Given the Science on Malnutrition, How Does the Clinician Respond? Practical Lessons for and Application to the Dialysis Patient

Abstract

Nephrologists are only too accustomed to watching functional decline in patients who undergo long-term hemodialysis. This decline is the consequence of a complex series of biochemical and pathophysiologic processes that lead to decreased appetite, reductions in serum proteins, and loss of muscle mass and often results in fatigue, as well as reductions in stamina, exercise tolerance, and overall quality of life. This constellation of problems has been referred to by a variety of terms: protein-energy malnutrition, cachexia, muscle wasting, or simply malnutrition. This lack of precision in nomenclature surely adds to uncertainty in recognition and diagnosis. In most of cases, though, underlying causes are complicated and clearly not simply due to insufficient caloric intake. This may be a major reason that we as physicians have not been particularly successful in preventing or ameliorating these problems in our patients with ESRD. Here we review the potential causes of this functional decline at the molecular level and the current therapeutic approaches for prevention and treatment. It is our hope, of course, that extending our basic molecular knowledge of these processes will translate into better markers and more directed therapies for the catabolic dialysis patient in the not-too-distant future. The fundamental issue underlying the malnutrition that is seen in the ESRD population is that these patients are catabolic , meaning rates of protein breakdown outstrip production of new body protein. Isotope studies in experimental animals and humans with uremia show that overall rates of protein synthesis generally are unchanged, whereas rates of protein degradation tend to increase (1,2). Because the rates of protein turnover in cells are very high (3.5 to 4.5 g protein/kg per d) (3), more than three times the average daily protein intake, even small increases in proteolysis can cause marked protein depletion. Because most body stores of …