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The Microinflammatory State of Uremia

In a rarely cited communication, Degoulet et al. [1] analyzed the predictors of death in a prospective French study of hemodialysis patients. As shown in table 1, they obtained the paradoxical result that the higher the serum cholesterol concentration, the better patient survival. He correctly concluded that this does not mean that a high cholesterol concentration per se was beneficial. Rather he proposed that the effect of the serum cholesterol concentration was confounded by other factors, particularly malnutrition. This hypothesis is supported by the observation that an inverse relation was noted between body mass index (BMI) and survival. Following this communication, a number of studies, using various methodologies, confirmed a relation between indices of malnutrition and survival. Such indices comprise body mass index, anthropometric measurements, assessment of dietary intake, protein catabolic rate, but also more easily measurable markers of reputed visceral protein deficiency, such as low concentrations of plasma albumin, IGF-1, transferrin and others. In a recent study from the Karolinska Institute [2] most of these plasma indicators were correlated with malnutrition-related items, such as global nutritional assessment, body weight, skin-fold thickness, midarm muscle circumference, handgrip strength, plasma-free amino acids, etc. One has to raise the issue, however, whether these indices are specific for pure malnutrition. And, furthermore, which causal link exists between malnutrition and cardiovascular death. It is simple to envisage that malnutrition may be disadvantageous in the defence against infections and other insults, but most dialysis patients do not succumb to infections, but to cardiovascular events. So the enigma remains how malnutrition is related to increased cardiac, particularly increased coronary, risk. Certainly cardiac death is not a major health issue in underdeveloped countries, where malnutrition is rampant. Furthermore, in nonrenal patients Folsom et al. [3] found no relation between serum albumin and cardiovascular disease, suggesting that low albumin per se does not directly contribute to cardiovascular mortality. Could it be that these indices, including low plasma albumin, are nonspecific and that the link between these markers, in the past interpreted as evidence of malnutrition, and cardiac death is more indirect?