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Uremia is a chemical, toxic, potentially fatal condition. In a variable pattern, uremia ultimately kills almost every cell in the body. Uremia is produced by hundreds of diseases, both kidney and systemic (e.g., diabetes). These kinds of uremic conditions range from the acute and catastrophic to the slowly and moderately progressive. Humans and medicine have struggled at least since Hippocrates to understand, prevent and treat uremia and thereby prolong the useful lives of the young and the aging. Accelerated by the spectacle of premature uremic deaths from crush syndrome, shock, and forms of nephritis during major wars and disasters, medicine fused clinical and basic science with industrial technology and came up with two effective treatments. Dialysis in several modes and kidney transplantation became feasible but proved complex and expensive. How people, struggling to survive, were able to use a representative form of government to treat all kidney patients, forms a human story: A "people" story. Since it culminated within a single medical generation, it is possible to tell the story as a participant and eye-witness. This is how the medical, social and national organization of substitution therapy for uremia evolved. Since it is legislatively called end-stage renal disease, we titled the entitlement, "How ESRD-Medicare Developed."

In this article I reflect on events between 1968 and 1972 that influenced the enactment of the End-Stage Renal Disease (ESRD) Amendment to Public Law 92-603.

Historians have suggested that US president Andrew Jackson (1767-1845) experienced lead and mercury poisoning following his therapeutic use of calomel (mercurous chloride) and sugar of lead (lead acetate). To evaluate these claims, we performed direct physical measurement of 2 samples of Jackson's hair (1 from 1815, 1 from 1839). Following pretreatment and acid digestion, mercury was measured using cold vapor generation techniques, while lead levels were measured by electrothermal atomic absorption spectrophotometry. Mercury levels of 6.0 and 5.6 ppm were obtained from the 1815 and 1839 hair specimens, respectively. Lead levels were significantly elevated in both the 1815 sample (mean lead level, 130.5 ppm) and the 1839 sample (mean lead level, 44 ppm). These results suggest that Jackson had mercury and lead exposure, the latter compatible with symptomatic plumbism in the 1815 sample. However, Jackson's death was probably not due to heavy metal poisoning.

Over the last 50 years nephrology has seen milestone achievements in basic sciences as well as in clinical medicine. This article describes the start of clinical nephrology in Austria in the 1950's and the significant changes over the last decades. With 625 patients/pmp Austria has worldwide one of the highest numbers of patients treated for endstage renal disease. In 1995, 5020 patients were alive on replacement therapy, equally distributed between transplanted and dialyzed patients. An overview over the developments that led to Austria's prominent role in the treatment of end stage renal disease is given.

Although hemodialysis began in the early 1960s, it did not begin to really grow until 1973, when the Federal government started to pay for end-stage renal disease (ESRD) treatment under Medicare. Since then, the Health Care Financing Administration (HCFA) has made a series of mistakes while maintaining this very successful program. This article traces the steps HCFA took, and the responses by the providers that produced the situation we have today. This program pays the lowest amount for hemodialysis of any industrialized nation, and most likely as a result has the highest mortality rate (23%) of any of the same countries. The problem as outlined is that HCFA attempted to ration by price while ignoring quality. This has been compounded by the providers finding more and more ways to reduce cost to continue to make a profit while not improving quality. The result is a program that could have been much better, and a patient population that has suffered.

Progress in the development of permanent vascular access for hemodialysis has been much slower than progress in other areas of end-stage renal disease (ESRD) patient care. This article provides a brief historical overview of the major means used for vascular access since the start of chronic hemodialysis. These access modalities include external shunts, arteriovenous fistulae, prosthetic arteriovenous grafts, needle-less access devices, and tunneled central venous catheters. Despite the evolution of access methodology, vascular access complications remain a major impediment to the full rehabilitation of the chronic hemodialysis patient.

Mozart, perhaps one of the greatest geniuses of modern age, died mysteriously at the age of 35 in Vienna in 1791. The causes of his death are still somewhat obscure and debated since we do not have any documentation acceptable by current scientific standards. Inevitably, the conclusions reached are highly debatable. In the present article the various interpretations of Mozart's death are taken into consideration-from his possible poisoning to causes of death more acceptable by the present diagnostic criteria. We suggest that the terminal cause of death was brain hemorrhaging or stroke, complicated by broncopneumonia and associated with renal failure induced by proliferative glomerulonephritis and glomerulosclerosis.

Uremia is a chemical, toxic, potentially fatal condition. In a variable pattern, uremia ultimately kills almost every cell in the body. Uremia is produced by hundreds of diseases, both kidney and systemic (e.g., diabetes). These kinds of uremic conditions range from the acute and catastrophic to the slowly and moderately progressive. Humans and medicine have struggled at least since Hippocrates to understand, prevent and treat uremia and thereby prolong the useful lives of the young and the aging. Accelerated by the spectacle of premature uremic deaths from crush syndrome, shock, and forms of nephritis during major wars and disasters, medicine fused clinical and basic science with industrial technology and came up with two effective treatments. Dialysis in several modes and kidney transplantation became feasible but proved complex and expensive. How people, struggling to survive, were able to use a representative form of government to treat all kidney patients, forms a human story: A "people" story. Since it culminated within a single medical generation, it is possible to tell the story as a participant and eye-witness. This is how the medical, social and national organization of substitution therapy for uremia evolved. Since it is legislatively called end-stage renal disease, we titled the entitlement, "How ESRD-Medicare Developed."

From the beginning of the first described hemodialysis in 1889, history has shown an exponential evolvement of systems that have resulted in greater safety, efficiency, and broader utilization. It took 60 years, 1947, for the technology to be used in a clinical setting in North America, treating acute renal failure. Commercial interests became involved in the mid 1950s, resulting in the "twin coil" dialyzer, costing five times the current cost of similar membranes. The entry of commercial entities created a rapidly escalating technology in dialysis delivery systems to be used in the chronic recurring dialytic procedure: blood pumps, pressure monitors, needles, dialysate delivery, ultrafiltrate control, membrane design and configuration, dialysate composition. All of these have, for the most part, required trained staff and increasingly comfortable facilities to accommodate the rather static thrice-weekly hemodialysis procedure. The future will likely see more home dialysis, more frequent dialysis, better on-line monitoring, with attention to those factors which have allowed the greatest cause of morbidity, cardiovascular disease, to be controlled.

Renal transplantation has become the treatment of choice for most types of end-stage renal failure. Immunosuppressive drug therapy has improved enormously over the past 25 years, and the advent of potent new drugs in addition to cyclosporine make multiple drug therapy for immunosuppression the direction of the immediate future. Monoclonal antibodies have so far had a limited role in immunosuppression, but are likely to prove of value in protocols aimed at inducing specific unresponsiveness to a renal allograft. This remains the goal of transplantation biology, because the long-term complications of all current nonspecific immunosuppressive protocols are formidable. In addition, the shortage of cadaver kidneys for transplantation has led to an increasing use of living related and unrelated donors, and stimulated a major research activity in xenotransplantation in an attempt to bring it to the clinic in the not too distant future.

Transport and biocompatibility characteristics are two important considerations when choosing hemodialysis membranes. Dialyzer performance depends on clearances of small solutes, middle molecules, and oncotically active proteins. Although complement and neutrophil activation have become the gold standards for biocompatibility testing of dialysis membranes, alterations of other cellular and noncellular blood elements as a result of blood-membrane interactions are also important. Because of concerns about middle molecule transport and biocompatibility, the original cellophane membrane has been gradually replaced by modified cellulosic membranes and synthetic membranes for clinical use. Recent studies suggest that the choice of dialysis membrane influences the clinical outcome of patients in several areas, including intradialytic acute anaphylactoid reactions, beta 2-microglobulin associated amyloidosis, recovery from acute renal failure, and mortality of chronic hemodialysis patients. However, the relative contributions of middle molecule transport, biocompatibility, and other factors in determining these differences in outcome are unclear. Future development of hemodialysis membranes should focus on improving biocompatibility and enhancing clearances of small solutes and middle molecules, while minimizing the loss of larger plasma proteins.

The use of dietary protein restriction for renal failure has fluctuated during the past 125 years. These fluctuations reflect not only the state of medical knowledge but also social, economic, and cultural factors. Factors inhibiting use of dietary treatment have been its status as an aspect of hygiene rather than as active therapy; the opinions of dominant practitioners and scientists around midcentury, including a presumption that renal adaptation to a high-protein diet must be appropriate; fear of malnutrition and a cultural belief in the virtue of dietary protein; unwillingness by physicians and patients to restrict consumption or lifestyle; and professional identification with the technologies of dialysis and renal transplantation. Factors promoting dietary treatment have been rediscovery of previous work on protein-induced renal injury; a sense that homeostatic compensations could have adverse consequences; federal incentives to curb consumption of scarce resources such as renal dialysis; and the integration of research on, and therapeutic use of diet into scientific medicine. A large ongoing study of dietary protein restriction to limit renal injury will add to our knowledge of this treatment; its application will surely be informed by social and cultural considerations.

As dialysis technology advanced, physicians trained in the new specialty of nephrology set up dialysis programs in hospitals throughout New Jersey. Physicians, state legislators, organizations, and patients contributed to the growth of a life-saving technology.

The first successful transplantation of a kidney from an alive relative donor in the USSR was performed by B. V. Petrovsky at the All-Union Research Institute of Clinical and Experimental Surgery (now the All-Union Surgery Research Center, AMS, USSR) on April 15, 1965. In November, 1965 he transplanted a cadaver kidney for the first time with a good outcome. The Center possesses an experience with 987 kidney transplantations to date, among which 101 were related transplantations. The authors discuss the progress made in this field of surgery in a period of 25 years. The longest survival period among recipients with a functioning related kidney is 22 years and among those with a cadaver kidney, 19 years. With the use of Cy A 86% of transplanted related kidneys and 76% of cadaver kidneys function for 12 months or longer. The authors discuss the advantages of a new original method for transorganic oxygen preservation of a kidney suggested by G. A. Asoyan, instrumental-functional methods developed at the Center for appraising the hemodynamics of the transplanted kidney and diagnosis of the rejection crisis, cyclosporine nephrotoxicity, and progress in the techniques of kidney transplantation and immunosuppressive therapy. The authors believe that further improvement in the results of allogeneic kidney transplantation is well-grounded.

It is commonly believed that atherogenesis is accelerated in patients with chronic renal failure during treatment by long-term dialysis or renal transplantation. However, several recent studies have failed to confirm this concept, despite the fact that overall atherosclerotic deaths in these patients are much higher than in the normal population. The natural history of atherogenesis in renal failure becomes much clearer if one analyses autopsy series of the pre-dialysis era. It is apparent from such studies that atheroma is frequent in renal failure before the development of terminal uraemia and that hypertension emerges as the major risk factor. Subsequent atherosclerotic deaths during long-term dialysis or renal transplantation may reflect progression of previously acquired atheroma, but do not per se indicate that atherogenesis has been accelerated after the commencement of renal replacement therapy. A proper appreciation of the natural history of atheroma in renal failure may permit a more rational approach to therapeutic intervention.

Clinical concepts--labels placed on categories of sickness--are essential to both the physician's and the patient's understanding of a disease. The changing use of labels in renal medicine reflected how physicians and others thought about kidney disease, each new label suggesting increasing complexity in the encounter of renal patient and physician. While dropsy referred to symptoms easily perceived by the patient as well as the physician, Bright's disease focused mainly on microscopic pathology invisible to the patient. Most removed from palpable symptoms is end-stage renal disease, a diagnosis often uncovered by autoanalyzer, defined by the need for dialysis, and formally bestowed by government. This process of definition and redefinition demands the attention of scholars because it reveals much about the evolution of medical thought and practice.