Interleukin-6 modulates hepatic and muscle protein synthesis during hemodialysis

Increased demand for amino acids to sustain acute-phase protein synthesis could be the stimulus for the increased muscle protein catabolism during hemodialysis (HD). This could be attenuated by intradialytic amino-acid infusion. To test this, we measured the fractional synthesis rates of albumin, fibrinogen, and muscle protein in eight patients with end-stage renal disease at baseline before dialysis and during HD without or with amino-acid infusion. The percentage change in the fractional synthesis rates of albumin, fibrinogen, and muscle protein from baseline was significantly higher during HD with amino-acid infusion than without amino-acid infusion. Leg muscle proteolysis was significantly increased during unsupplemented HD compared with baseline, but this was not decreased by amino-acid infusion. Arteriovenous balance studies across the leg showed a net efflux of interleukin-6 (IL-6) from the muscle into the vein during HD. The fractional synthesis rate of albumin, fibrinogen, and muscle protein correlated with each other and with the IL-6 efflux from the leg. Leg muscle protein catabolism was positively related to IL-6 release from the leg and not associated with amino-acid availability. Our results show that intradialytic cytokine activation and not amino-acid depletion is the major protein catabolic signal during HD.