Biologics have revolutionised the treatment of many severe conditions, delivering exceptional clinical results but also producing exceptionally high prices. As patents expire, copies and price competition are expected throughout the world. However, due to the intrinsic heterogeneity and molecular complexity of biologic medicinal products, their copies cannot simply be authorized under the "generic rule" valid for small chemical entities. In response, a dedicated regulation was issued in the European Union. It is based on the concept of "biological medicinal products similar to a biological reference product", or "biosimilars". This book analyses the context of biotechnological production and addresses the European legal framework for biosimilar market approval. It highlights post-market authorisation issues, such as Risk Management Plans and substitution of products, and outlines some other issues, such as cost management and international nomenclature. This book is primarily intended for hospital-based physicians and pharmacists. It will also be a valuable resource for all actors from all countries who want to better understand the emergence of these new medicinal products within the European context.

While patients with metastatic renal cell carcinoma (mRCC) are now living longer with improved quality of life, the success of novel therapies for mRCC has created challenges for practicing oncologists. Many patients who initially respond to targeted therapies ultimately develop progressive disease due to acquired resistance to these agents. Additionally, some patients do not respond at all to any of the currently approved targeted agents, underscoring the need for continued and concerted efforts to identify other relevant targets and pursue alternative therapeutic strategies. Part of the Oxford American Oncology Library, Renal Cell Carcinoma is a concise handbook that addresses the complex management of patients with mRCC. The book begins with a review of the epidemiology, pathology, and biology of renal cell carcinoma followed by chapters on specific targeted therapies and managing complications. The final chapters discuss supportive and integrative care and emerging therapies.

Nocturia: Causes, Consequences and Clinical Approaches is the first volume exclusively on the topic of nocturia and is designed to be a comprehensive treatise on the subject. The volume is organized into 11 chapters first introducing and defining nocturia and its impact to patients and society, followed by chapters dealing with predictors and risk factors; relationship to sleep disorders; overactive bladder; and water homeostasis. Therapeutic areas addressing nocturia are covered in specific chapters and include pharmacotherapy affecting the bladder, prostate and kidneys as well as behavioral therapy and surgical intervention. Separate chapters are devoted to alternative therapies as well as the impact of nocturia in the elderly. The volume closes with a chapter presenting avenues for future investigation into the etiology and management of nocturia. Clinical case scenarios inclusive of figures and tables illuminate the evaluation and management of patients with nocturia. Nocturia: Causes, Consequences and Clinical Approaches will give physicians and related healthcare providers the background to understand the conditions causing nocturia, how nocturia affects society and the basis for its rational treatment. It will be used as a state of the art reference by urologists, urogynecologists, internists, nephrologists, pulmonologists, endocrinologists and sleep medicine specialists.

This second edition of the Manual of Clinical Dialysis is a concise and well-illustrated guide to all aspects of dialysis. All chapters have been revised and present a complete overview of the techniques, processes and equipment involved in clinical dialysis as well as an overview of the complications of dialysis. The manual also provides an overview of common clinical problems related to renal failure such as hypertension, anemia and renal osteodystrophy.

Pocket Reference to Renal Anemia, Second edition, provides a comprehensive overview of anemia in patients with renal disease, including the definition and causes of renal anemia, current management approaches, and the latest clinical practice guidelines. Key learning points are highlighted throughout the book and also listed at the end of the book for a quick reference. The book is useful for general physicians, fellows, and other healthcare professionals wishing to learn more about renal anemia.

"Endourology" provides a summary of the different endourological modalitites, especially the more advanced and controversial techniques, such as the antegrade resection of urethral valves, the transperineal I 125 seed implanations, the spoonloop resectoscope, flexible endoscopy, teflon injection to correct vesicoureteral reflux, stone manipulation in calyceal diverticula, as well as the extraperitoneal pelvioscopy. These techniques are supported by descriptions of the standard endourological procedures.

III. International Symposium on Peritoneal Dialysis

In 1986, the Committee of Experts on Blood Transfusion and Immunohae- tology of the Council of Europe chose for their Programme of Co-ordinated Research "An investigation of the procurement and sharing of transplantable organs for potential recipients who are highly sensitized to HLA-antigens." This topic was of common concern to all centres practising renal transplan- tion. The terms of reference of the study were: To estimate the number of patients who are virtually "untransplantable" because of high sensitization in each European country. To study the nature of immunization in terms of the type and specificity of antibodies present in the blood and techniques used for their detection. To investigate possible practical solutions - both current and future, invo- ing cross-matching procedures, the circulation of reference material from patients, and the willingness of the national organizations to share resources. 4. To explore other methods of resolving this problem. Although the study did not offer the prospect of a brilliant new insight into the problem of high sensitization, it was unique in several ways: for the first time we saw all European organizations collaborating in a common project to provide information on their activities, their problems and the methods to resolve them; it introduced, for this subject, relatively novel statistical methods to investigate susceptibility to sensitization and factors affecting transplant outcome; it enabled a large database of transplanted highly sensitized patients and matched controls to be assembled, that would have been unavailable as a research resource at any single centre.

Rejection and Tolerance is the latest subject in the Continuing Education series, organized by Fondation Marcel Merieux and Universite Claude Bernard in Lyon. The annual subject is chosen to reflect the status of the topical issues of the year, as taught by leading international experts. The contribution of transplantation and clinical immunology to advanced medicine is considerable and promising. The annual volumes in this series keep the reader abreast of these developments. "

Chronic Kidney Disease (CKD) is a recognized risk factor for cardiovascular events and death. The coexistence of CKD and heart failure is increasing in prevalence worldwide and requires a unique and subtle approach to patient management. The Kidney in Heart Failure focuses on the changes that occur in kidney physiology as a function of a failing heart. This comprehensive resource covers epidemiology, pathophysiology, management of kidney disorders and advances in nephropathy management. In addition, the latest therapies, common heart failure dilemmas and kidney disease markers are included. Each chapter is co-authored by a Nephrologist and Cardiologist, offering a unified perspective to these chronic conditions. This indispensible volume provides the reader with the depth-of-knowledge needed for assessing and treating the cardio renal patient.

We present to our readers the proceedings of the Second International Workshop on Phosphate. A short account of the history of the effort led to the Phosphate Workshops is appro priate and can be of interest to the reader. The idea for Phosphate Workshops was born in the early days of November, 1974. One of us (S. G. M. ) suggested the thought to a group of scientists gathered for a luncheon in one of the attrac tive small restaurants in Weisbaden, Germany. The purpose of the workshop was to bring together interested scientists to discuss the newer developments and the recent advances in the field of phosphate metabolism and the other related minerals. An Organizing Committee made of Shaul G. Massry (USA), Louis V. Avioli (USA), Philippe Bordier (France), Herbert Fleisch (Switzerland), and Eduardo Slatopolsky (USA) was formed. The First Workshop was held in Paris during June 5-6, 1975 and was hosted by Dr. Philippe Bordier. Its proceeding was already published. The Second Workshop took place in Heidelberg during June 28-30, 1976 and was hosted by Dr. Eberhard Ritz. Both of these workshops were extremely successful scientific endeavors, and the need for them was demonstrated by the great interest they generated among the scientific community. The Or ganizing Committee, therefore, decided to continue with the tradi tion to hold additional Workshops annually or every other year."

WEGENER'S GRANULOMATOSIS & ANCA-ASSOCIATED DISEASES: THE STORY CONTINUES The disease now designated as Wegener's granulomatosis (WG) was first described in 1931 by Heinz Klinger, who considered it to be a special form of polyarteritis nodosa. Klinger's friend, Friedrich Wegener, expanded on the first observations and interpreted the pathological and clinical fmdings to represent a distinct disease entity (Wegener, 1939). He described this entity as a "peculiar rhinogenous granulomatosis with a unique participation of the arterial system and the kidneys". Later, Godman and Churg (1954) established the classical diagnostic criteria (the "WG triad"): granuloma, vasculitis, and glomerulonephritis. In 1958 Walton pointed out the poor prognosis of WG based on a small number of published cases (mean survival time: 5 months). In 1966 Carrington and Liebow reported "limited forms" of WG with a defmitely more favorable prognosis. Since then positive results have been reported with cyclophosphamide therapy. In addition, a retrospective study of combined low-dose cyclophosphamide and prednisolone in 85 WG patients over a period of 21 years found a similarly encouraging outcome. The*latter experience led to the current "standard" treatment protocol (FAUCI et al. , 1973 and 1983). More recently, strong evidence has emerged that some of the morbidity and mortality ofWG - and other types of systemic vasculitis - may be a consequence of this treatment (Hoffman et al. , 1992).

This volume was designed as a text for medical students, house officers, and even clinicians. It deals with the most common problems in nephrology, providing new insight into how to improve clinical skills. A comprehensive overview of renal physiology and electrolyte disorders lays the groundwork for a clear presentation of the pathophysiological principles that underlie these disorders and a step-by-step presentation of the mechanisms behind the signs and symptoms of kidney failure. The origins of this book can be traced to the teaching of a Renal Pathophysiology course at the Washington University School of Medicine, beginning in the mid-1960s. When changes in the medical school curriculum took place in the early 1970s, an effort was made to synthesize the minimum core curriculum for sophomore medical students, and the distillation of "essential material" to be covered in the area of renal pathophysiology led to the development of the first edition of a renal syllabus. This syllabus has been used in our department since 1974, and, following some of the recommendations and critiques of students and faculty, it has been entirely reworked many times to improve its effectiveness and value. This book is a direct extension of that syllabus, integrated with contri butions from faculty members in our Renal Division, and expanded to include a section on therapy in most chapters. It is our hope that this format will serve the needs of not only sophomore and senior medical students, but also house officers, nephrology fellows, and clinicians."

Diabetic nephropathy is a tragic illness. Its often insidious onset in the insulin dependent (type I) diabetic, typically a young adult, heralds the last act in the course of a disease that will increasingly become the dominant preoccupation in the patient's shortened life. For most type II diabetics, the beginning of clinical renal insufficiency is but a phase in a continuous deterioration that affects the integrity ofjob, marriage, and family. The nephropathic diabetic is hypertensive, has worsening retinopathy, and more often than not, is also plagued by peripheral vascular insufficiency, heart disease, gastrointestinal malfunction, and deepening depression. Until the 1980's, few type I diabetics who became uremic (because ofdiabetic nephropathy) lived for more than two years. Hardly any attained true rehabilitation. This dismal prognosis is changing substantially for the better. Research in diabetes has resulted in striking advances at both ends of the type I diabetic's natural history. In one exciting clinical trial now underway in London, Ontario, halfofchildhood diabetics treated with cyclosporine within six weeks of onset evince"permanent" disappearanceofhyperglycemia and the need for insulin. At the otherendofthe natural historyofdiabetes for the nephropathic patientwith worsening eye disease (renal-retinal syndrome), who receives a kidney transplant, patient and graft survival, two years after cadaveric kidney transplantation in type I diabetics is now equal to that of the nondiabetic."

Proceedings of the FEMS Symposium on Genes and Proteins Underlying Microbial Urinary Tract Virulence: Basic Aspects and Applications, held September 16-19, 1999, in Pecs, Hungary. Urinary tract infections are among the most frequent diseases caused by microbial pathogens. In this volume, researchers, clinical microbiologists and clinicians exchange the latest ideas covering four major aspects of this important topic: * Genetic information, synthesis and assembly of virulence factors in urinary pathogens; * Regulation of genes involved in the phenotypic appearance of virulence; * Host-parasite interactions determining the process and outcome of the infection; * Possible applications of the above aspects in diagnosis, therapy and prevention.

Extracorporeal shock wave lithotripsy (ESWL)" arrived in the United States in February of 1984 with explosive impact in the field of urology. The first ESWL treatment in the United States with the Dornier H~ device occurred at the Methodist Hospital of Indiana, and by the end of 1984, In spite of the rapidly the United StatesESWL study group had accrued over2,5()() ESWL treatments. accumulated experience at the six institutions involved in the FDA trial of the Dornier HM] device, other urologists in this country and around the world had little opportunity to gain knowledge about the utilization of this revolutionary technique. For this reason, the Methodist Hospital of Indiana organized the first symposium on shock wave lithotripsy in February of1985. Interest in this meeting was intense, as approval of the Dornier device had occurred only a few weeks earlier in December of 1984. Because of the success of this initial meeting, subsequent meetings have been held annually in Indianapolis. Following the third annual symposium on extracorporeal shock wave lithotripsy in March of 1987, a number of participants and attendees requested that the information presented at the meeting be made available. Therefore, plans were made to publish the proceedings of the next meeting which occurred March 5 and 6, 1988. The Methodist Hospi tal ofIndiana' s 4th Symposium on Shock Wave Lithotripsy: State of the Art was the best attended meeting to date with over 650 registrants from 36 states and 24 countries.

The purpose of this volume and Pediatric Nephrology Seminar IX from which it was created is to provide easy access to current concepts in the diagnosis and management of kidney diseases in the newborn. Complimentary to this purpose is the opportunity the Seminar structure gives me to invite those particularly interested in the subject chosen to come together, share experiences and ideas in an unhurried, unpressured atmosphere for four con tinuous days - an oasis for me and, I am told, also for the faculty and registrants. This year's subject choice is an expression of my perennial interest in the kidney of the newborn. A step back to view the steps forward reveals unwittingly intertwined associations and actions which now fall into focus. When I was just beginning my pediatric nephrology training with Sol Kaplan at Downstate in Brooklyn, we discussed Bob Usher's pioneering thought that there was something wrong with the kidneys of babies with RDS. Without really knowing what needed to be done, I started looking at the kidneys of those babies. Subsequently, Dick Day who was Chairman of the Department of Pedia trics there, stopped me in the hall, and asked me to come into his office. Glowing in quiet introspection, he extolled the joy of working with one's hands, then hurried away to his laboratory. He had been the Director of the Newborn Nursery at Babies Hospital before coming to Downstate, and (as I later found out) was trying to do something with oxygen electrodes."

The sum of clinical problems caused by diabetic renal disease has been steadily increasing since the first edition of this book was published in 1988. The years since have seen tremendous progress in research activities. Importantly, this also includes improvement in the treatment programs to prevent end-stage renal failure. It has become clear that the diabetic kidney is extremely pressure-sensitive, responding to effective antihypertensive treatment by retarded progression of disease. Some agents may be more beneficial in this respect than others, although effective blood pressure reduction per se is crucial throughout the stages of diabetic renal disease. However, the prime cause of diabetic renal disease is related to poor metabolic control and it is now documented beyond doubt that good metabolic control is able to postpone or perhaps even prevent the development of renal disease. However, in many individuals we are not able to provide such a quality of control that will prevent complications, and therefore non-glycaemic intervention remains important.Maybe in the future non-glycaemic intervention will become the most important research area in diabetic nephropathy. Much information is now available on the exact mechanisms behind poor metabolic control and development of renal disease. It is likely that a combination of genetic predisposition and metabolic and haemodynamic abnormalities explain the progression to renal disease, seen in about 30% of diabetic individuals. Much of this development probably relates to modifiable genetic factors, such as blood pressure elevation or haemodynamic aberrations. However, mechanisms related to the response to hyperglycaemia are also of clear importance, as is the possibility that these metabolic or haemodynamic pathways may be inhibited. This volume reviews older data as well as the progress seen within the research on diabetic nephropathy over the last five years and describes the state of the art of the development.

The first sporadic observations describing renal abnormalities in diabetes were published late in the 19th century, but systematic studies of the kidney in diabetes started only half a century ago after the paper by Cambier in 1934 and the much more famous study by Kimmelstiel and Wilson in 1936. These authors described two distinct features of renal involvement in diabetes: early hyperfiltration and late nephropathy. Diabetic nephropathy is, despite half a century of studies, still a very pertinent problem, renal disease in diabetes now being a very common cause of end-stage renal failure in Europe and North America and probably throughout the world. It is a very important part of the generalized vascular disease found in long-term diabetes as described by Knud Lundbaek in his mono graph Long-term Diabetes in 1953, published by Munks gaard, Copenhagen. Surprisingly, there has not been a comprehensive volume describing all aspects of renal involvement in diabetes, and the time is now ripe for such a volume summarizing the very considerable research activity within this field during the last decade and especially during the last few years. This book attempts to cover practically all aspects of renal involvement in diabetes. It is written by colleagues who are themselves active in the many fields of medical research covered in this volume: epidemiology, physiology and pathophysiology, laboratory methodology, and renal pathology. New studies deal with the dia gnosis and treatment of both incipient and overt nephropathy by metabolie, antihypertensive, and dietary invention."

We have witnessed a rapid development within the field of the kidney and hypertension in diabetes mellitus. A significant amount of work within the traditional areas has been published, and several new dimensions are now being developed, mostly in the experimental setting. These dimensions are discussed in several chapters of this new edition, The Kidney and Hypertension in Diabetes Mellitus, Fourth Edition. This volume endeavors to cover all aspects of renal involvement in diabetes. It is written by colleagues who are themselves active in the many fields of medical research covered in this volume: epidemiology, physiology and pathophysiology, laboratory methodology and renal pathology.

There is a rapid increase in interest related to novel approaches in artificial kidneys, artificial liver, and detoxifi cation. Recent research has included the successful clinical appli cations of the principle of artificial cells for adsorbent hemo perfusion. Since it is 20 years ago at McGill that the first report on "Artificial Cells" was presented, I thought it might be useful to get together a small group of speakers and participants for a day before the ASAIO meeting to discuss some recent advances in the area of the clinical applications of artificial kidney, artificial liver and artificial cells with emphasis on adsorbent hemoperfusion. However, the enthusiastic supports of distinguished speakers, session chairmen and participants were such that the original pro jection of 100 participants had expanded to a preregistration total of 250, from Australia, Canada, England, France, Germany, Israel, Italy, Japan, The Netherlands, Scotland, Sweden and U. S. A. The program also expanded to include a review section on hemodialysis, dialysate regeneration, hemofiltration, resin hemoperfusion and oxystarch given by their respective originators. The remaining of the symposium emphasizes the status of the art on different encap sulated adsorbent hemoperfusion approaches. I would like to apolo gize to those who we could not accommodate beca se of space limita tions. It is hoped that this symposium volume may be useful for them and for others who are interested in this area. Special thanks are due to Ms Joanne Toms for her excellent secretarial assistance for the conference and Mrs."

Renal sonography forms a basic part of routine diagnostic strategy. This textbook summarizes eighteen years of experience in diagnostic ultrasound. We want it to serve as a guide to both imagers and mere consumers of information. That is why we shall emphasize practical advice and diagnostic pitfalls; it is also why we shall often deal with the relations of sonography with other diagnostic procedures, which it may complement or replace, precede or follow, the purpose being to achieve efficiency at low cost. We shall limit our subject matter to the kidney itself and the neighboring retroperitoneal compartments, dealing only briefly with the lower urinary tract, which requires specialized procedures. We devoted considerable space to renal sonography in our book Clinical Atlas of Ultrasonic Radiography, published in 1973. Since then, nothing has changed and everything has changed. Nothing, because even then the differential diagnosis between a solid and a cystic mass, the etiologic diagnosis of a nonsecreting kidney, and the positive diagnosis of a traumatic juxtarenal hematoma were quite reliable, making possible drastic reductions in the indications for instrumental roentgenologic examinations. Everything, be cause improved resolution and grey scale imaging (already partially achieved in 1973, thanks to real time) have profoundly refined both anatomic and pathologic ultrasonic studies. And now high resolution real time imaging has revolutionized renal examination techniques, whereas Doppler is entering routine ultrasonic diagnosis."

It is increasingly recognized that various transporter proteins are expressed throughout the body and determine absorption, tissue distribution, biliary and renal elimination of endogenous compounds and drugs and drug effects. This book will give an overview on the transporter families which are most important for drug therapy. Most chapters will focus on one transporter family highlighting tissue expression, substrates, inhibitors, knock-out mouse models and clinical studies.

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."