ASN95 Hot Topic: Occult inflammation in hemodialyzed patients

The concentration of serum albumin s[alb] has been considered the most powerful predictor of death in hemodialyzed patients. Because low s[alb] is also a marker for protein-calorie malnutrition, the usual paradigm is that malnutrition causes a decline in health status that leads to death in hemodialyzed patients with low s[alb]. Recent studies by Kaysen et al (KI 48:510-16, Aug 1995) have challenged this concept. Comparing stable hemodialyzed patients with normal (4.2 g/dl) versus low (3.2 g/dl) s[alb] they showed that albumin synthetic rates were decreased in the low s[alb] group. The low s[alb] group also had elevated levels of the acute phase reactants alpha-2 macroglobulin and ferritin with a tendency for elevation of C-reactive protein (CRP). Nutritional status including dietary protein intake, protein catabolic rate, and caloric intake were the same in both groups. Since albumin is a well-established negative acute phase reactant, a concern was raised that all of these findings including the low s[alb] are due to an occult inflammatory process that may predispose to death.

Several abstracts were presented at the November ASN meetings in support of this concept. Studies reported by Bergstrom (2218, 573) showed that CRP was an equally if not more powerful predictor of death than s[alb] and nutritional status in 128 hemodialyzed patients followed for 4 years. A Cox proportional hazard model showed that s[alb] lost its significance as a predictor of mortality when corrected for CRP. In another report from the same institution (995,586) Qureshi and his colleagues found a significant negative correlation between s[alb] and CRP in the same population. CRP was an equally powerful predictor of s[alb] as nutritional status, suggesting that non-nutritional factors associated with the acute phase response are responsible for the low s[alb]. Bologa et al (996,573) showed in a population of 94 hemodialyzed patients that predialysis levels of TNF-alpha correlated inversely with s[alb] and cholesterol levels. During the following year patients with relatively high TNF-alpha and IL-6 levels had higher mortality supporting the hypothesis that inflammatory cytokines mediate the hypoalbuminemia, hypocholesterolemia, and mortality in hemodialyzed patients. (Thomas A. Depner)

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