess ing of hemodialyzers. The book is also designed to serve the needs of the associated medical, nursing, and technical staffs of dialysis facilities for data on reuse of hemodialyzers. As an information source, the book will prove to be useful for those who may be considering reprocessing of dialyzers, as well as persons who are currently involved in this aspect of the practice of nephrology. We have focused on the clinical and technological aspects of hemodialyzer reprocessing and have not dealt with socioeconomic considerations. We do wish to share with physicians performing hemodialysis several observations we have made as a result of assembling this volume. We believe that hemodialyzer reuse has had a beneficial impact on the quality of care for hemodialysis patients in consideration of the following factors. There is an increased awareness of membrane biocompatibility issues that has been brought to the forefront with the application of reuse. Utilization ofhemodialyzer reprocess ing has enabled nephrologists . to compare the effect of various measures on biocompatibility when the patient is exposed to either a new or a reprocessed device. Previously, few readily available comparisons existed. In the practice of dialysis, water quality has always been of considerable importance. With the advent of widespread hemodialyzer reprocessing, the issues of water bacteriology and water quality have become more prominent."

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."

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.

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.

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.

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.

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.

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

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 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.

'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.

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.

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."

We are pleased to present to our readers the Proceedings of the Fourth International Workshop on Phosphate and Other Minerals which was held in Strasbourg during June 22-24, 1979. It was hosted by Professor Henri Jahn, Professor of Medicine and Chief, Department of Nephrology at the University of Strasbourg. These Workshops have become a tradition in the scientific scene of mineral metabolism. The meetings have been providing a unique framework for close interaction between scientists from various disciplines, such as nephrologists, endocrinologists, bio chemists, nutritionists, and those dealing with bone metabolism. The Workshops also created a forum for the delivery of original information, as well as state-of-the-art presentations on exciting topics of current interest in this evergrowing field of phosphate and mineral homeostasis. The Fourth International Workshop was attended by three hundred scientists from 15 countries including Austria, Canada, Denmark, England, France, Germany, Holland, Israel, Italy, Japan, Sweden, Switzerland and the United States of America. The topics discussed included those dealing with the renal handling of phos phate, calcium and magnesium, intermediary phosphate metabolism and phosphate homeostasis in health and disease. Two symposia were also presented: one dealt with nephrolithiasis and its rela tion to phosphate and the other with bone metabolism. In addition to 22 presentations by invited speakers, the Workshop provided 46 oral and 93 poster presentations selected from over 250 abstracts submitted to the Organizing Committee."

Peritoneal dialysis represents an internal technique for blood purification. In this dialyzer the blood path, the membrane, and the dialysate compartment are provided by nature. The developments of chronic peritoneal catheters, auto mated cycling equipment, solution preparation by reversed osmosis, manipula tions of transport with drugs, and the experiences with continuous ambulatory peritoneal dialysis and continuous cycling peritoneal dialysis have increased the interest in peritoneal dialysis. Publications related to peritoneal dialysis exceed 400 annually. The Peritoneal Dialysis Bulletin represents a new journal devoted to peritoneal dialysis developments. The Third International Symposium on Peri toneal Dialysis is to be held in Washington, D.C. in 1984. From this meeting it is likely that an International Society for Peritoneal Dialysis will emerge. This book is meant to provide an overview of the state of the art of peritoneal dialysis. Many clinicians are making extensive commitments to peritoneal dialysis for the first time. Nephrologists, physiologists, pharmacologists, biomedical engineers, and even physicists are involved in studies to better understand peritoneal dialysis. The complexities of peritoneal dialysis and the peritoneal membrane are becoming apparent. Studies of peritoneal dialysis increase under standing of the anatomy and physiology of biological membranes and of factors influencing the passive movement of solutes across the microcirculation and related structures. Peritoneal dialysis provides a 'window' to the visceral micro circulation in animals and humans. Peritoneal dialysis may be useful to treat problems other than renal failure."

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."

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.

Anti-native DNA antibodies and DNA are present in cryopreClpItates from patients with systemic lupus erythematosus and some other cryoglob ulinemic states. The data suggest that these antibodies may be bound in immune complexes. The demonstration of native DNA in these precipitates raises the likelihood that they represent specific antigen in these complexes. Whether or not these complexes play a pathogenetic role in nonlupus inflammatory diseases remains to be demonstrated. References Aarden, L. A., de Groot, E. R., and Feltkamp, T. E. W., 1975, Immunology of DNA. III. Crithidia luciliae, a simple substrate for the determination of anti-dsDNA with the immu nofluorescence technique, Ann. N.Y. A cad. Sci. 254:505. Agnello, V., Winchester, R. J. and Kunkel, H. G., 1970, Precipitin reactions of the Clq component of complement with aggregated 'Y-globulin and immune complexes in gel diffusion, Immunology 19:909. Anker, P., Stroun, M., and Maurice, P. A., 1975, Spontaneous release of DNA by human blood lymphocytes as shown in an in vitro system, Cancer Res. 35:2375. Bankhurst, A. D., and Williams, R. C., 1975, Identification of DNA-binding lymphocytes in patients with systemic lupus erythematosus, ]. Clin. Invest. 56:1378. Bluestone, R., Goldberg, L. S., Cracchiolo, A., and Barrett, E. V., 1970, Detection and characterization of DNA in mixed (IgG-IgM) cryoglobulins, Int. Arch. Allergy Appl. Immunol. 39:16."

The first edition of this book was well received by updated. The two of us have made further collab orative efforts to present a better understanding of medical students, graduate students, and clinicians interested in furthering their understanding of basic the function of the kidney in conjunction with the principles of renal physiology. Most of the reviews most recent anatomical findings. of the first edition and comments from the various The second edition consists of 13 Chapters and 3 instructors who used the book were very positive Appendices. As in the first edition, the anatomical and complimentary with regard to the presentation description of the kidney is incorporated into the of the physiological information and the use of the various chapters dealing with kidney functions. Most system analysis approach to describe renal function. of the anatomical information was written by Wil These positive and encouraging comments over the helm Kriz. The physiological information was writ past nine years, since the publication of the first ten by Esmail Koushanpour, except for Chapter 12 edition, gave us the impetus to consider the prepa which was jointly written. Chapters 1 through 3 were ration of a second edition."