Chronic peritoneal dialysis (CPD) is widely used and constitutes the dialytic therapy of choice in the management of end-stage renal failure (ESRF) in children1. Since the introduction of CPD into clinical practice, several metabolic problems have arisen2,3,4. In particular, CPD may have contrasting effects on the nutritional status of patients4,5,6,7,8. On the one hand, CPD allows for fewer dietary restrictions than hemodialysis and supplies an extra amount of calories by means of glucose absorbed with the peritoneal fluid. On the other hand, the loss of proteins and amino acids (AAs)5, anorexia related to glucose loading and gastrointestinal disturbances, peritonitis, and possible low-grade inflammatory responses induced by particles and chemicals might cause adverse consequences. Although these factors may engender malnutrition in CPD patients, inadequate intake of proteins and calories appears to be an important cause. Furthermore, serious plasma and muscle AA alterations have been reported in patients on CPD9,10,11,12,13,14.
Adequate protein and energy intakes are essential to the maintenance of nitrogen balance and prevention of malnutrition. While treatment with oral calorie and protein supplements is efficacious, the anorexia associated with chronic renal failure frequently makes this therapeutic approach very difficult to carry out. The use of AA-based dialysis fluid may provide opportunities for compensation of dialytic losses of protein and AA, supplementation of inadequate dietary protein intake, and subsequent improvement in nutritional status, nitrogen balance and plasma and muscle AA in CPD patients.
Several investigators have examined the nutritional benefit of substituting AA for glucose in peritoneal dialysis solutions15,16,17,18,19,20,21,22,23. Some studies have reported a significant improvement in some nutritional parameters, whereas others have shown no significant improvement in the same parameters.
In our experience, a simultaneous supply of calories that is insufficient to allow the absorbed AA to be incorporated into new proteins, thus diverting their use for energy production, may have been the main cause of failure24. Indeed, in almost all of the studies on the use of intraperitoneal AA, a significant increase in serum urea levels is reported, suggesting an unsatisfactory utilization of the infused AA11,16,20,21,22,23,25,26,27,28,29. Moreover, it is well known that without an energy source, nitrogen will not be effectively incorporated into proteins; therefore, in parenteral nutrition, the combined infusion of nonprotein calories and AA has been a key factor in ensuring the best utilization of the AA. Total parenteral nutrition solutions with a nonprotein calorie nitrogen ratio of 150:1 are appropriate for most patients.
The possibility of using peritoneal dialysis itself as a source of nutrients in the treatment of malnutrition is an intriguing concept. Unfortunately, it is not possible to produce CPD bags, which contain both glucose and AA because of such technical problems of preservation as crystallization and caramelization. Hence, the simultaneous infusion of glucose and AA is not possible in continuous ambulatory peritoneal dialysis (CAPD). Conversely, automated peritoneal dialysis (APD), which is based on the use of cyclers, enables different types of solutions to be infused simultaneously. This raises the question of whether APD, using a combined intraperitoneal infusion of AA and glucose, is a valid means of providing an extra amount of readily available nitrogen and calories, and whether an adequate nonprotein calorie/nitrogen ratio could prevent the marked increase in blood urea nitrogen (BUN) usually seen if the AAs are administered without glucose.
METHODS
Subjects
Ten metabolically stable children (seven males and three females, aged 5.5 to 16.5 years) were studied. Pertinent clinical data of the patients and data generated from a standardized peritoneal equilibration test (PET) according to Warady et al are reported in Table 130. The biochemical data are reported in Table 2.
All patients were well established on CPD and had been free of peritonitis for at least two months before the study. None of the patients had any coexisting serious illness, and all had normal liver function tests. The study was approved by the Ethics Committee of the G. Gaslini Institute, and the informed consent was obtained by the parents of the patients.
Dialysis solutions and APD schedule
Two hours after a standard dinner containing 35% of the daily calorie and protein intake, the children received dialysis with an automated cycling machine (Home Choice®; Baxter Healthcare, McGraw Park, IL, USA). The prescribed dialysis solutions were one-quarter glucose 3.86%, one-half glucose 2.27%, and one quarter AA 1.1% (Nutrineal® PD4; Baxter Healthcare, Milan, Italy), thus making up a solution containing 0.275% of AA and 2.1% of glucose. The concentrations of the various constituents are shown in Table 3.
To ascertain the thorough mixing of AA and glucose, we first tested the concentrations of glucose and AA in the solution leaving the mixing bag at each exchange (for eight exchanges) in all of the patients. The mean glucose concentration was 20.84 
0.23 g/L, and the mean AA concentration was 0.271 0.005 g/L. The coefficient of variation in the eight exchanges was 0.052 for glucose and 0.054 for AA.
Bags were weighed before and after APD in order to establish the exact amount of glucose and AA infused. Eight exchanges of 1000 mL m2 body surface area (BSA) were performed with a dwell time of 60 minutes, an infusion time of 10 minutes, and a drainage time of 5 minutes. During the testing period, the patients were not allowed any oral food intake.
The amount of calories provided was calculated as 3.75 calories per gram of anhydrous glucose absorbed. For the calculation of the grams of nitrogen contained in the AA absorbed, it was assumed that 16% of the AA absorbed was nitrogen.
Samples and assay methods
Blood samples were collected before the start of APD and at the beginning of each instillation of peritoneal dialysate for analysis of urea, glucose, insulin, and plasma-free AA. The dialysate effluent was collected at each exchange and the exact volume was recorded; the dialysate was analyzed for urea, glucose and AA levels. Urea and glucose were measured on a Beckman Synchrom CX Autoanalyzer (Beckman Instruments, Fullerton, CA, USA). Insulin was measured by radioimmunoassay (RIA)-coated tubes (Diagnostic Production Corp., Los Angeles, CA, USA). Methods for the plasma sample preparations and the high-pressure liquid chromatography (HPLC) procedure for determining plasma and dialysate free AA have been reported elsewhere31,32.
Statistical analysis
Statistical analysis was performed using the Student paired t test. Pearson's coefficient of correlation (r) was used to calculate the correlations. P < 0.05 was regarded as a significant difference.
RESULTS
Automated peritoneal dialysis with a combined infusion of AA and glucose was well tolerated by all patients, and no side effects were observed.
The amount of AA infused during the APD was 20.0 4.0 g/m2 BSA, and the absorbed amount was 10.9 3.5 g/m2 BSA (55.2 + 13.2%). The amount of glucose infused was 152.8 30.6 g/m2 BSA, of which 53.1 24.6 g/m2 BSA was absorbed (33.7 10.0%). The percentage of absorption of AA and glucose gives a ratio of nonprotein calories to nitrogen of 115.4:1.
No significant correlation was found between the dialysate/plasma (D/P) ratio for creatinine and glucose at two and four hours and the glucose and AA absorption during the test. The mean ultrafiltration was 0.76 0.52 L/m2 BSA.
Table 4 reports the absorption in percentage and g/m2 BSA of glucose and AA at every exchange and the BUN, glucose, and insulin blood levels measured at every exchange. The glucose and AA absorption did not show significant differences in the eight exchanges ranging from 30.9 11.8% to 35 14.8% of the infused amount for glucose and from 49.6 13% to 55.1 17.3% for AA.
Table 4 - Percent amino acids and glucose absorption and blood urea nitrogen, glucose and insulin levels at start of automated peritoneal dialysis (APD) and at every exchange.
Full table Blood urea nitrogen levels showed a slight but significant decrease from the second (66 14 mg/dL) to the eighth exchange (56.9 13.1 mg/dL).
Glucose plasma levels did not show significant differences during the eight exchanges ranging from 85.1 32 mg/dL to 96.8 39.2 mg/dL.
The insulin plasma values that were higher than normal (22.8 9 IU/mL) at the start of APD, because of the physiological postprandial increase, showed a significant decrease to normal values after the fourth exchange (15.4 9 IU/mL) and further declined from the fourth to the eighth exchange.
Plasma AA levels during the study period are reported in Table 5. Among the essential AAs, which were contained in the 1.1% AA solution, histidine and isoleucine concentrations did not show significant variations during the eight exchanges. Leucine plasma concentrations were reduced at the sixth exchange, and lysine plasma concentrations were significantly reduced only at the fifth exchange. Phenylalanine levels were significantly reduced at the sixth and seventh exchange, and tyrosine levels were significantly lower from the fourth to the eighth exchange. Valine concentrations were significantly higher from the first to the seventh exchange. Methionine levels showed a significant rise from the first to the fourth and at the seventh exchange, and threonine levels were significantly raised only at the second exchange.
mol/L) at start of APD and at every exchange.Among the nonessential AA, those contained in the 1.1% AA solution, namely arginine, glycine, serine, and alanine, did not show significant variations in plasma concentrations during the eight exchanges, except for a significant decrease of glycine plasma levels at the first exchange. Among the nonessential AA not contained in the 1.1% AA solution, asparagine levels showed a significant decrease from the first to the eighth exchange. Glutamine levels were significantly reduced at the second and from the fifth to the eighth exchange. Ornithine concentrations were significantly lower from the fifth to the seventh exchange. Citrulline plasma concentrations were significantly higher from the first to the eighth exchange, and aspartic and glutamic acid showed a significant rise, respectively, at the fourth and at the eighth exchange.
DISCUSSION
The results of this study indicate that the simultaneous infusion of glucose and AA into peritoneum is safe and does not induce side effects. This finding corroborates reports by Honda et al, who evaluated the acute effects of the short-term use of a mixed solution of glucose and essential AA in children on CAPD33.
The absence of a significant correlation between the D/P ratio for creatinine and glucose at two and four hours and the glucose and AA absorption during the test should be explained, at least in part, by the shorter dwell time of the exchanges performed during the APD treatment (60 minutes).
Both insulin and AA are necessary for the stimulation of protein anabolism34,35. Net protein deposition in body tissues can be achieved by the suppression of endogenous protein degradation, by the stimulation of protein synthesis, or by both. A number of in vitro studies have demonstrated that insulin inhibits protein degradation in the liver36 and muscle37. Moreover, while it stimulates protein synthesis in muscle38, it does not seem to have any such effect in the liver36. In addition, AAs have been shown to stimulate protein synthesis directly in muscle39 and suppress proteolysis in perfused rat liver40. Thus, both insulin and AA can directly stimulate protein anabolism in vitro. A number of in vivo studies show that hyperinsulinemia decreases proteolysis and oxidation of essential AA41,42,43.
Leucine kinetic data reveal that hyperinsulinemia and hyperaminoacidemia stimulate net protein anabolism by different mechanisms. Hyperinsulinemia decreases proteolysis but does not stimulate leucine incorporation into proteins, while hyperaminoacidemia per se stimulated the incorporation of leucine in proteins but did not suppress endogenous proteolysis. When combined, they have a cumulative effect on leucine deposition into body proteins44.
A recent preliminary report indicates that peritoneal dialysis causes concurrent acute anabolic and catabolic effects on muscle protein dynamics. The glucose-induced increase in insulin levels is followed by an inhibition of muscle protein degradation. However, this anabolic effect is blunted by a decrease in muscle protein synthesis, which is probably the consequence of a decrease in the supply of selected AAs (valine, leucine, isoleucine, and tyrosine) and potassium to muscle. The final effect on muscle protein balance may vary depending on which of these two opposing factors—insulin versus reduced substrate availability—predominates (abstract; Garibotto et al, J Am Soc Nephrol 9:282A, 1998).
In our study, both stimulatory effects were present. The insulin levels were already high at the beginning of APD because of the postprandial increase and returned to normal only three hours after the beginning of APD. The free AA plasma levels were also already increased two hours after dinner and remained high for the entire APD treatment because of the continuous absorption of AA from the peritoneum. On account of the specific composition of the AA solution, the plasma levels of selected AA with a key role in muscle protein synthesis, namely valine, leucine, isoleucine, and tyrosine, showed persistently high levels during the study period. No marked increases in arginine levels, which can result in an excessive production of nitrogen oxide, were observed.
Several investigators have examined the nutritional benefit of substituting AAs for glucose in peritoneal dialysis solutions15,16,17,18,19,20,21,22,23,25,26,27,28,33,45,46. These studies vary in length and in the AA formulation used; in some studies, the patients selected were not malnourished, and in general, these studies were conducted on a small number of patients. This may account to some extent for the diversity in the results.
Nearly all of the studies on the use of intraperitoneal AA report a significant increase in serum urea levels, suggesting a nonoptimal utilization of the infused AA15,20,21,22,23,25,26,27,28. Furthermore, in a short-term study on the use of AA in CAPD, Goodship et al found that blood glucose rose to significantly higher levels during the 1.36% glucose exchange, but that the increase in serum insulin was significantly greater with the 1% AA solution, suggesting that many of the intraperitoneally absorbed AAs may be converted to glucose16.
Like AA, nitrogen will not be efficiently incorporated into protein without any other energy source, chiefly because of the energy dissipated as heat during their metabolism (specific dynamic action), which is especially high for protein. Moreover, incorporation of AA into peptides requires three high-energy phosphate bonds, thereby using 10 kCal per mole derived from the hydrolysis of adenosine 5'-triphosphate (ATP). Any excess of dietary energy over basic needs improves the efficiency of dietary nitrogen utilization47. A recent report shows that the ingestion of a carbohydrate-lipid meal during a CAPD cycle dialysis with a 1.1% AA solution inhibits protein breakdown and reinforces a positive effect of the AA solution on protein balance48.
In parenteral nutrition, the combined uptake of nonprotein calories and AA has been a key factor in ensuring the optimal utilization of the AA. Total parenteral nutrition solutions with a nonprotein calorie-nitrogen ratio of 150:1 are considered appropriate for most patients to incorporate delivered AA into new proteins. The percentages of absorption of AA and glucose give a ratio of nonprotein calories to nitrogen of 115.4:1, which is close to the previously mentioned ratio of 150:1. Furthermore, plasma urea levels did not change during the study period, suggesting that the absorbed AAs were incorporated into new proteins.
By this procedure, it is possible to achieve three favorable conditions simultaneously for protein synthesis: hyperinsulinemia, hyperaminoacidemia, and an adequate nonprotein calorie/nitrogen ratio of the absorbed glucose and AA.
It therefore follows that there is a sound theoretical basis for the use of this procedure, since it could facilitate the incorporation of infused AAs into new proteins. Using a combined glucose and AA containing peritoneal dialysis solution for one year, Brem et al reported improvements in growth, serum albumin, and appetite in a child on continuous cycling peritoneal dialysis (CCPD), without significant changes in BUN levels and side effects49. The long-term use of such a technique could therefore improve the nutritional status of children on peritoneal dialysis, as already reported in a preliminary study (abstract; Canepa et al, J Am Soc Nephrol 7:1441, 1996).
References
| 1. | Warady BA, Hebert D & Sullivan EK et al. Renal transplantation, chronic dialysis, and chronic renal insufficiency in children and adolescents: The 1995 Annual Report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol 1997; 11: 49–64 10.1007/s004670050232. | Article | PubMed | ISI | ChemPort | |
| 2. | Gokal R, Ramos JM & McGurk JG et al. Hyperlipidemia in patients on continuous ambulatory peritoneal dialysis. inAdvances in Peritoneal Dialysis 1981; edited by Gahl GM, Kessel M, Nolph KD Amsterdam, Excerpta Medica pp 430–435. |
| 3. | Stefanidis CJ, Hewitt IK & Balfe JW. Growth in children receiving continuous ambulatory peritoneal dialysis. J Pediatr 1983; 102: 681–685. | PubMed | ISI | ChemPort | |
| 4. | Salusky IB, Fine RN & Nelson D et al. Nutritional status of children undergoing continuous ambulatory peritoneal dialysis. Am J Clin Nutr 1983; 38: 599–611. | PubMed | ISI | ChemPort | |
| 5. | Giordano C, De Santo NG & Capodicasa G et al. Amino acids losses during CAPD. Clin Nephrol 1980; 14: 230–232. | PubMed | ISI | ChemPort | |
| 6. | Grodstein GP, Blumenkrantz MJ & Kopple JD et al. Glucose absorption during continuous ambulatory peritoneal dialysis. Kidney Int 1981; 19: 564–567. | PubMed | ISI | ChemPort | |
| 7. | Broyer M, Niaudet P & Champion G et al. Nutritional and metabolic studies in children on continuous ambulatory peritoneal dialysis. Kidney Int 1983; 24 Suppl 15: S106–S110. | ISI | |
| 8. | Canepa A, Perfumo F & Carrea A et al. Nutritional status in children receiving chronic peritoneal dialysis. Perit Dial Int 1996; 16 Suppl 1: S526–S531. | PubMed | |
| 9. | Randerson DH, Chapman GV & Farrel PC. Amino acid and dietary status in CAPD patients. inPeritoneal Dialysis 1981; edited by Atkins R, Thomson N, Farrel P Edinburgh, Churchill Livingstone pp 179–185. |
| 10. | Bergström J, Furst P & Noree LO. Intracellular free amino acids in muscle tissue of patients with chronic uremia: The effect of peritoneal dialysis and infusion of essential amino acids. Clin Sci Mol Med 1978; 54: 51–60. | PubMed | |
| 11. | Canepa A, Perfumo F & Carrea A et al. Long term effect of amino acid dialysis solution in children on continuous ambulatory peritoneal dialysis. Pediatr Nephrol 1991; 5: 215–219. | Article | PubMed | ISI | ChemPort | |
| 12. | Lindholm B, Alvestrand A, Furst P & Bergström J. Plasma and muscle free aminoacids during continuous ambulatory peritoneal dialysis. Kidney Int 1986; 35: 1219–1226. |
| 13. | Graziani G, Cantaluppi A & Casati S et al. Branched chain and aromatic free amino acids in plasma and skeletal muscle of uremic patients undergoing hemodialysis and CAPD. Int J Artif Organ 1984; 7: 85–88. | ISI | ChemPort | |
| 14. | Canepa A, Divino Filho JC & Forsberg AM et al. Children on continuous ambulatorial peritoneal dialysis: Muscle and plasma proteins, aminoacids and nutritional status. Clin Nephrol 1996; 46: 125–131. | PubMed | ISI | ChemPort | |
| 15. | Young GA, Dibbie JB & Hobson SM et al. The use of an amino acid-based CAPD fluid over 12 weeks. Nephrol Dial Transplant 1989; 4: 285–292. | PubMed | ISI | ChemPort | |
| 16. | Goodship TH, Lloyd S & Mckenzie PW et al. Short-term studies of the use of aminoacids as an osmotic agent in continuous ambulatory peritoneal dialysis. Clin Sci 1987; 73: 471–478. | PubMed | ISI | ChemPort | |
| 17. | Haming RM, Balfe JW & Zlottin SH. Effectiveness and nutritional consequences of amino acid-based vs. glucose-based dialysis solutions in infants and children receiving CAPD. Am J Clin Nutr 1987; 46: 22–30. | PubMed | |
| 18. | Canepa A, Perfumo F & Carrea A et al. Continuous ambulatory peritoneal dialysis (CAPD) of children with amino acid solution: Technical and metabolic aspects. Perit Dial Int 1990; 10: 215–220. | PubMed | ISI | ChemPort | |
| 19. | Lindholm B, Weryenski A & Bergström J. Peritonel dialysis with amino acid solution: Fluid and solute transport kinetics. Artif Organs 1988; 12: 2–10. | PubMed | ISI | ChemPort | |
| 20. | Bruno M, Bagnis C & Marangella M et al. CAPD with amino acid dialysis solution: A long-term cross-over study. Kidney Int 1989; 35: 1189–1194. | PubMed | ISI | ChemPort | |
| 21. | Scanziani R, Dozio B & Ioenitti G. Use of amino acids in CAPD in diabetics. inAdvances in Peritoneal Dialysis (vol 6) 1990; edited by Khanna R, Nolph KD, Prowant BF, Oreopoulos DG Toronto, University Press pp 53–55. |
| 22. | Kopple JD, Bernard D & Messana J et al. Treatment of malnourished CAPD patient with an amino acid based dialysate. Kidney Int 1995; 47: 1148–1157. | PubMed | ISI | ChemPort | |
| 23. | Faller B, Aparicio M & Faict D et al. Clinical evaluation of an optimised 1.1% amino acid solution for peritoneal dialysis. Nephrol Dial Transplant 1995; 10: 1432–1437. | PubMed | ISI | ChemPort | |
| 24. | CANEPA A, PERFUMO F & CARREA A et al. Protein and caloric intake nitrogen losses and nitrogen balance in children undergoing chronic peritoneal dialysis,. inAdvances in Peritoneal Dialysis 1996; vol 12 edited by KHANNA R, NOLPH KD, OREOPOULOS DG, et al Toronto, University Press pp: 326–329. |
| 25. | Oren A, Wu G & Anderson GH et al. Effective use of amino acid dialysate over four weeks in CAPD patients. Perit Dial Bull 1983; 3: 66–73. | ISI | |
| 26. | Pedrsen FB, Dragsholt C, Laier E & Frifelt JJ. Alternate use of amino acid and glucose solutions in CAPD. Perit Dial Bull 1985; 5: 215–218. |
| 27. | Dombros N, Prutis K & Tong M et al. Six month overnight intraperitoneal amino acid infusion in continuous ambulatory peritoneal dialysis (CAPD) patients: No effect on nutritional status. Perit Dial Int 1990; 10: 79–84. | PubMed | ISI | ChemPort | |
| 28. | Arfeen S, Goodship TH, Kirkwood A & Ward MK. The nutritional/metabolic and hormonal effects of 8 weeks of continuous ambulatory peritoneal dialysis with a 1% amino acid solution. Clin Nephrol 1990; 33: 192–199. | PubMed | ISI | ChemPort | |
| 29. | Rubin J & Garner T. Positive nitrogen balance after intraperitoneal administration of aminoacids in 3 patients. Perit Dial Int 1994; 14: 223–226. | PubMed | ISI | ChemPort | |
| 30. | Warady BA, Alexander SR & Hossli S et al. Peritoneal membrane transport function in children receiving long-term dialysis. J Am Soc Nephrol 1996; 7: 2385–2391. | PubMed | ISI | ChemPort | |
| 31. | Qureshi AG, Fohlin L & Bergström J. Application of high performance liquid chromatography to the determination of free amino acids in physiological fluids. J Chromatogr 1984; 297: 91–100. | PubMed | ISI | |
| 32. | Canepa A, Perfumo F & Carrea A et al. Measurement of free amino acids in polymorphonuclear granulocytes by high performance liquid chromatography. J Chromatogr 1989; 491: 200–208. | PubMed | ISI | ChemPort | |
| 33. | Honda M, Kamiyama Y & Hasegawa O et al. Effect of short-term essential amino acid containing dialysate in young children on CAPD. Perit Dial Int 1991; 11: 76–80. | PubMed | ISI | ChemPort | |
| 34. | Cahill G. Physiology of insulin in man. Diabetes 1971; 20: 785–798. | PubMed | ISI | ChemPort | |
| 35. | Greenberg GR, Marliss EB & Anderson GH et al. Protein-sparing therapy in postoperative patients: Effects of added hypocaloric glucose or lipid. N Engl J Med 1976; 294: 1411–1416. | PubMed | ISI | ChemPort | |
| 36. | Mortimore GE & Mondon CE. Inhibition by insulin of valine turnover in liver. J Biol Chem 1970; 245: 2375–2383. | PubMed | ISI | ChemPort | |
| 37. | Jefferson LS, Li JB & Rannels SR. Regulation by insulin of amino acid release and protein turnover in the perfused rat hemicorpus. J Biol Chem 1977; 252: 1476–1483. | PubMed | ISI | ChemPort | |
| 38. | Hutson SM, Zapalowsky C, Cree TC & Harper AE. Regulation of leucine and  -ketoisocaproic acid metabolism in skeletal muscle: Effects of stravation and insulin. J Biol Chem 1980; 255: 2418–2426. | PubMed | ISI | ChemPort | |
| 39. | Morgan HE, Earl DCN & Broadus A et al. Regulation of protein synthesis in heart muscle. I. Effect of amino acid levels on protein synthesis. J Biol Chem 1971; 246: 2152–2162. | PubMed | ISI | ChemPort | |
| 40. | Woodside KH & Mortimore GE. Suppression of protein turn over by amino acids in the perfused liver. J Biol Chem 1972; 247: 6474–6481. | PubMed | ISI | ChemPort | |
| 41. | Abumrad NN, Jefferson LS & Rannels SR et al. Role of insulin in the regulation of leucine kinetics in the conscious dog. J Clin Invest 1982; 70: 1031–1041. | PubMed | ISI | ChemPort | |
| 42. | Tessari P, Nosedini R & Trevisan R et al. Defective suppression by insulin of leucine and -ketoisocaproate metabolism in insulin-dependent, type I diabetes. J Clin Invest 1986; 77: 1797–1804. | PubMed | ISI | ChemPort | |
| 43. | Fugakawa NK, Minaker KL & Rowe JW et al. Insulin-mediated reduction of whole-body protein breakdown: Dose-response effects on leucine metabolism. J Clin Invest 1986; 76: 2300–2311. |
| 44. | Tessari P, Inchiostro S & Biolo G et al. Differential effects of hyperinsulinemia and hyperacidemia on leucine-carbon metabolism in vivo. J Clin Invest 1987; 79: 1062–1069. | PubMed | ISI | ChemPort | |
| 45. | Qamar IU, Levin L & Balfe JW et al. Effects of 3 month amino acid dialysis compared to dextrose dialysis in children on continuous ambulatory peritoneal dialysis. Perit Dial Int 1994; 14: 34–41. | PubMed | ISI | ChemPort | |
| 46. | De Bisschop E, Allein S & Van Der Niepen P et al. Effect of amino acid administration on uremic muscle metabolism: A 31P-spectroscopy study. Kidney Int 1997; 51: 1182–1187. | PubMed | ChemPort | |
| 47. | Scrimshaw NS. An analysis of past and present recommended dietary allowances for protein in health and disease. N Engl J Med 1976; 294: 198–203. | PubMed | ISI | ChemPort | |
| 48. | Delarue J, Maingourd C & Objois M et al. Effects of an amino acid dialysate on leucine metabolism in continuous ambulatory peritoneal dialysis patients. Kidney Int 1999; 56: 1934–1943 10.1046/j.1523-1755.1999.00723.x. | Article | PubMed | ISI | ChemPort | |
| 49. | Brem AS, Maaz D, Shemin DG & Wolfson M. Use of amino acid peritoneal dialysate for one year in a child on CCPD. Perit Dial Int 1996; 16: 634–641. | PubMed | ISI | ChemPort | |
Acknowledgments
This work was supported by the Baxter Healthcare Corporation, Renal Division (Extramural Grant Program). This work was presented in part at the annual meeting of the American Society of Nephrology (Orlando, FL, USA), October 1994, and at the International Society of Peritoneal Dialysis, Seoul, South Korea, August 1998. The authors gratefully thank Professor Jonas Bergström for comments and suggestions.
