Nutritional Supplementation Acutely Increases Albumin Fractional Synthetic Rate in Chronic Hemodialysis Patients
Journal of the American Society of Nephrology
Uremic malnutrition is associated with increased risk of hospitalization and death in chronic hemodialysis (CHD) patients. Most nutritional intervention studies in CHD patients traditionally have used concentrations of serum albumin as the primary outcome measure and showed slight or no significant improvements. A recent study showed that intradialytic parenteral nutrition (IDPN) improves whole-body protein synthesis in CHD patients. On the basis of this observation, it was hypothesized that
... ypothesized that the anabolic effects of IDPN are associated with increases in the fractional synthetic rate of albumin, a direct estimate of acute changes in hepatic albumin synthesis. Seven CHD patients were studied during two hemodialysis (HD) sessions, with and without IDPN, using primed-constant infusion of ( 13 C) leucine 2 h before, during, and 2 h after HD. Plasma enrichments of ( 13 C) leucine and ( 13 C) ketoisocaproate were examined to determine the fractional synthetic rate of albumin. The results indicate that administration of IDPN significantly improves the fractional synthetic rate of albumin during HD (16.2 Ϯ 1.5%/d versus 12.8 Ϯ 1.7%/d; P Ͻ 0.05) in CHD patients in parallel with significant improvements in whole-body protein synthesis (5.05 Ϯ 1.3 mg/kg fat-free mass/ min versus 3.22 Ϯ 0.3 mg/kg fat-free mass/min; P Ͻ 0.05). IDPN is protein anabolic in the acute setting in CHD patients, as evidenced by significant concomitant increases in the fractional synthetic rate of albumin and whole-body protein synthesis. Uremic malnutrition is associated with increased risk of hospitalization and death in chronic hemodialysis (CHD) patients (1,2). Most nutritional intervention studies in CHD patients traditionally have used concentrations of serum albumin as a clinical evaluation of overall protein homeostasis because of its established and significant association with outcomes (3). However, serum albumin concentrations can be difficult to interpret in certain instances, such as presence of inflammatory response and altered fluid state as observed in CHD patients. Furthermore, serum albumin has a relatively long half-life. Not surprising, most studies that have evaluated the effects of nutritional intervention on serum albumin in CHD patients have shown slight or no significant improvements in the serum concentrations of this protein. We recently showed that intradialytic parenteral nutrition (IDPN) improves whole-body protein synthesis in CHD patients. Because albumin is a prominent protein circulating throughout the body, it is likely that the improvements in whole-body protein as a result of nutritional supplementation are linked with increases in visceral synthesis of albumin. The fractional synthetic rate (FSR) of albumin provides a direct estimate of acute changes in hepatic albumin synthesis. To our knowledge, no study to date has examined the effects of nutritional supplementation on the FSR of albumin in CHD patients. In this study, we hypothesized that the anabolic effects of IDPN may be associated with increases in albumin FSR beyond what could be observed with the hemodialysis (HD) procedure alone. To test this hypothesis, we studied seven CHD patients during two HD sessions, with and without IDPN, using stable isotope infusion techniques for protein turnover assessment. Our results indicate that administration of IDPN significantly improves the FSR of albumin in CHD patients in parallel with marked improvement in whole-body protein synthesis. Materials and Methods Patients Patients were recruited from the Vanderbilt University Outpatient Dialysis Unit. Inclusion criteria for the study were patients who had been on a thrice-weekly CHD program for Ͼ6 mo, using a biocompatible HD membrane (Fresenius F80) and an adequate dose of dialysis (single pool Kt/V Ն1.4). Patients who had active infectious or inflammatory disease, had liver failure of any cause, were hospitalized within 3 mo before the study, had recirculation in the vascular access and/or vascular access blood flow Ͻ750 ml/min detected on the arteriovenous (AV) shunt, and were receiving steroids and/or immunosuppressive agents were excluded. The whole-body protein synthesis data in this article is derived from seven patients, six of whom were included in our previous publication (4).