In all varieties of organ transplants, early results have dramatically improved over the past two decades and failures due to acute rejection are becoming rarer. Efficient immunosuppressive regimens have been developed with the objective of very good results at 1, 3 and 5 years. Successful transplants, however, are significantly less frequent at 10 and 20 years, and many patients require retransplantation. Many factors are involved in late graft loss and it is now well recognized that, in addition to chronic rejection, a number of non-immunologic factors play a prominent role. In the case of renal transplantation, a reduced mass loss (transplantation of a single kidney, sometimes from an aged donor, ischemic injury and alteration of some nephrons in the case of early acute rejection) will result in slowly progressing chronic renal failure, even in the absence of any supplementary attack of an immunological nature. The new treatments must be analyzed in the light of their capacity to reduce these late failures. Several preventive measures can also limit both immunologic and non-immunologic factors of late transplant deterioration.

Chronic renal disease has received increasing attention and concern since the passage in 1972 of PL 92-603, which provided coverage for end-stage renal disease (ESRD) treatment by the federal government. The human and economic costs of the ESRD program serve to emphasize the need to prevent or to arrest those diseases resulting in chronic renal failure, since none of the available treatments is without complications and/or side effects. The ESRD program, the only federal one that provides coverage for a catastrophic illness for almost the entire population (those qualifying under Social Security), cost almost $2 billion in 1983. The escalating costs of the ESRD program are attributed to the increasing number of patients requiring treatment and have focused concerns of the United States Government, both Congress and the administration, on ESRD. The National Institutes of Health (NIH), especially the Kidney, Urology, and Hematology Division of the National Institutes of Arthritis, Diabetes, and Digestive and Kidney Diseases (NIADDK), supports a sizable research program that bears on chronic renal disease and in association with this has sponsored many conferences and workshops on research on and causes and complications of chronic renal failure. This book is an outgrowth of the issues addressed by participants at a number of NIH conferences held in the 1980s.

Professor David Kerr Royal Victoria Infirmary) Newcastle upon Tyne Do we need another book on renal disease? There are few small books, particularly from this side of the Atlantic, which provide a really sound foundation of renal physiology, biochemistry and immunology. For two decades "The Kidney" by Hugh de Wardener has given a splendid background in renal physiology but I doubt if any author has brought to this subject as wide an experience and knowledge of basic science as Dr Wardle possesses. His researches have ranged over haematology, the role of in travascular coagulation in acute renal failure, the biochemistry of uremic metabolites, the immunology of glomerulonephritis, to hyperlipidemia in the genesis of arterial disease. In all these topics he has mastered the laboratory techniques as well as studying the patients personally. He therefore has a unique opportunity to show how renal disease can be illuminated by an understanding of the pathogenetic mechanism and to point the way to future treatment more logical than the crude and empirical methods we use today. This approach should appeal particularly to the young graduate whose memory of biocht: mistry and physiology is still reasonably fresh."

In June, 1981, we conducted a two day international symposium in Rome devoted to original scientific presentations on arachidonic acid metabolism in the kidney. Scientists from 20 countries were represented either in the general scientific program or in the poster presentation. This book does not represent the proceedings of this international gathering, but rather the edited manuscripts specifically prepared as sum- maries of the scientific presentations. We feel that the timeliness and originality of the contributions as well as the need for a compilation of existing work on prosta- glandins, thromboxane, and the kidney warrant this publication. The meetings would have been impossible without the generous and substantial support of the Italian government, the National Institutes of Health, United States Public Health Service, and Merck Sharp & Dohme International. Supplementary support was also received from Ciba Geigy S. p. A. , Ente Fiuggi, Farmitalia Carlo Erba S. p. A. , Glaxo Laboratori S. p. A. , Hoechst Italia S. p. A. , Leo Pharmaceutical Products, Pfizer Italiana S. p. A. , Sigm? Tau S. p. A. , Squibb S. p. A. , The Upjohn Company, Wellcome Italia S. p. A. , and Burroughs Wellcome Company. The efficient organization of the symposium was largely attributable to the superb efforts of Elisabeth Mutschlechner and Miki Scarinci of C. K. International, Rome. Linda Goldberg provided expert and invaluable editorial and secretarial assistance in the organization of this book. The book is divided into four major sections comprising: I.

It must be considered that there is nothing more difficult to carry out, nor more doubtful of success, nor more dangerous to handle, than to initiate a new order of things. Machiavelli: The Prince (1513) These are the Proceedings of a Conference on Temperature and Environmental Factors and the Testis which took place at New York University School of Medicine, December 8th and 9th, 1989. There is good reason to believe that this was the first of its kind to address, exclusively, the implications of temperature for this highly thermosensitive organ and its precious genetic cargo. The organizers of the Conference hoped to stimulate interest in this area which, paradoxically, has a considerable literature but which has received scant attention and sometimes outright opposition from clinicians expert in male infertility. There have been studies of the relationship of temperature to reproduction starting in the mid-18th Century with observations of the relationship of water temperature to spawning of fish. There is also a vast literature on the deleterious effects of externally applied heat upon spermatogenesis but little study of the possibility that intrinsic heat may be an important etiologic factor in subfertile semen. Today, fertility research has largely ignored this in favor of research in areas which have not produced successes, in terms of live births, comparable to what can be obtained by varicocelectomy (when appropriate) or scrotal hypothermia: viz. 1. Concentration upon the endocrine aspects of testicular function and its relation to spermatogenesis.

The cause of end-stage renal failure in one-third of patients treated by regular haemodialysis or kidney transplantation is some variety of glomerular disease. Less serious glomerular dis orders are more common and often cause inappropriate conster nation to the patients and, sometimes, to their doctors. Similar clinical features can be produced by pathological lesions ranging from the trivial to the life-threatening, and renal biopsy is often necessary to establish the diagnosis. However, its widespread use during the past 20 years has enabled clinicopathological correlations to be made and the natural history of many 'glomerulopathies' to be established, though large areas of uncer tainty remain. In contrast to symptomatic measures, such as the management of uraemia or the nephrottc syndrome, the use of treatment in arresting the progress of the glomerular lesion itself is controver sial and is based on anecdotal evidence rather than controlled trials. Knowledge of the renal pathology will, at least, enable conditions in which immunosuppressive therapy is appropriate to be distinguished from those which are benign or self-limiting. In this book symptomatic management of the clinical syn dromes is detailed, but classification is firmly based on renal histological appearances. The relevance of immunofluorescent microscopy, ultrathin section examination and electron micros copy to our understanding of pathogenesis is described, as well as the uses of these techniques for morphological discrimination."

When Shaul Massry and Herbert Fleisch asked me to write a foreword for this book, I was honored and eagerly looked forward to reading the many chapters. As they came and I skimmed through them, my mind wandered back to the earliest classic contributions in this field in the late 1920s and early 1930s by Albright and his associates, Greenwald and Gross and Adolph, on the homeostatic regulation of inorganic phosphate and the central role of parathyroid hormone (PTH) in this regulation. They clearly showed the exquisite sensitivity of the renal handling of phosphate to varying dietary and parenteral loads and to changes in the level ofPTH. That two outstanding investigators in the field of divalent ion me tabolism should choose to edit a book solely about the renal handling of inorganic phosphate shows how far we have progressed from these early classics to the recent almost exponential increase in the research and publications related to this subject. Despite this increase, I asked myself, is such a large new monograph, consisting of 13 chapters and 30 distin guished authors, warranted? My reading of these chapters and my learning so much from them convinced me that it is, and my pride was heightened in being asked to write the foreword for this book."

We are pleased to present to our readers the proceedings of th~ Third Bari Seminars in Nephrology. The tDpic ~f these proceedi~gs deals with effects of drugs and o:.yst el'll C ct i se;'Isc;- an the Id dney. Tho B?rj S~~jnar5 in Nephr~logy are bi-annual meetings ~tt~~~Dd k) D large international audience comprised of clinicians-scientist~ in the various displines of ~~phrnlDgy nnrl rQlated fi~ld$. The ne~t Bari S~mjnar5 of Nephrology will take place i" npril 19qn ~nd thp theme of the gathering will be Interstitial Nephritidies and Obstructive Uropathy. We are indc-bted for the goner-ells financial support of the Centro N::I~innalC' tiGBP:'llGBP'", Pichp.rche, Italy. Alberto Amerio Pasquale Coratelli Vito M. Campese Shaul G. Massry vii CONTENTS Lupus Nephritis: Pathogenesis, Course and Management .*..*...3 James E. Balow Prognostic Determinants in Lupus Nephritis ...*...* 17 P. Coratelli, R. Rizzi, G. Pannarale, A. Ramunni M. Giannattasio, and G. Passavanti Thrombotic Microangiopathy in Lupus Nephritis . * * . . 35 . M.T. Porri, M.I. Quarenghi, F. Ferrario G. Colasanti, R. Rossi, E. Schiaffino, G. Toia, and G. D'Amico Vasculitis and the Kidney . * ...* ...* * * 41 .

The management of chronic renal failure by dialysis and transplantation has now become an established form of treatment in many parts of the world. However, these forms of treatment have brought with them problems in relation to the selection of patients, economics, clinical problems such as hypertension, encephalopathy, anaemia and renal bone disease, and psychological and social problems. The management of haemodialysis has changed over the years with developments in dialysers, vascular access and the duration of dialysis. Although the overall survival from renal trans plantation has changed little in the past four or five years, there are hopes of improvements in relation to tissue typing and enhancement. Perhaps the most important aspect in the management of chronic renal failure is the multi-disciplinary approach. Nursing and medical staff work closely with dialysis technicians, engineers, dietitians, local authority per sonnel, social workers and with the relatives of the patients. The symposium was planned to draw together representatives from all disciplines involved in the care of patients with chronic renal failure. One of the most relevant sessions was that in which two patients with chronic renal failure described their experience."

The kidney, similar to the heart, plays a three-fold role in essential hypertension. First, it participates in the patho genesis of arterial hypertension. Second, it suffers as a target organ of long-standing hypertension, and third, it experiences the effects of antihypertensive therapy. Perhaps most contested at the present time is the involvement of the kidney in the patho genesis of essential hypertension. More than a century ago, William Osler put forward three basic hypotheses about the "genuine contracted kidney. "l 1. "The hypertrophy can be regarded as an effect to overcome a sort of stop-cock action of the vessels when under the influence of an irritating ingredient in the blood greatly contracted and increased the peripheral resistance. " Clearly this hypothesis of an "irritating ingredient" is perhaps the most convincing nowadays, and numerous attempts have been made to identify a specific vasoconstrictive agent in the blood in essential hypertension. 2. "The obliteration of a large number of capillary territories in the kidney materially raised the arterial pressure. An additional factor of dimin ished excretion of water also heightened the pressure within the blood vessel. " Today we know that fluid volume overload in the presence of reduced renal mass seems to be the most likely mechanism accoun ting for renal parenchymal hypertension and, as shown by Guyton's group, for certain forms of experimental hypertension. 3.

This volume emphasizes the comparative approach to under standing vertebrate renal function. I am convinced that this approach is of particular value in understanding both the details of renal function at the cellular and subcellular levels and the renal role in regulating fluid volumes and solute concentrations. My exposure to this approach first occurred during a student research experience in the laboratory of Wilbur H. Sawyer, who also provided an introduction to the works of Homer W. Smith and August Krogh. The importance of this approach was reinforced by doctoral and postdoctoral research in the laboratory of Bodil Schmidt-Nielsen. It has been confirmed through years of personal experience since then. My research and my understanding of renal function have been aided through the years by collaboration and discussion with numerous students and associates. Of particular impor tance in developing my views on comparative renal function, and especially on the relationship of structure to function, has been my long association with my colleague and friend, Eldon J. Braun. Donald S. Farner, who suggested the writing of this volume, provided valuable editorial assistance. Much of my personal research in this area has been supported over the years by grants from the United States National Science Foundation and National Institutes of Health. The writing of this volume was completed while I was in Wiirzburg, Federal Republic of Germany, supported by a Senior U.S. Scientist Award from the Alexander von Humboldt Foundation."

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."

Im Juni 1979 hatte in Dusseldorf ein Symposion uber Diuretika stattgefunden. Behandelt wurden experimentelle und klinische Ergebnisse mit Diuretika, unter anderem mit Diucomb. Ziel des Symposions war, Untersuchungsergebnisse zu referieren und diskutieren. Teilnehmer waren Wissenschaft ler aus der Schweiz, Osterreich, Grossbritannien, USA und der Bundesrepublik Deutschland. Das Material dieses Symposions wurde uberarbeitet, Diskussionen durch einen Redaktionsstab gestrafft. Wir danken Frau J. BOROS fur wertvolle technische Assistenz. Der Springer-Verlag hat uns wiederum sach kundig beraten und ist in grosszugiger Weise unseren Wunschen entgegengekommen Die Herausgeber Inhaltsverzeichnis Einleitung. F. KRUCK . . . . . . . . . . . . . 1 1. Wirkungsmechanismen. Moderation: K. GREEFF . 3 Plasma Concentrations and Comparative Bioavailability of Bemetizide and Triamterene in Combination. L. F. CHASSEAUD . . . . . . . . 5 Pharmakokinetik von Diuretika bei eingeschrankter Nierenfunktion. H. KNAUF und E. MUTSCHLER 14 Diskussion 24 Neue Daten zur Toxizitat von Diuretika. F. LEUSCHNER 26 Diskussion 29 2. Renale Wirkungen. Moderation: O. KRAuPP. . . . . . . . . . . . 33 Die Wirkungsweise diuretischer Substanzen in Abhangigkeit von ihrer re- len Behandlung. P. DEETJEN . . . . . . . . . . . . . . . . . . . 35 Effects of Diuretics on Renal Potassium and Hydrogen Ion Transport. G. GIEBISCH and M. HROPOT . . . . . . . . . . . . . . . . . . . 42 Wirkungen von Diuretika auf den transzellularen Elektrolyttransport der Niere. M. WIEDERHOLT und L. L. HANsEN 53 Diskussion 60 Interaktion zwischen Diuretika und renalem Prostaglandinsystem. H. J. KRAMER, B. STINNESBECK, W. PRIOR und R. DUSING 64 71 Diskussion Untersuchungen zum Wirkungsmechanismus von Acetazolamid und SITS auf den Bikarbonattransport im proximalen Tubulus der Rattenniere."

Nitrates have been for many years the cornerstone of cardiovascular therapy for various indications. Not only have nitrates stood the test of time for treatment of chronic stable angina pectoris, but the indications for them have markedly ex panded. They now include all forms of angina pectoris and myocardial ischemia, congestive heart failure and hypertensive emergencies. The beneficial effects of nitrates in all these conditions result from their vasodilatory properties, but it is still unclear whether the central or peripheral effects predominate in the thera peutic mechanism. Recently nitrates have been shown to fulfill the most important requirement for each and every drug - to reduce mortality. A large scale study revealed that isosorbide dinitrate, combined with hydralazine, reduced long-term mortality by 28% in patients with congestive heart failure. This finding will certainly stimulate research on nitrates, and it might be expected that interest in these drugs will markedly increase. The primarily used nitrates in clinical practice are nitroglycerin and the com plex organic nitrates, mainly isosorbide dinitrate. The organic mononitrates are now under clinical investigation, and isosorbide-5-mononitrate (IS-5-MN) appears to be especially promising.

Recent developments in recombinant DNA technology have led to the large-scale production of human erythropoietin and to the demonstration that it is effective in the treatment of renal and possibly some other anaemias. This has lent a new impetus to studies of the pathophysiology and pharmacology of the hormone which is reflected in this report of the proceedings of a meeting held in Liibeck in June 1988. In 15 papers, all from European centres, the broad topics covered are erythropoietin's physiology and chemistry, the patho- physiology of erythropoiesis and the use of erythropoietin in the treatment of anaemia. Several of the papers include up-to-date reviews of the literature. The field is now expanding rapidly, and this volume, though not comprehensive, usefully points up many areas of recent understanding as well as others of continuing un- certainty. Overall, it contains material likely to be of interest to biochemists and experimental haematologists as well as to phar- macologists, clinical haematologists and nephrologists.

In one golden age of medicine epitomized by William Osler, the physician also aspired to mastery of gross and microscopic pathologic anatomy. Now another such age has dawned in which ultrastructure and immunopathology provide insights into mysterious diseases of the kidney, connective tissues, joints, and muscles, among other sites. Dr. Anil K. MandaI has a background in clinical nephrology, experimental pathology, and diagnostic pathology of renal diseases that suits him well for his chosen task. This is to explain clearly the clinicopathologic entities seen by nephrologists, using the full range of available morphologic techniques. His ap- proach is brisk and incisive. To read his monograph as a pathologist is to make oneself a better clinician, and as a physician is to improve one's grasp of pa- thology. Such correlative knowledge seems at present the means most likely to lead to the ultimate control of some crippling chronic renal diseases. Sheldon C. Sommers, M.D.

The Department of Continuing Education of Harvard Medical School and members of the faculty of Harvard Medical School held a multidisciplinary course on the management of patients with urologic cancer in the fall of 1982. This course high lighted the multidisciplinary approach to the care of these patients, and outlined the clinical and pathophysiological basis for diagnosis and treatment. The term multidisciplinary was essential to the course in which the disciplines of uro logic surgery, medical oncology, and radiation therapy were each appropriately emphasized. Widespread interest in the contents of this course, and the timely and useful nature of much of the information presented there, has encouraged us to publish, in as rapid a manner as possible, new information and highlights of that course. A camera-ready format was used to allow rapid production, and a variety of disparate styles were maintained from chapter to chapter--some in prose, others in outline. Again, our intent was to disseminate information rapidly and accurately, and to that end, we felt that consistency of style was irrelevant."

Congenital adrenal hyperplasia (CAH) consists of a group of disorders of adrenal steroidogenesis. Each disorder results from an inherited deficiency of one of the several enzymes necessary for normal steroid synthesis. The different enzyme deficiencies produce characteristic patterns of hormonal abnormalities; the clinical symptoms of the different forms of CAH depend on the particular hormones that are deficient or that are produced in excess. The earliest documented description of CAH was by DeCrecchio in 1865 (DeCrecchio 1865). This Neapolitan anatomist described a cadaver having a penis with first degree hypospadias but no externally palpable gonads. Dis- section revealed a vagina, uterus, fallopian tubes, ovaries, and markedly enlarged adrenals. It is interesting that the subject suffered a confusion of sex assignment, being declared a female at birth and a male 4 years later. He conducted himself as a male sexually and socially. Since the original descrip- tion of this case, investigators have unravelled the pathophysiology of the inborn errors of steroidogenesis. 1 Steroidogenesis and Enzymatic Conversions of Adrenal Steroid Hormones A. Steroidogenesis The adrenal synthesizes three main classes of hormones: mineralocorticoids (17-deoxy pathway), glucocorticoids (17-hydroxy pathway), and sex steroids.

Advanced Renal Cell Carcinoma (RCC) cannot be cured by surgery alone. Its resillience to irradiation and chemotherapy demands a new approach to the management of this disease. This book provides an overview of the scientific and clinical developments of RCC, and clarifies the fields ofimmunotherapy and immunobiology. The book contains a compilation of approaches that will enhance the effectiveness of the management of advancedRCC, even in the absence of definitive pre-clinical data. These require additional study and will stimulate the reassessment of preliminary results.Furthermore, preliminary results of already implemented clinical trials withbiological modifiers are presented. Of special interest are the current achievements in the field of immunotherapy using topically and subcutaneously low dosage combinations of cytokines. This concise volume will benefit those seeking a thorough review of the research and the clinical aspects of RCC simultaneously.

Organ Shortage: The Solutions 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. "

The human prostate gland is of undoubted importance in reproductive physiology and is one of the commonest causes of clinical urological problems in the male patient. Despite the wealth of published lit erature relating to the prostate gland surprisingly little is understood about its neural innervation, the influence of pharmacological factors and its precise physiological functions. Indeed, benign disorders of the prostate gland including benign prostatic hyperplasia, bladder neck dyssynergia and inflammatory disorders of the prostate (prostatitis, prostatodynia) although well recognised clinically, are as yet poorly characterised and understood. It was not until the late 1960s that the subject of urodynamics, which for the first time allowed scientific assessment of the function of the lower urinary tract, was introduced. The first section of this book considers recent advances in our understanding of the innervation of the bladder and prostate gland and the changes in bladder function which accompany prostate medi ated bladder outflow obstruction. The clinical consequence of benign prostatic hyperplasia in many patients is bladder outflow obstruction and although the traditional treatment of these conditions is by the use of ablative surgery, in recent years a number of new modalities have been investigated and are reviewed in the second section of the book.

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."

The action of diuretics including cellular mechanisms of action, pharmacokinetics, and clinical usage, with much emphasis placed on the most recent findings on the pharmacodynamics of the respective drugs. During the past twenty-five years since volume 14 on Diuretica was published in the Handbook series, the cellular mechanisms of action of diuretics have slowly been unravelled. Today, the role of action within the target cells is known for most of the substances discussed. This has provided a new basis not only for the understanding of drug action but also for secondary effects and interactions. The book represents a comprehensive reference work on the diverse groups of diuretics which are among the most frequently prescribed medications.

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

Nephrology, initially born as a small branch of medicine, has, in the last few decades, become an extraordinary large field of medicine. The recent development of renal medicine is mirrored by the numerous nephrological journals published, a natural consequence of the increasing number of basic and clinical research studies performed continuously all over the world. Undoubtedly the progress which has occurred in the different, specific fields of renal medicine has given rise to subspecialities which range from renal physiology and pathology to hemo- and peritoneal dialysis and renal transplantation. Even the diagnostic methodology in nephrology, very useful in the clinical practice, has become a speciality within the speciality. Thus, the problem for clinical nephrologists, as well as for internists, is to remain continuously up-dated in all fields of nephrology. Nephrology textbooks are published continuously and in great number. However, the time required for having authors appointed, chapters completed, manuscript edited, galley proofs corrected and the whole book printed makes many textbooks already out of date when they go on sale and their half lives are very short. On the other hand, nephrological journals are so many and the articles so numerous and detailed, that it is often impossible to rely on them for up-dating practicing clinicians.