Coordinated increase in albumin, fibrinogen, and muscle protein synthesis during hemodialysis: role of cytokines

1 Department of Medicine, University of New Mexico Health Sciences Center, and 3 Division of Rheumatology, University of New Mexico, Albuquerque 87131; 2 Albuquerque Academy, Albuquerque, New Mexico 87109; and 4 Department of Surgery, University of Texas Medical Branch, Galveston, Texas 77550 Submitted 2 October 2003 ; accepted in final form 17 December 2003 Serum albumin, fibrinogen levels, and lean body mass are important predictors of outcome in end-stage renal disease (ESRD). We estimated the fractional synthesis rates of albumin (FSR-A), fibrinogen (FSR-F), and muscle protein (FSR-M) in nine ESRD patients and eight controls, using primed constant infusion of L -[ ring - 13 C 6 ]phenylalanine. Cytokine profile and arteriovenous balance of amino acids were also measured. ESRD patients were studied before (Pre-HD) and during hemodialysis (HD). Plasma IL-6, IL-10, and C-reactive protein increased significantly during HD. Despite a decrease in the delivery of amino acids to the leg, the outflow of the amino acids increased during HD. The net balance of amino acids became more negative during HD, indicating release from the muscle. HD increased leg muscle protein synthesis (45%) and catabolism (108%) but decreased whole body proteolysis (15%). FSR-A during HD (9.7 ± 0.9%/day) was higher than pre-HD (6.5 ± 0.9%/day) and controls (5.8 ± 0.5%/day, P < 0.01). FSR-F increased during HD (19.7 ± 2.6%/day vs. 11.8 ± 0.6%/day, P < 0.01), but it was not significantly different from that of controls (14.4 ± 1.4%/day). FSR-M intradialysis (1.77 ± 0.19%/day) was higher than pre-HD (1.21 ± 0.25%/day) and controls (1.30 ± 0.32%/day, P < 0.001). Pre-HD FSR-A, FSR-F, and FSR-M values were comparable to those of controls. There was a significant and positive correlation between plasma IL-6 and the FSRs. Thus, in ESRD patients without metabolic acidosis, the fractional synthesis rates of albumin, fibrinogen, and muscle protein are not decreased pre-HD. However, HD increases the synthesis of albumin, fibrinogen, and muscle protein. The coordinated increase in the FSRs is facilitated by constant delivery of amino acids derived from the muscle catabolism and intradialytic increase in IL-6. protein catabolism; protein turnover; inflammation; amino acid; endstage renal disease Address for reprint requests and other correspondence: D. S. C. Raj, Div. of Nephrology, ACC 5th Floor, Univ. of New Mexico Health Sciences Center, 2211 Lomas Blvd. NE, Albuquerque, NM 87131 (E-mail: draj{at