Increased albumin and fibrinogen synthesis rate in patients with chronic renal failure.
BACKGROUND
Hypoalbuminemia and hyperfibrinogenemia are frequently observed in patients with chronic renal failure (CRF) and are both associated with cardiovascular diseases. The mechanisms responsible for hypoalbuminemia and hyperfibrinogenemia in CRF are unknown.


METHODS
In the present study, both albumin and fibrinogen kinetics were measured in vivo in predialysis patients (N = 6), patients on peritoneal dialysis (N = 7) and control subjects (N = 8) using l-[1-13C]-valine.


RESULTS
Plasma albumin concentration was significantly lower in patients on peritoneal dialysis compared to control subjects (P < 0.05). Plasma fibrinogen was significantly increased in both predialysis patients (P < 0.01) as well as patients on peritoneal dialysis (P < 0.001) in comparison to control subjects. In contrast to albumin, fibrinogen is only lost in peritoneal dialysate and not in urine. The absolute synthesis rates (ASR) of albumin and fibrinogen were increased in patients on peritoneal dialysis (ASR albumin, 125 +/- 9 mg/kg/day versus 93 +/- 9 mg/kg/day, P < 0.05; ASR fibrinogen, 45 +/- 4 mg/kg/day versus 29 +/- 3 mg/kg/day, P < 0.01) compared to control subjects. Albumin synthesis is strongly correlated with fibrinogen synthesis (r2 = 0.665, P < 0.0001, N = 21). In this study, the observed hypoalbuminemia in patients on peritoneal dialysis is likely not explained by malnutrition, inadequate dialysis, inflammation, metabolic acidosis, or insulin resistance. We speculate that peritoneal albumin loss is of relevance.


CONCLUSIONS
Synthesis rate of albumin and fibrinogen are coordinately up-regulated. Both albumin and fibrinogen are lost in peritoneal dialysis fluid. To compensate protein loss, albumin synthesis is up-regulated, but the response, in contrast to predialysis patients, does not fully correct plasma albumin concentrations in peritoneal dialysis patients. The increase in fibrinogen synthesis introduces an independent risk factor for atherosclerosis, since plasma fibrinogen pool is enlarged.
Prinsen
Berthil H C M T
BH
Department of Vascular Medicine and Metabolism, University Medical Center Utrecht, Utrecht, The Netherlands. B.Prinsen@azu.nl
Rabelink
Ton J
TJ
Beutler
Jaap J
JJ
Kaysen
George A
GA
De Boer
Jose
J
Boer
Walther H
WH
Hagen
E Christiaan
EC
Berger
Ruud
R
De Sain-Van Der Velden
Monique G M
MG
D000328:Adult; D000419:Albuminuria / Q000150:complications; D016022:Case-Control Studies; D015314:Dialysis Solutions / Q000737:chemistry; D005260:Female; D005340:Fibrinogen / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D034141:Hypoalbuminemia / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000009:adverse effects; D012709:Serum Albumin / Q000096:biosynthesis*; D015854:Up-Regulation
D015314:Dialysis Solutions; D012709:Serum Albumin; D005340:Fibrinogen