Drug dosage in renal insufficiency has become an toxication. In 1975, his Poison Index was pub important facet of nephrology, a subspeciality of lished, first in German, and two years later in internal medicine which is only 30 years young but English, with supplements in 1979 and 1983. This constantly growing in scope and importance. Two volume has become an obligatory reference in more thirds of all drugs are partially, mainly, or exclu than 2500 dialysis units. sively excreted by the kidneys. In the presence of Based on GOnter Seyffart's experience and renal insufficiency, dose adjustments are therefore knowledge in this field, the plans for this book obligatory. In patients on dialysis, drug elimination matured in 1984, a logical step in view of his by this route must also be considered. untiring effort and diligence. In order to deal with As the reader of this book will discover, 20 more than 1200 different drugs and almost 4000 percent of currently used drugs are contraindicated references, 21 contributors were sollicited, while it where there is any degree of renal insufficiency, took six years to complete the work. The major and for at least another 60 percent a dose reduc share of the effort was thus left to the main author tion is required. It is obvious, therefore, that the and editor and he has produced a concise work of detailed knowledge required can never be com impressive clarity."

Hepatic Encephalopathy (HE) is a neuropsychiatric disorder resul t- ing from liver failure. HE may be associated with fulminant (acute) hepatic failure or chronic liver disease with portal-systemic shunting. The latter condition is characterized neuropathologically by astro- cytic rather than neuronal changes (Alzheimer Type II astrocytosis). The former is frequently accompanied by cerebral edema. Several hypotheses have been proposed to explain the pathogene- sis of HE. These include: 1. A toxic action of a substance (or substances) such as ammonia on brain function 2. A deficit of cerebral energy metabolism 3. Neurotransmitter changes, and, more recently 4. The role of "endogenous benzodiazepines. " This volume summarizes the results of a symposium held in Val David, Quebec from October 3D-November I, 1988, that was devoted to an evaluation of the evidence for and against the various hypothe- ses of HE. Data from studies in patients, in experimental (animal) models of HE, and in cultured cell preparations were discussed. In addition, a review of available approaches to the treatment and man- agement of HE was included. The therapeutic use of lactulose, anti- biotics, dietary treatment, and branched-chain amino acid treatments were included, as well as the results of preliminary studies of the therapeutic use of the benzodiazepine antagonist, flumazenil. Roger F. Butterworth, PhD Gilles Pomier Layrargues, MD v Acknowledgments The symposium was made possible by the generous financial assistance of: Hoffman-La Roche Ltd.

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.

After the great success of the fIrst issue of the series, the International Yearbook of Nephrology 1989, we were encouraged to proceed in our editorial venture to update nephrologists yearly, on all rapidly-changing areas of nephrology. Thus we have chosen new topics and appointed experts in the fIeld, asking them to give an objective review of the topic, up-dating the readers on the world-wide literature and providing them with a complete, accurate and up-to-date list of important, recent references. We have decided to maintain the successful format of the International Yearbook of Nephrology 1989. Thus each annual issue will be devided into sections; each section will have a different primary focus every year, depending upon what area is of greatest interest at the time. In other words, the Yearbook will remain different from the numerous books which appear every year covering all aspects of nephrology. In the Yearbooks you will fInd topics usually anavailable in nephrology textbooks. In this issue we have improved the printing quality of the book, with a more uniform format throughout the volume, despite the use of camera-ready manuscripts for direct photo-offset reproduction (a procedure mandatory for a rapid publication).

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

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.

Never before has such a history of the pancreas been presented. From antiquity until today, "rediscovery," translation and sequential presentation, in step with cultural changes in society, make this a unique contribution. Only from the perspective of the two octogenarian-authors could such a narrative have been produced. Discoveries resulting either from chance observation or careful scientific inquiry "come alive" as the authors present not only the people who made them but the setting in which they occurred.

Key Features:
*From the pre-Christian era of Asia Minor, to Greece, Rome, Europe and America, to the explosive progress in Japan, the dreams, near-misses and great discoveries have been traced to their sources.
*The great discoveries of the anatomists, WirsA1/4ng, Santorini, Oddi, Vater and their colleagues have been recreated from their original reports.
*Physiology is traced through the discovery of the digestive enzymes; the islets, by the Berlin student for whom they were named; the hormones, beginning with the dramatic discoveries of insulin, gastrin and their fascinating tumors.
*Diseases of the pancreas, particularly pancreatitis and cancer, but also congenital anomalies and trauma, are described from the era preceding the microscope to the dawn of the 21st Century.
*The explosive developments of imaging, diagnosis and pancreatic transplantation are presented, leading to the development of the challenging field of Pancreatology - its science and clinical practice.
*Finally the authors, having spent many years distilling the contribution of the giants of the past and present, present a thought provoking Chapter entitled "Lessons from Historyand their Application to the Future."

This book systematically summarizes the ideas and technologies used in urine proteome analysis. It argues that change is the core of biomarker definition since the body uses its homeostatic mechanisms to correct changes in the blood. This means that urine is probably a better source of biomarkers than blood. A roadmap to the urinary biomarker era is proposed, and researchers are reminded of the potential opportunities and risks in their study design. Kidney diseases are emphasized as they produce the most significant changes in urine. This book tries to show researchers and graduate students, who are in or entering the field, "all things considered" rather than "the current affair".

My thoughts about the Hemolytic Uremic Syndrome (HUS) got started in 1961 along with my attempt to return to Argentina. As I sought my way in Buenos Aires, I visited Carlos Gianantonio whom I had met in Caracas the year before during the Pan American pediatric meetings. At that time he was actively working on HUS which had become an epidemic in Buenos Aires and other parts of Argentina. I was impressed by the team effort and devotion of his group to such heavy demands. They obviously were meeting the challenge at an amazingly high level under a very crippling physical situation with shortages of space, laboratories and equipment. His group together with Dr. Becu, at the time the pathologist at the Children's Hospital of Buenos Aires (we had met through his mother who was instrumental in arranging my return to Buenos Aires), wrote some of the classic papers on HUS. Through the years as Dr. Gianantonio became more involved in general pediatrics, the administrative aspects and its orientation in Latin America, he became known for his deep philosophical questions as to what we are doing and where we are going. His questions have obvious implications regarding an agressive approach to our pediatric nephrology patients.

During the past decade, there has been a renaissance of interest in the use of peritoneal dialysis as a primary dialytic modality for the treatment of children with end stage renal disease (ESRD). The development of the technique of continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD) has markedly changed the approach to children requiring dialytic therapy. The availability of these techniques has facilitated prolonged dialysis in infants and has for the first time given pediatric nephro logists in many areas of the world an opportunity to consider dialysis in chil dren afflicted with ESRD. I have enlisted the collaboration of colleagues from Europe, South America, Canada, and the United States in compiling this multidisciplinary text, which hopefully contains the most up-to-date, comprehensive information regarding the use of CAPD/CCPD in children. It is my hope that every nephrologist (pediatric and adult); nephrology nurse (pediatric and adult); nephrology tech nician, or allied health professional dealing with children who require these therapeutic modalities will be able to resolve immediately any confounding clinical or technical issues that arise by using the information contained in this text. Demographic data on the use of CAPD/CCPD in children in Europe is provided from the EDTA Registry and in the United States from the National Peritoneal Dialysis Registry. The particular problems encountered in the use xiii xiv Preface of CAPD in children in developing countries is detailed by Dr. Grunberg and his colleagues in Uruguay."

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.

Vittorio E. Andreucci of keeping alive patients in terminal chronic Initially created with the purpose renal failure, dialysis has undergone improvements in methodology, and its final goal has become complete health rehabilitation and optimization of the quality of life of chronic dialysis patients. To achieve this, many investigators have attempted to increase dialysis efficiency and at the same time shorten dialysis time. Their main concern was, obviously, patient safety: the Latin proverb 'primum non nocere' is still valid all over the world. Thus, when clinical observations of the first patients on regular dialysis therapy suggested an inverse relationship between duration of dialysis sessions and severity of peripheral neuropathy, long and frequent dialysis sessions were considered the only way to prevent the catastrophic consequences of nerve damage and underdialysis syndrome. It was then, in 1971, when dialysis duration was 8- 12 hours per session, that Vincenzo Cambi started a 'short dialysis' trial, i. e. , 4 hours 3 times weekly or 3 hours every second day. For the first time, dialysis was shortened from 24-36 hours weekly to 10. 5-12 hours weekly [1, 2]. In 1971 I was still at the Parma University Hospital. We had both just returned from the United States, and Dr. Cambi was responsible for the dia lysis unit.

Cardiac disease is the major cause of death in dialysis patients, accounting for over one third of deaths. This book focuses on myocardial function and dysfunction in chronic uremia. It is aimed at practicing and training nephrologists, cardiologists, and internists, and at research workers in the field. We have tried to produce an up-to-date, in-depth review of the subject by inviting experts in clinical epidemiology, pathophysiology, and thera peutics to write the 18 chapters. The book is divided into three sections. The first section comprises five chapters that provide an overview of the burden of illness associated with cardiac disease in end-stage renal disease and a review of clinical epidemi ological aspects of various cardiac diseases that occur in renal patients. The second section discusses abnormalities of left ventricular contractility and mass, and the factors that predispose to both systolic and diastolic disorders. The importance of hypertension, anemia, hyperparathyroidism, hyper lipidemia, and diabetes mellitus in predisposing to these abnormalities is reviewed splendidly by researchers active in these areas. The final section concentrates on therapeutics. Data and opinion on management of congestive heart failure, cardiomyopathy, coronary artery disease, hypertension, and arrhythmias are provided. In editing this book, we have reviewed an extensive literature, but un fortunately we have become more aware that substantial gaps in our knowl edge exist. Insufficient high-quality clinical research has been undertaken xiii xiv Preface regarding the various cardiac diseases that occur in end-stage renal disease."

Neoplasias (tumors) are uncontrolled and progressive new growths of tissue. Frequently physicians caring for patients with neoplastic diseases are confronted with kidney or fluid and electrolyte complications that occur as a direct consequence of the neoplastic process or its treatments. The nine expert essays in this practical and clinically-oriented volume address the origins and treatment of most of these complications. Includes references to recent and classic studies.

"Rule IV. There is need of a method for finding out the truth. Rule V. Method consists entirely in the order and disposition of the objects toward which our mental vision must be directed if we would find out any truth. We shall comply with it exactly if we reduce involved and obscure propositions step be step to those that are s- pler, and then starting with the intuitive apprehension of all those that are absolutely simple, attempt to ascend to the knowledge of all others by precisely similar steps. " -Rene Descartes, Rules for the Direction of Mind ..".Perhaps he would sooner satisfy himself by resolving light into colours as far as may be done by Art, and then by examining the properties of those colours apart, and afterwards by trying the effects of reconjoyning two or more or all of those, and lastly by separating them again to examine what changes that reconjunction had wrought in them. This will prove a tedious and difficult task to do it as it ought to be done but I could not be satisfied till I had gone through it. " -From Newton's letter, quoted in The Life of Isaac Newton by Richard Westfall. Cambridge University Press, 1993.

Increasing the accumulation of aluminum in the bone (body) in cases of renal osteodystrophy may influence the histopathologic aspect of the bones. Alumi- num blunts the effect of increased PTH secretion and favours the genesis of osteoid. That means, in cases of renal failure combined with aluminum accumulation, a relatively low bone tunover is found and no fibrosis of the bone marrow. Furthermore the amount of osteoid is increased. This means that there is evidence of osteomalacia especially when the latter is defined as an increased amount of osteoid covered with a relatively low number of cubic osteoblasts. To a certain extent the effect of aluminum accumulation is comparable to the effect of PTX. Treatment with DFO may normalize the bone, although not necessarily with a concomittant disappearance of alumi- num from the bone. The presence of aluminum in the bone can be suggested by routine histologic investigation of the bone and can be made rather probably by the aluminum staining combined with iron-staining, but can only be proven by more advanced techniques like ET AAS and LAMMA. References 1. Boyce BF, Elder HY, Elliot HL, Fogelman I, Gell GS, lunor Bl, Beastall G, Boyle YT, 1982: Hypercaicaemic ostemalacia due to aluminium toxicity. Lancet 6: 1009. 2. Verbueken AH, Visser Wl, Van de Vyver FL, Van Grieken RE, De Broe ME, 1986: The use of laser microprobe mass analysis (LAMMA) to control the staining of aluminum by aurin tricarboxylate (aluminon). Stain Technology 61: 287.

For the last two decades, the topic of chronic renal failure has been dominated by discussions on dialysis and transplantation. As facilities for treating patients with end-stage renal failure have become more readily available, at least in Europe and North America, attention has once again been drawn to conservative measures which may improve both the overall prognosis and the quality of life of patients with renal impairment. Although severe renal failure may be progressive and many patients will ultimately require some form of renal replacement therapy, it is now widely appreciated that distressing symptoms can often be ameliorated by judicious medical treatment. Children as well as, and perhaps to a greater extent than, adults may benefit from such therapy. This volume examines relevant trends in the conservative man agement of both adults and children with chronic renal failure. Each chapter has been written by recognized experts and provides infor mation of clinical relevance for the average clinician. As the overall prognosis for patients with end-stage renal failure improves it is clear the management of patients with relatively stable chronic renal failure is an important topic not only for nephrologists but for all practising clinicians."