Impact of albumin synthesis rate and the acute phase response in the dual regulation of fibrinogen levels in hemodialysis patients.

BACKGROUND: Fibrinogen is a risk factor for cardiovascular disease. It also is an acute phase protein (APP) and its plasma concentration increases with inflammation. Fibrinogen synthesis correlates with albumin synthesis in nephrotic patients and in patients with an expanded plasma volume even when serum albumin is normal and there is no inflammatory disease. The relationships among albumin synthesis, the acute phase response and plasma fibrinogen levels in hemodialysis patients are unknown.

METHODS: In 74 hemodialysis patients, albumin synthesis, plasma volume (PV) and acute phase proteins (APPs) C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1 AG), ceruloplasmin (Cer), and interleukin 6 (IL-6) were measured in serum and fibrinogen in plasma, and the results analyzed by multiple regression analysis. CRP, IL-6, alpha1 AG, Cer and fibrinogen were measured monthly, which enabled us to determine whether changes in these APPs correlated with the levels of and variability in plasma fibrinogen over time using a longitudinal modeling approach. Length of follow-up for the 74 patients ranged from 3.25 to 67.5 months.

RESULTS: Baseline fibrinogen (548.6 +/- 106. 4 mg/dL) was significantly greater than levels reported for normal adults and correlated positively with albumin synthesis (P < 0.001), age (P < 0.001) and log CRP (P = 0.002) and negatively with PV (P < 0.001). Longitudinally, fibrinogen varied positively with long-lived APPs, Cer and alpha1 AG, as well as the short-lived APP, CRP.

CONCLUSION: Plasma fibrinogen concentration is high in HD patients and directly correlates with increased albumin synthesis rates and the serum levels of APPs. Fibrinogen levels also correlate negatively with PV. Fibrinogen levels vary over time in synchrony with levels of other long-lived APPs, supporting the hypothesis that fibrinogen is regulated in part as a component of the acute phase response and in part by factors that increase albumin synthesis.