Protein-energy malnutrition in dialysis patients

PROTEIN-CALORIE or protein-energy malnutrition (PEM) has been shown to be highly prevalent in hospitalized patients in association with disease whether due to medical1 or surgical2 illness. Ambulatory outpatients with systemic diseases also commonly display the two principal hallmarks of PEM, unintentional weight loss and hypoalbuminemia.3 Prevalence rates of 25% to 50% also have been defined in various surveys among maintenance hemodialysis or peritoneal dialysis patients.4 Increased mortality has been clearly related to PEM in general surgical patients,5 general medical patients,6 and in those receiving maintenance hemodialysis.7 Clearly, the operative words in these introductory sentences are associated or related, not caused. The evidence that reversal of disease-related PEM is always possible is much less certain; without correction of PEM by otherwise adequate nutritional support, the data suggest that minimal, if any, improvement in prognosis is likely.8,9 What are the reasons for this barrier to nutritional repletion, and can we estimate the likelihood of success for nutritional therapies a priori? It is helpful, we believe, to describe the principal underlying reasons for disease-related PEM to define the pathophysiology of nutritional repletion. Two mechanisms define the development of PEM, semistarvation and the systemic inflammatory response. Semistarvation refers to inadequate caloric or protein intake. Whenever either is limiting, and generally both are in diseaserelated PEM, loss of lean body mass invariably follows. In the two-compartment model of body composition, lean body mass (75% to 80% of body weight) is the larger component, consisting of nitrogen-containing tissues and their accompanying fluid, with fat being the remainder. Morbidity and mortality are the most clearly linked to loss of body mass and not to the size of the fat compartment. Factors contributing to semistarvation in end-stage renal disease are mainly those producing anorexia, including medications, dialysis, inadequate dialysis, socioeconomic factors, depression, and toxic metabolic products.4 In addition, there are modest amino-acid or protein losses in hemodialysis and peritoneal dialysis, respectively.4 Were these to be the only factors in the development of PEM in end-stage renal disease, the condition could be completely reversed by adequate nutritional intake whether accomplished volitionally by diet counseling or nutritional supplements or invasively by enteral or rarely parenteral feeding. However, the most common causative mechanism for the development of disease-related PEM is the systemic inflammatory response (SIR). The SIR syndrome has been defined objectively by a Consensus Conference as being present when two criteria for temperature, pulse rate, respiratory rate, and leukocyte count are met.10 The SIR develops through neuroendocrine responses characterized by enhanced release of so-called mobilizing hormones, particularly catecholamines, corticosterone, glucagon, and growth hormone, that serve to mobilize tissue stores of fuel, including glucose, fatty acids, and amino acids. In addition, there is stimulation of cytokine production in many tissues arising principally from the monocyte/macrophages line after activation by any number of diverse stimuli, including microorganisms (bacteria, fungi, protozoa, viruses), endotoxin, techoic acid, various chemicals, complements, antigen-antibody complexes, and numerous disease states, including infection, trauma, cancer, inflammatory disorders, and autoimmune, cardiac, liver, and renal diseases. Cytokines are intercellular messengers characterized by small size (8 to 30 kd), activity in picomolar quantities, production by many different cells, de novo production, amplification through cascade, and mainly autocrine and paracrine action. The principal proximate cytokines are interleukin-1 (IL-1) and tumor necrosis factor (TNF), which stimulate more than 20 cytokines already described to orchestrate the SIR From the Departments of Medicine and Surgery, Beth Israel Deaconess Medical Center, Boston, MA. Received September 11, 1998; accepted as submitted September 14, 1998. Address reprint requests to Bruce Bistrian, MD, PhD, Departments of Medicine and Surgery, Beth Israel Deaconess Medical Center, 1 Deaconess Rd, Boston, MA 02215. E-mail: bbistria@west.bidmc.harvard.edu 1999 by the National Kidney Foundation, Inc. 0272-6386/99/3301-0029$3.00/0