Abstract: Before 1960, end-stage renal disease was uniformly fatal. However, with the development by Wayne Quinton and Belding Scribner of an external shunt to provide repeated vascular access and the use of dialysis technology that had evolved some years earlier for the treatment of acute renal failure, long-term intermittent hemodialysis for the management of end-stage renal disease was launched in March 1960 at the University of Washington. The application of peritoneal dialysis for the management of the disease soon followed. A little over a decade elapsed before Congress legislated the provision of Medicare coverage, regardless of the patient's age, for the treatment of the disease. These and subsequent events have made it possible for hundreds of thousands of patients with the disease to receive life-sustaining renal replacement therapy. The incidence of treated end-stage renal disease in the United States is 180 cases per 1 million persons and continues to increase at a rate of 7.8% per year. In 1990, more than 45 000 new patients with end-stage renal disease were enrolled in the Medicare program, of which 66% were white, 28% were African-American, 2% were Asian or of Pacific Island descent, and 1% were Native Americans. Forty-three percent of the patients were at least 64 years of age, and fewer than 2% were younger than 20 years of age. On average, African-American and Native American patients are younger at the onset of treated disease and show dramatically higher incidence rates than do white or Asian or Pacific Island patients. Although clinical experience suggests that the incidence in Hispanics is also greater than that in whites, data from the United States Renal Data System are not available to confirm this clinical impression. Hypertension and diabetes accounted for 63% of the new cases in 1990. The incidence of cases of diabetic end-stage renal disease in Native Americans was almost twice that of African-Americans and six times that of whites. Of the more than 195 000 patients with end-stage renal disease receiving renal replacement therapy during 1990, 70% were treated with either hemodialysis or peritoneal dialysis. Although kidney transplantation is the treatment of choice for many patients with end-stage renal disease, the increase in time spent waiting for cadaveric organs, the presence of disqualifying comorbid conditions, and the low transplantation rates in an aging population will probably ensure that dialysis remains the primary method of renal replacement therapy in the foreseeable future. According to federal, state, and private funding sources, the cost for care of patients with the disease was approximately $7.26 billion in 1990, an increase of 21% over a similar estimate for the previous year. Not reflected in this figure are additional expenditures for outpatient drugs and supplies, the cost of disability, and Social Security payments. As the U.S. population continues to grow and a larger proportion of the population at risk reaches age 65 years and older, the cost of kidney disease, including this end-stage component, is projected to increase. According to an analysis done by the Health Care Financing Administration, by the turn of the century it is estimated that more than 300 000 patients will be enrolled in the program. Furthermore, 85 000 new patients will enter the program in the year 2000 alone. Most of the increase will come from the elderly and the diabetic population. Despite improvements in dialysis technology over the past decade, mortality remains high. For example, at age 49 years, the expected duration of life of a patient with end-stage renal disease is 7 additional years compared with approximately 30 additional years for a person of the same age from the general population. In addition to increased mortality, patients also experience significantly greater morbidity, including a substantial loss in quality of life. In 1986, for example, for all Medicare patients older than 65 years, hospitalization averaged 2.8 days per year, whereas the median time for patients who have received 1 year of dialysis was 15.0 days per year. The relevant information available to prescribe the appropriate dialysis dose is limited and subject to gross errors. Thus, what constitutes an adequate dialysis dose remains a controversial question among professionals caring for patients receiving dialysis. To resolve questions about delivered dialysis dose, comorbid conditions, and dialysis-related complications, all of which appear to cause increased morbidity and mortality in U. S. patients receiving dialysis compared with those in certain European countries and Japan, the National Institute of Diabetes and Digestive and Kidney Diseases and the Office of Medical Applications of Research of the National Institutes of Health convened a consensus development conference on 1 to 3 November 1993. After one and a half days of testimony by experts in the field, a consensus panel representing the professional fields of general medicine, nephrology, pediatrics, biostatistics, nutrition, and nursing, and a representative of the public considered evidence and agreed on answers to the following questions: 1) How does early medical intervention in predialysis patients influence morbidity/mortality? 2) What is the relationship between delivered dialysis dose and morbidity/mortality? 3) Can comorbid conditions be altered by nondialytic interventions to improve morbidity/mortality in dialysis patients? 4) How can dialysis-related complications be reduced? and 5) What are the future directions for research in dialysis? How Does Early Medical Intervention in Predialysis Patients Influence Morbidity/Mortality? It is clear that factors influencing the morbidity and mortality of patients receiving dialysis exist for an extended period before end-stage renal disease develops and the need for dialysis is imminent. Unfortunately, few patients (20% to 25%) are referred to a renal physician before dialysis therapy begins. Managed care programs must recognize the importance of the continued involvement of the renal team in the care of these patients. Several conditions related to renal failure are present before dialysis therapy begins, including anemia, hypertension, malnutrition, renal osteodystrophy, lipid abnormalities, and metabolic acidosis. In addition, smoking and poor glycemic control in diabetic patients will influence subsequent morbidity and mortality. The costs of delayed referral include both emergency dialysis, with its higher morbidity and mortality, and excessive use of health care dollars. Emergency dialysis jeopardizes the choice of the mode of dialysis, endangers the ability to maintain prolonged vascular access, precludes psychological preparation of the patient for care, and necessitates hospitalization for a catastrophic complex illness. The mortality in this crisis situation can be as high as 25%. In the patient with progressing renal insufficiency, early intervention should be aimed at reversal of hypertension and correction of identified nutritional deficiencies and acidosis. Although data are limited, the use of erythropoietin will prevent severe anemia and may reverse its associated complications. No consensus exists on the ultimate role of dietary protein restriction in slowing the progression of renal failure. However, an intake protein level of 0.7 to 0.8 g/kg per day can maintain nutritional status in noncatabolic patients with end-stage renal disease without placing an undue burden on the capacity to eliminate potentially toxic metabolites, including acid, potassium, sulfate, phosphorus, magnesium, and unidentified uremic toxins. Because of the deleterious effects of parathyroid hormone, therapies aimed at prevention or reversal of secondary hyperparathyroidism should be initiated before dialysis therapy begins. A patient should be referred to a nephrologist when the serum creatinine level has increased to 1.5 mg/dL in women and to 2.0 mg/dL in men. Later, referral to a renal team consisting of a nephrologist, dietitian, nurse, social worker, and mental health professional allows time to establish a working relationship, to acquaint the patient with the various modes of renal replacement therapy, and to provide information on dialysis access, nutritional modification, avoidance of potentially nephrotoxic drugs, and potential financial support for services. To reduce mortality and morbidity as soon as possible, it is essential to initiate the medical interventions discussed below. Hypertension Increasing evidence suggests that aggressive treatment of hypertension in the period before dialysis therapy begins delays progression of renal disease and is the most potent intervention to decrease subsequent cardiovascular mortality in patients receiving dialysis. As in patients without renal disease, hypertension is the most important etiologic factor in the development of left ventricular hypertrophy and diastolic dysfunction. It has been proposed that delay of adequate therapy or failure to lower blood pressure to normal over several years results in changes that become irreversible or only slowly reversible with dialysis. Hypertension is the highest risk factor for coronary artery disease and cerebral vascular disease. The goal of therapy is a normal systolic and diastolic pressure. Anemia Studies now suggest that aggressive treatment of anemia in the period before dialysis therapy begins is as important as treatment during dialysis. In fact, to reduce cardiovascular morbidity and mortality, this therapy may be critical because long-standing left ventricular hypertrophy associated with anemia may be poorly reversible or irreversible if therapy is delayed until dialysis therapy begins. In addition, correction of anemia before dialysis therapy starts appears to improve or maintain functional capacity, nutritional adequacy, sexual function, and psychological health. It also reduces the risk for hepa