Malnutrition: a frequent misdiagnosis for hemodialysis patients
Authors: William E. Mitch
Journal: Journal of Clinical Investigation (2002)

Precision in the use of words is necessary in any discipline, and this holds true for physicians and investigators dealing with patients who have chronic kidney disease. Specifically, malnutrition is often used to describe a group of abnormalities — fatigue, loss of body weight with muscle mass being replaced by fatty tissue, declining serum proteins — present in many such patients. However, malnutrition is defined as the consequence of insufficient food or an improper diet and is generally a misdiagnosis for patients with chronic kidney disease. The mechanisms for these abnormalities are complex and have not been fully identified, but diagnosing them as malnutrition is deeply misleading since it suggests that the abnormalities can be overcome simply by supplying more food or altering the composition of the diet. To date, this approach has not proven to be successful. The investigation of dialysis patients by Pupim et al. in this issue of the JCI shows why such consequences of kidney failure result from mechanisms more complex than malnutrition (1). Their results show that a sharp increase in protein and calorie intake during dialysis produces only a transient benefit, even for end-stage renal disease (ESRD) patients with few signs of abnormal protein metabolism.

The development of progressive kidney disease raises complex problems requiring constant attention to avoid and treat complications from lost kidney function including anemia, bone disease, abnormalities in electrolytes, and, of course, the almost universal appearance of hypertension. Worse yet, when ESRD develops, the patient is at risk of the sharp increase in mortality associated with dialysis. Cross-sectional analyses of patients in dialysis units indicate that the signs and symptoms commonly attributed to malnutrition occur in 50% or more of these patients (2, 3).

In children with kwashiorkor or adults with severe malnutrition, many of these same abnormalities can be ameliorated when dietary protein or nitrogen is provided (4). When they occur in ESRD patients, do they also result from too little food or an improper diet? The first step in addressing this question is to determine whether some other, more fundamental abnormality arising in patients with kidney disease prevents them from utilizing dietary nutrients effectively. Normal adults characteristically respond to the restriction of dietary protein by progressively decreasing the irreversible destruction of amino acids and, consequently, the production of urea from the nitrogen of amino acids. At the limits of this adaptive response, another mechanism is activated, leading to a decrease in the degradation of protein and at least some stimulation of protein synthesis (5). These adaptive responses act to maintain protein balance, and, unless there is severe dietary restriction, they usually suffice to prevent the loss of body proteins. Fortunately, patients with uncomplicated kidney disease, including nephrotic subjects, can activate the same adaptations to dietary protein restriction and maintain protein balance and lean body mass for long periods while they are eating protein-restricted diets (6–10). However, when dialysis becomes necessary, the amounts of protein and energy required to achieve protein balance increase sharply, and it is not known if these adaptive responses occur in ESRD patients or how effective they are in preventing excessive catabolism (11).