Inflammation and reduced albumin synthesis associated with stable decline in serum albumin in hemodialysis patients

Background. The concentration of albumin in serum is maintained by its rates of synthesis, catabolism, and distribution between vascular and extravascular compartments. Albumin synthesis is suppressed when there is inflammation or inadequate protein intake. This study was conducted to establish whether a decline in serum albumin of > 0.3 g/dL was accompanied by a change in albumin synthesis and if so whether these changes were associated with increased levels of acute phase proteins and/or with a decrease in equilibrated normalized protein catabolic rate (enPCR). Methods. Seventy-nine patients in the National Institutes of Health (NIH)-sponsored HEMO Study had baseline measurements of albumin synthesis (measured kinetically as the disappearance of [(125)]I human serum albumin), the serum concentrations of albumin, transferrin, C-reactive protein (CRP), a 1 acid glycoprotein (alpha1AG), ceruloplasmin, interleukin-6 (IL-6), plus monthly measurements of enPCR. The plasma levels of all proteins and enPCR were measured regularly over 2 years or until serum albumin decreased by > 0.3 g/dL on two sequential measurements. Albumin synthesis was measured a second time when serum albumin declined by > 0.3 g/dL or after 2 years. Results. Fifty-nine patients [21 with a significant decrease in serum albumin (decliners) and 38 with stable values of serum albumin] had albumin synthesis measured twice. A decline in albumin concentration and synthesis was associated with an increase in alpha1AG when data from all patients were analyzed as a group. In decliners, albumin synthesis decreased significantly but was unchanged in stable. Likewise, in decliners, IL-6, CRP, alpha1AG, and ceruloplasmin increased significantly but were unchanged in stable. enPCR was unchanged in both groups and was not associated with either changes in albumin level or synthesis in the whole group. Conclusion. A decrease in serum albumin of > 0.3 g/dL that persists for a period of 6 weeks is associated a decrease in albumin synthesis. This response is associated with evidence of activation of the acute phase response (inflammation) but not with changes in enPCR. In well-dialyzed patients, inflammation is the principal cause of a decrease in serum albumin while protein intake plays an insignificant role.