1316 MEDICAL PROGRESS Uremia

Copyright © 2007 Massachusetts Medical Society. Medical progress has altered the course and thus the definition of uremia, which once encompassed all the signs and symptoms of advanced kidney failure. Hypertension due to volume overload, hypocalcemic tetany, and anemia due to erythropoietin deficiency were once considered signs of uremia but were removed from this category as their causes were discovered. Today the term “uremia” is used loosely to describe the illness accompanying kidney failure that cannot be explained by derangements in extracellular volume, inorganic ion concentrations, or lack of known renal synthetic products. We now assume that uremic illness is due largely to the accumulation of organic waste products, not all identified as yet, that are normally cleared by the kidneys. No specific time point demarcates the onset of uremia in patients with progressive loss of kidney function. The features of uremia identified in patients with end-stage kidney failure may be present to a lesser degree in people with a glomerular filtration rate that is barely below 50% of the normal rate, which at 30 years of age ranges between 100 and 120 ml per minute per 1.73 m2 of body-surface area. Thus, in the United States alone, uremic symptoms may be present to some degree in an estimated 8 million people who have a glomerular filtration rate below 60 ml per minute per 1.73 m2 of body-surface area.1 However, early symptoms of uremia, such as fatigue, are nonspecific, making the condition difficult to identify. At present, moreover, we can slow progression to kidney failure but can treat uremia only by replacing kidney function. Thus, the question of whether a patient has uremia comes down to whether dialysis or a transplant would be beneficial. Treatment of uremia is now dominated by dialysis, in large part because donor kidneys are in short supply. In the United States in 2004, approximately 100,000 people began receiving kidney-replacement therapy for end-stage renal disease, and 335,000 people were receiving ongoing treatment with dialysis.2 In some cases, patients are treated with dialysis for decades, but overall outcomes are disappointing. The 5-year survival rates between 1995 and 1999 were under 35% for both hemodialysis and peritoneal dialysis. Patients treated with dialysis are hospitalized on average twice a year, and their quality of life is often low. Not all of the illness of a patient undergoing dialysis can be ascribed to uremia. Indeed, the evolution of dialysis has made the effects of uremia more difficult to distinguish, since the severity of classic uremic symptoms is attenuated. Instead, patients undergoing dialysis now have a new illness, which Depner3 aptly named the “residual syndrome.” This illness comprises partially treated uremia; ill effects of dialysis, such as fluctuation in the extracellular fluid volume and exposure to bioincompatible materials; and residual inorganic ion disturbances, including acidemia and hyperphosphatemia. In many patients, the residual syndrome is complicated by the effects of advancing age and systemic diseases that were responsible for the loss of kidney function. Although patients undergoing dialysis have a complex illness, there are compelling reasons to believe that inadequate removal of organic wastes is an important con-