Elimination of Waste Products of Metabolism and Drugs



As noted earlier, there is no consensus on the nature of the uremic toxins. Nonetheless, the di­etary intake of protein contributes to the genesis of uremic symptoms. While urea is not a toxic product in and of itself, the BUN concentration does correlate both with the dietary intake of pro­tein and with the systemic manifestations of endstage renal disease. It is generally believed that BUN reflects the accumulation of other products of protein catabolism, some of which may con­tribute to clinical symptoms. Restriction of die­tary intake of protein can lead to symptomatic im­provement in the nausea, vomiting, malaise, and encephalopathv of end-stage renal disease. Such improvements ‘are usually associated with a de­crease in BUN. On the other hand, uremic patients have a decreased protein anabolic rate and an in­creased rate of protein catabolism. Marked restric­tions in protein intake, therefore, can result in protein malnutrition. A patient with end-stage renal disease can usually be maintained in nitro­gen balance by restriction of the dietary intake of protein to 40 grams per day. Moreover, proteins providing essential amino acids (high biological value proteins) are indicated to stimulate the rein­corporation of urea nitrogen into new protein syn­thesis and prevent accumulation of nitrogen me­tabolites that are not essential. Additional calories need to be provided when protein intake is re­stricted. The use of a low-protein diet containing proteins of high biological value can lead to symp­tomatic improvement and prolong the time until a patient must have dialytic therapy or transplan­tation.

The kidney is a major route of excretion of drugs. Moreover, renal failure is associated with alterations in the binding of drugs by plasma pro­teins and in the overall metabolism and distri­bution of drugs within the body. These consid­erations are reviewed in Chapter 35.