Bioactive rather than total IGF-I is involved in acute responses to nutritional interventions in CAPD patients.

BACKGROUND: Inadequate food intake plays an important role in the development of malnutrition in continuous ambulatory peritoneal dialysis (CAPD) patients. Aim of the study. The aim of the study was to investigate in CAPD patients whether circulating insulin-like growth factor-I (IGF-I) bioactivity may offer a more sensitive index to acute nutritional interventions than total IGF-I. METHODS: An open-label, randomized, crossover study of 2 days-with a 1-week interval-was performed in 12 CAPD patients in the fed state to compare a mixture of amino acids (Nutrineal 1.1%) plus glucose (AA plus G) (Physioneal 1.36% to 3.86%) dialysate versus G only as control dialysate. Fed-state conditions were created by identical liquid hourly meals. IGF-I bioactivity was measured by the kinase receptor activation assay (IGF-I KIRA); total IGF-I was measured by immunoassay. RESULTS: In the fed state, both after AA plus G as well as after G dialysis IGF-I bioactivity increased compared to baseline, while no changes in circulating total IGF-I levels were observed in both treatment arms. However, the increase in IGF-I bioactivity was only significant after AA plus G dialysis (P = 0.02). CONCLUSIONS: Our results provide evidence that in CAPD patients changes in circulating IGF-I bioactivity are associated with nutrient intake and that IGF-I bioactivity rather than total IGF-I is involved in acute responses to nutritional interventions in CAPD patients.

Amino Acid-based peritoneal dialysis solutions for malnutrition: new perspectives.

Protein and energy malnutrition is frequently found in patients on maintenance dialysis and is associated with an increased risk of death. Among a variety of factors involved in the development of protein and energy malnutrition, such as acidosis, insulin resistance, inflammation, and dialysate protein losses, insufficient intake of proteins and energy as a result of anorexia plays a prominent role. Amino acid (AA)-based peritoneal dialysis (PD) solutions can induce an anabolic response in malnourished patients on continuous ambulatory PD if enough calories are ingested simultaneously. Poor appetite, however, may impede the intake of sufficient calories. Peritoneal dialysis solutions containing a mixture of AAs and glucose in a proper ratio can serve as a source of proteins and calories. Such a dialysis solution can be used in fasting patients on nocturnal automated PD as part of a regular dialysis schedule. Using a sophisticated technique involving stable isotopes, this dialysis mixture has been found to induce acute anabolic changes in whole body protein metabolism. Such a metabolic response is similar to that induced by food. Intraperitoneal AAs, in common with ingested proteins, can induce generation of hydrogen ions and urea through oxidation of specific AAs. Supplying AAs together with calories could bring about utilization of AAs for the synthesis of proteins rather than the oxidation of AAs, thereby limiting production of acid and urea. Using dialysis solutions with a buffer concentration of 40 mmol/L further contributes to maintaining acid-base homeostasis. We advocate consideration of usage of AA/glucose dialysate when PD patients cannot comply with dietary requirements. To evaluate the long-term effects of this approach on morbidity and mortality, clinical trials with large groups of patients are needed.

Whole-body protein turnover in peritoneal dialysis patients: a comparison of the [15N]glycine end product and the [13C]leucine precursor methods.

BACKGROUND: Two well-described methods for measuring whole-body protein turnover (WBPT) are the precursor method using a primed continuous infusion of [1-(13)C]leucine and the end-product method with a single oral dose of [(15)N]glycine. We previously measured the effects of amino acid (AA)-containing dialysate on protein anabolism in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using the [1-(13)C]leucine technique. Here, we examine whether the less invasive [(15)N]glycine method could also be appropriate for studying nutritional interventions. METHODS: We compared the results of WBPT measurements using a single oral dose of [(15)N]glycine with those obtained with the primed continuous infusion of [1-(13)C]leucine during AA and glucose (G) dialysis and G-only dialysis in 12 CAPD patients in the fed state. RESULTS: The end-product method showed a wide variation for protein synthesis and breakdown measurements. It did not detect a small but significant increase in protein synthesis with AA-containing dialysate as shown by the precursor method. However, a significant relation was found between both methods for net protein synthesis (i.e. protein synthesis minus breakdown) during AA and G (r = 0.75, P = 0.005) or during G-only dialysis (r = 0.86, P < 0.001). The agreement between the two methods for the net protein balance was good [intra-class correlation coefficient (ICC) = 0.88] with G-only dialysate and moderate (ICC = 0.70) with AA and G dialysate. CONCLUSION: While the precursor method shows less variation, the more convenient end-product method may be useful in larger groups of selected patients including those on PD.

Peritoneal dialysis with solutions containing amino acids plus glucose promotes protein synthesis during oral feeding.

Inadequate food intake plays an important role in the development of malnutrition. Recently, an increased rate of protein anabolism was shown in fasting state in patients who were on automated peritoneal dialysis with combined amino acids (AA) and glucose (G) dialysate serving as a source of both proteins and calories. This study investigated the effects of such a dialysis procedure in the daytime in the fed state in patients who were on continuous ambulatory peritoneal dialysis (CAPD). A crossover study was performed in 12 CAPD patients to compare, at 7-d intervals, a mixture of AA (Nutrineal 1.1%) plus G (Physioneal l.36 to 3.86%) versus G only as control dialysate. Whole-body protein turnover was studied by primed constant intravenous infusion of (13)C-leucine during the 9-h dialysis. For meeting steady-state conditions during whole-body protein turnover, frequent exchanges with a mixture of AA plus G were done using an automated cycler. Fed-state conditions were created by identical liquid hourly meals. Using AA plus G dialysate, as compared with the control, rates of protein synthesis increased significantly (2.02 +/- 0.08 versus 1.94 +/- 0.07 mumol leucine/kg per min [mean +/- SEM]; P = 0.039). Rates of protein breakdown and net protein balance did not differ significantly between AA plus G and G. In conclusion, dialysate that contains AA plus G also improves protein synthesis in fed CAPD patients. The use of such a mixture may contribute to long-term improvement of the nutritional status in malnourished CAPD patients with deficient food intake.

Dialysate as food: combined amino acid and glucose dialysate improves protein anabolism in renal failure patients on automated peritoneal dialysis.

Protein-energy malnutrition as a result of anorexia frequently occurs in dialysis patients. In patients who are on peritoneal dialysis (PD), dialysate that contains amino acids (AA) improves protein anabolism when combined with a sufficient oral intake of calories. It was investigated whether protein anabolism can be obtained with a mixture of AA plus glucose (G) as a source of proteins and calories during nocturnal automated PD (APD). A random-order cross-over study was performed in eight APD patients to compare in two periods of 7 d each AA plus G dialysate obtained by cycler-assisted mixing of one bag of 2.5 L of AA (Nutrineal 1.1%, 27 g of AA) and four bags of 2.5 L of G (Physioneal 1.36 to 3.86%) versus G as control dialysate. Whole-body protein turnover was determined using a primed continuous infusion of L-[1-13C]leucine, and 24-h nitrogen balance studies were performed. During AA plus G dialysis, when compared with control, rates of protein synthesis were 1.20 +/- 0.4 and 1.10 +/- 0.2 micromol/kg per min leucine (mean +/- SD), respectively (NS), and protein breakdown rates were 1.60 +/- 0.5 and 1.72 +/- 0.3 micromol/kg per min (NS). Net protein balance (protein synthesis minus protein breakdown) increased on AA plus G in all patients (mean 0.21 +/- 0.12 micromol leucine/kg per min; P < 0.001). The 24-h nitrogen balance changed by 0.96 +/- 1.21 g/d, from -0.60 +/- 2.38 to 0.35 +/- 3.25 g/d (P = 0.061, NS), improving in six patients. In conclusion, APD with AA plus G dialysate improves protein kinetics. This dialysis procedure may improve the nutritional status in malnourished PD patients.