PROPORTIONATE INCREASE OF FIBRINOGEN AND ALBUMIN SYNTHESIS IN NEPHROTIC PATIENTS - MEASUREMENTS WITH STABLE ISOTOPES

Hyperfibrinogenemia is a common feature of the nephrotic syndrome, and contributes to increased tendency for thrombosis and atherosclerosis. Its genesis is not certain, but the increase in liver fibrinogen mRNA in nephrotic rats indicates increased synthesis. Data in humans are s carce. We presently compared synthesis rates of fibrinogen and albumin in nephrotic adults (N = 7; plasma albumin 22.3 +/- 0.7 g/liter, prot einuria 12 g/day) and healthy control subjects (N = 8) using a primed/ continuous infusion of the stable isotope L-[1-C-13]valine for six hou rs. Absolute synthesis rate (ASR) of fibrinogen was 31 +/- 3 mg/kg/day in nephrotic subjects and 21 +/- 1 mg/kg/day in control subjects (P < 0.05), and positively correlated with plasma fibrinogen (P = 0.0317). The plasma fibrinogen pool was disproportionately increased in the ne phrotic patients (271 +/- 30 mg/kg) compared to the controls (126 +/- 8 mg/kg), suggesting decreased fractional catabolic rate as well. The ASR of albumin was increased from 71 +/- 4 mg/kg/day in the controls t o 160 +/- 19 mg/kg/day in the patients (P < 0.0001), and strongly corr elated with the ASR of fibrinogen (P = 0.0046). Plasma alpha(2)-macrog lobulin was also elevated and correlated with the albumin synthesis ra te, whereas plasma serum amyloid A and C-reactive protein were not ele vated. These data suggest that in nephrotic patients the increased alb umin synthesis is associated with an increase in synthesis of a specif ic and coordinated group of proteins, among which is fibrinogen.