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.

'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.

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.

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."

The mechanisms by which animals regulate the volume and composition of their body fluids has long had a particular fascination for students of biology. As a consequence, the subject can lay claim to an impressive record of ground breaking scientific achievements as well as a provocative body of philosophical speculation concerning the role of the system in the origin and evolution of life. Indeed, the entire concept of homeostasis on which so much of o r current biologic thinking is based, derives from Claude Bernard's pioneering exploration of the forces that determine the composition of this 'internal sea'. Other seminal achievements credited to this area of inquiry include the first description of a genetically transmitted human disease (familial neurogenic diabetes insipidus); the first isolation sequencing and synthesis of a peptide hormone (vasopressin and oxytocin); the first demonstration of peptide hormone synthesis by way of a larger protein precursor; the first description of resistance to the biologic actions of a hormone (nephrogenic diabetes insipidus); and the conceptual realization of the unique counter-current mechanism that permits concentration of the urine. This record of far reaching and fundamental advances has been distinguished by many fruitful inter actions between clinical and basic science."

Urinary tract infection remains one of the most common reasons for an individual seeking medical advice. Although the associated morbidity varies widely in adults, such infections are less common but may constitute severe, life-threatening illness in children and in the elderly. Diagnostic tests and treatment have been rationalized in recent years but many practising doctors still have difficulty in appreciating the patho-physiological principles involved. Particular difficulty is often experienced when treating patients with recurrent urinary tract infections, covert bacteriuria, vesico-ureteric reflux, elderly patients and those with indwelling catheters. These topics are fully discussed in this volume. Each chapter has been written by a recognized expert and practical aspects of patient management have been emphasized. The information presented in this volume should 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 Phy sician/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."

Decoding the significance of proteinuria as an indicator of severity or prognosis in kidney disease is a stimulating challenge to students and practitioners of nephrology. Sir Richard Bright in 1827 associated pro with the disease that bears his name. In the subsequent more teinuria than a century and a half, however, the meaning of the linkage between proteinuria and renal disease remains elusive. Proteinuria is discovered on routine urinalysis in about 10 million Americans, most of whom express no symptoms of kidney disease, each year. From the studies of Robinson (updated in these pages), we know that proteinuria, per se, can be present for 20 years without change in re nal function, as described in orthostatic proteinuria. By contrast, pro teinuria may be the harbinger of swift kidney destruction, rarely cul minating in clinical collapse, a syndrome typifying "malignant proteinuria" as detailed herein by Avram. Although proteinuria is ubiquitous, an orderly management strategy for rational handling of proteinuria of less than nephrotic range is lack ing. Separation of tubular proteinuria and transient proteinuria of fever is now possible routinely. This book provides a record of the contribu tions of investigators and clinicians whose work forms the substrate for production of understanding and, ultimately, marching orders for prac titioners seeking optimized management for their proteinuric patients."

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 haemoperfusion for certain types of poisoning, the basic principles ofhaemodialysis 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 extracorporeal 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."

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."

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.

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 behavior of the kidney in normal pregnancy, as well as in complicated pregnancy, is a very interesting, but still in many ways an unknown topic in renal medicine. It is undoubtedly difficult to determine, even in normal women, the behavior of renal hemodynamics throughout gestation, since the fear of impairing a new life (i.e., the fetus's life) will limit, for ethical reasons, the use or the frequent repetition of diagnostic tests on the mother. On the other hand, the study of complicated pregnancy even for diagnostic purposes (for planning adequate treatment), except in a few countries that are known for the advanced health education of the population, has to face serious difficulties. First of all, pregnant women usually seek the help of an obstetrician when gestation is already in an advanced stage. This makes it difficult to determine when and how asymptomatic signs of any disease discovered during pregnancy have first occurred. A second difficulty is that frequently the patient does not know whether a given disease has preceded pregnancy. Pregnancy is a condition of young women, and a young woman frequently has never seen a physician; thus, no urine analysis or blood tests have been performed before the gestation. Not infrequently, even blood pressure has never been measured. This will make it difficult to classify hypertension discovered in late pregnancy as pregnancy-induced hypertension or as chronic hypertension in pregnancy.

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."

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.

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.

Glomerulonephritis is one of the commonest causes of end-stage renal failure worldwide. Although there have been considerable advances in the management of renal failure by dialysis and transplantation, there has been relatively little progress in its prevention. This volume sets out to review current practice in the treatment of glomerulonephritis, which is aimed both at controlling the clinical manifestations, e.g. nephrotic syndrome, and at preventing the progression to renal failure. The term glomerulonephritis covers a wide range of conditions with different immunological, histological and clinical features. This volume therefore starts with reviews of the immunology and pathology of different types of glomerulonephritis. This is followed by detailed consideration of the treatment of the commoner primary and secondary forms of the disease. There are separate chapters on special circumstances, such as glomerulonephritis in pregnancy or following renal transplantation. In each chapter, attempts are made to review the evidence for the effectiveness of treatment, based on controlled trials, immunopathological principles and the authors' considerable experience. Although some aspects of the treatment of glomerulonephritis can be found in the standard texts on renal disease, this volume provides an up-to-date, thoroughly referenced, and practical guide to management. As such, it should be of value to nephrologists and general physicians, including those in training, and to postgraduate students of nephrology.

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.

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.

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.

Cardiovascular complications are not only responsible for more than half of our patients' mortality, they also represent the bulk of everyday problems in a dialysis unit. Yet, the space allocated to them in the major textbooks covers only 2-8% of their total content. The origins of this book lie in many years of day-to-day care of dialysis patients. It gradually became clear to the author that systematic application of well-known pathophysiological principles could improve patients' conditions beyond expectations. More importantly, it appeared that world literature was mainly concerned with evaluating risk factors and that efforts to improve prognosis were concentrated on urea removal. It is important, therefore, to notice that Volume Control', the central issue of this book, is not incorporated into the Adequacy' concept. While primarily intended for dialysis doctors, the author sincerely hopes that dialysis nurses, who carry the lion's share of day-to-day responsibility for dialysis patients, will also find this book a useful and practical guide to dialysis treatment.

When the kidney fails its intended mission to manage the body 's waste products, physicians must perform multi-level and simultaneous adjustments to replicate kidney function. The management of the body 's absorption, reabsorption, utilization and excretion of calcium and phosphate requires constant fine tuning. This book provides an overview of the state-of-the-art clinical and basic science aspects of abnormal calcium and phosphate metabolism and its management.

aintaining extracellular calcium concentrations within a narrow range is critical for the survival of most vertebrates. PTH, together with vitamin D, responds to hypocalcemia to increase extracellu M lar calcium levels, by acting on bone, kidney and intestine. The recent intro duction of PTH as a major therapeutic agent in osteoporosis has directed renewed interest in this important hormone and in the physiology of the parathyroid gland. The parathyroid is unique in that low serum calcium stimulates PTH secretion. As hypocalcemia persists, there is also an increase in PTH synthesis. Chronic hypocalcemia leads to hypertrophy and hyper plasia of the parathyroid gland together with increased production of the hormone. Phosphate is also a key modulator of PTH secretion, gene expres sion and parathyroid cell proliferation. Understanding the biology of the parathyroid as well as the mecha nisms of associated diseases has taken great strides in recent years. This book summarizes the molecular mechanisms involved in the function of the para thyroid gland. The first chapter reviews the development of the parathyroid gland and the genes involved in this process as identified using genetically manipulated mice. Then the biosynthetic pathway of PTH from gene ex pression to its intracellular processing and the sequences in the gene control ling its transcription as well as those regulating mRNA processing, stability and translation are described."