FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2016838197> ?p ?o ?g. }

• W2016838197 endingPage "369" @default.
• W2016838197 startingPage "364" @default.
• W2016838197 abstract "Patients with peritoneal dialysis are at risk for malnutrition and hypoalbuminemia, which are indicators of poor outcome. Recently, it was shown that dialysis solutions containing amino acids (AAs) and glucose improve protein anabolism in peritoneal dialysis patients. We determined if the same solutions could increase the fractional synthesis rate of albumin along with whole-body protein synthesis. Changes in the fractional albumin synthetic rate reflect acute change in hepatic albumin synthesis. A random-order cross-over study compared the effects of Nutrineal® (AA source) plus Physioneal® (glucose) dialysate with Physioneal® alone dialysate. Eight patients in the overnight fasting state were compared to 12 patients in the daytime-fed state. Fractional albumin synthetic rate and whole-body protein synthesis were determined simultaneously using a primed-continuous infusion of L-[1-13C]-leucine. Fractional albumin synthesis on AAs plus glucose dialysis did not differ significantly from that on glucose alone in the fasting or the fed state. Protein intake by itself (fed versus fasting) failed to induce a significant increase in the fractional synthetic rate of albumin. Conversely, the oral protein brought about a significant stimulation of whole-body protein synthesis. Our findings show that the supply of AAs has different effects on whole-body protein synthesis and the fractional synthetic rate of albumin. Patients with peritoneal dialysis are at risk for malnutrition and hypoalbuminemia, which are indicators of poor outcome. Recently, it was shown that dialysis solutions containing amino acids (AAs) and glucose improve protein anabolism in peritoneal dialysis patients. We determined if the same solutions could increase the fractional synthesis rate of albumin along with whole-body protein synthesis. Changes in the fractional albumin synthetic rate reflect acute change in hepatic albumin synthesis. A random-order cross-over study compared the effects of Nutrineal® (AA source) plus Physioneal® (glucose) dialysate with Physioneal® alone dialysate. Eight patients in the overnight fasting state were compared to 12 patients in the daytime-fed state. Fractional albumin synthetic rate and whole-body protein synthesis were determined simultaneously using a primed-continuous infusion of L-[1-13C]-leucine. Fractional albumin synthesis on AAs plus glucose dialysis did not differ significantly from that on glucose alone in the fasting or the fed state. Protein intake by itself (fed versus fasting) failed to induce a significant increase in the fractional synthetic rate of albumin. Conversely, the oral protein brought about a significant stimulation of whole-body protein synthesis. Our findings show that the supply of AAs has different effects on whole-body protein synthesis and the fractional synthetic rate of albumin. Hypoalbuminemia has been recognized as a strong predictor of increased risk of morbidity and mortality in peritoneal dialysis patients.1Kaysen G.A. Biological basis of hypoalbuminemia in ESRD.J Am Soc Nephrol. 1998; 9: 2368-2376PubMed Google Scholar, 2Blake P.G. Flowerdew G. Blake R.M. et al.Serum albumin in patients on continuous ambulatory peritoneal dialysis – predictors and correlations with outcomes.J Am Soc Nephrol. 1993; 3: 1501-1507PubMed Google Scholar, 3Spiegel D.M. Breyer J.A. Serum albumin: a predictor of long-term outcome in peritoneal dialysis patients.Am J Kidney Dis. 1994; 23: 283-285Abstract Full Text PDF PubMed Scopus (69) Google Scholar Because in protein-energy malnutrition albumin synthesis is reduced, hypoalbuminemia traditionally has been attributed to poor nutritional intake.4Kopple J.D. Effect of nutrition on morbidity and mortality in maintenance dialysis patients.Am J Kidney Dis. 1994; 24: 1002-1009Abstract Full Text PDF PubMed Scopus (233) Google Scholar In terms of kinetics, plasma albumin level is determined by the synthetic rate, the catabolic rate plus external losses, and volume of distribution of albumin. Various clinical conditions apart from protein-energy malnutrition affect its concentrations including inflammatory states, volume expansion, and increased losses of albumin.5Yeun J.Y. Kaysen G.A. Factors influencing serum albumin in dialysis patients.Am J Kidney Dis. 1998; 32: S118-S125Abstract Full Text PDF PubMed Google Scholar, 6Kaysen G.A. Schoenfeld P.Y. Albumin homeostasis in patients undergoing continuous ambulatory peritoneal dialysis.Kidney Int. 1984; 25: 107-114Abstract Full Text PDF PubMed Scopus (139) Google Scholar, 7Blumenkrantz M.J. Gahl G.M. Kopple J.D. et al.Protein losses during peritoneal dialysis.Kidney Int. 1981; 19: 593-602Abstract Full Text PDF PubMed Scopus (226) Google Scholar, 8Prinsen B.H.C.M.T. Rabelink T.J. Beutler J.J. et al.Increased albumin and fibrinogen synthesis rate in patients with chronic renal failure.Kidney Int. 2003; 64: 1495-1504Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar, 9Kalantar-Zadeh K. Block G. McAllister C.J. et al.Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients.Am J Clin Nutr. 2004; 80: 299-307PubMed Google Scholar In PD patients, considerable amounts of albumin are lost via dialysate. Plasma albumin concentration has been found to be a poor marker of protein-energy malnutrition.10Jones C.H. Newstead C.G. Will E.J. et al.Assessment of nutritional status in CAPD patients: serum albumin is not a useful measure.Nephrol Dia Transplant. 1997; 12: 1406-1413Crossref PubMed Scopus (88) Google Scholar Most of the studies evaluating the acute effects of nutritional intervention in patients treated with PD, could not demonstrate appreciable alterations in the serum albumin concentration.11Karlawish J. Craiq R.M. Koretz R. The effect of total parenteral nutrition on serum albumin.J Clin Gastroenterol. 1994; 19: 300-302Crossref PubMed Scopus (12) Google Scholar Recently, we found a stimulation of protein synthesis in PD patients in the fasting and fed state with dialysate containing a mixture of amino acids (AAs) plus glucose (G).12Tjiong H.L. Van den Berg J.W. Wattimena J.L. et al.Dialysate as food: combined amino acid and glucose dialysate improves protein anabolism in renal failure patients on automated peritoneal dialysis.J Am Soc Nephrol. 2005; 16: 1486-1493Crossref PubMed Scopus (85) Google Scholar,13Tjiong H.L. Rietveld T. Wattimena J.L. et al.Peritoneal dialysis with solutions containing amino acids plus glucose promotes protein synthesis during oral feeding.Clin J Am Soc Nephrol. 2007; 2: 74-80Crossref PubMed Scopus (36) Google Scholar Improvements in whole-body protein synthesis by supply of AA may be, partly, due to an increase in the fractional synthesis rate of albumin (FSR-albumin). Alterations in the FSR-albumin represent acute changes in hepatic albumin synthesis. In this study, we analyzed in PD patients whether combined AA plus G dialysate could increase FSR-albumin in PD patients both during the night in the fasting state as well as during the day in the fed state. Moreover, by comparing the fasting and fed state, we aimed to study the effects of food per se. Using stable isotope infusion technique, the FSR-albumin was measured simultaneously with the whole-body protein synthesis (WBPS). The liquid food contained on average 0.96±s.d. 0.2 g protein/kg/day and 22±s.d. 5.0 kcal/kg/day, that was consumed completely and was well tolerated in all patients. In the night-time fasting and daytime-fed study, baseline serum C-reactive protein levels ranged from 1 to 33 mg/l (median 9.5 mg/l) and from 1 to 40 mg/l (median 6.0 mg/l), respectively. Baseline serum albumin was 38±3.0 and 38±2.0 g/l, respectively. Baseline levels of serum bicarbonate in the fasting- and fed-state study were 22.8±2.2 and 23.7±3.3 mmol/l, respectively. As shown in Table 1 in the night-time fasting-state study, FSR-albumin with AA plus G dialysate was not significantly increased as compared with G only dialysate (mean difference: 1.0±s.e. 0.7%/day, P=0.18). In the daytime-fed state study, FSR-alb was higher using AA plus G dialysate than with G only dialysate, but again, not statistically significant (mean difference: 0.6±s.e. 0.4 %/day, P=0.17). FSR-albumin during G dialysis in the fed state was also not significantly higher than that in the fasting state (12.0±s.e. 0.5 versus 10.3±s.e. 0.9%/day, respectively, mean difference 1.7±s.e. 0.9, P=0.07).Table 1Albumin kineticsAAG dialysateG dialysateFSR-albumin %/dayFSR-albumin %/dayFasting patients (N=8) 111.4310.40 28.119.71 316.2213.21 412.4610.23 59.647.33 69.347.44 711.319.99 812.0014.18 Mean±s.d.11.37±2.5110.25±2.53Fed patients (N=12) 111.4612.26 213.4012.41 312.9112.19 49.529.92 511.8312.28 611.5812.14 79.329.74 814.2114.82 916.4114.25 1012.5310.08 1115.4312.11 1212.8912.11 Mean±s.d.12.62±2.1112.03±1.55AAG, amino-acid plus glucose; G, glucose; FSR, fractional synthesis rate of albumin. Open table in a new tab AAG, amino-acid plus glucose; G, glucose; FSR, fractional synthesis rate of albumin. WBPS was significantly higher in the fed state compared with the fasting state, both for AA plus G and G only containing solutions (Figure 1). Baseline serum insulin in the fasting-state study was 32.1±9.9 mU/l. In the fed-state study, serum insulin levels increased significantly with either AA plus G dialysate (22±13 mU/l versus 73±45 mU/l, P<0.001) or G dialysate (18±11 mU/l versus 62±35 mU/l, P=0.001) when compared with baseline values. There were no significant differences in insulin levels between the AA plus G and G only dialysis as reported previously.13Tjiong H.L. Rietveld T. Wattimena J.L. et al.Peritoneal dialysis with solutions containing amino acids plus glucose promotes protein synthesis during oral feeding.Clin J Am Soc Nephrol. 2007; 2: 74-80Crossref PubMed Scopus (36) Google Scholar As shown in Table 2, plasma AA levels and in particular the essential AAs increased significantly during AA plus G dialysis compared with G only dialysis.Table 2Plasma AAs during AAG and G dialysis in the fasting- and fed-sate studyaData are expressed as mean±s.d. in μmol/l.Overnight fasting stateDaytime-fed stateAAG dialysisG dialysisAAG dialysisG dialysisEssential Threonine177±38**121±28194±30**167±28 Valine240±41**125±22357±72**260 ±55 Methionine18±8*9±860±15**37±14 Isoleucine85±19**56±13110±24**90±21 Leucine132±23**110±23198±41**172±37 Phenylalanine76±12**66±10113±24**93±24 Lysine174±31**155±37197±27184±33 Histidine94±10**72±1085±15**77±15 Total essentialbCalculated as the sum of threonine, valine, methionine, isoleucine, leucine, phenylalanine, lysine, and histidine.995±141**715±1291314±144**1080±152Semiessential Tyrosine41±939±996±22*89±22 CystineNDND14±1111±7Nonessential Taurine43±1345±2030±1235±27 Aspartic acidNDND37±731±14 Asparagine39±1036±970±1375±15 Serine107±4876±1590±1889±19 Glutamic acid286±112284±11693±5590±48 Glutamine260±107224±95475±57481±64 Glycine382±116*328±104254±70260±66 Alanine413±95*354±93542±91*500±107 Citrulline105±28**90±3090±2790±22 Ornithine61±13**49±1570±11**60±12 Arginine127±29**101±2994±16*84±14 Proline290±43**240±42622±117*574±112 Total nonessentialcCalculated as the sum of taurine, aspartic acid, asparagine, serine, glutamic acid, glutamine, glycine, alanine, citrulline, ornithine, arginine, and proline.2111±233**1827±2392465±243*2369±254 Total AAsdCalculated as the sum of total essential AAs and total nonessential AAs with tyrosine (overnight fasting-state study) and with cystine and tyrosine (daytime-fed state study).3148±344**2581±3563890±349**3550±381AA, amino acid; AAG, amino acid and glucose; G, glucose; ND, not determined.*P<0.05 versus G dialysis; **P<0.01 versus G dialysis.a Data are expressed as mean±s.d. in μmol/l.b Calculated as the sum of threonine, valine, methionine, isoleucine, leucine, phenylalanine, lysine, and histidine.c Calculated as the sum of taurine, aspartic acid, asparagine, serine, glutamic acid, glutamine, glycine, alanine, citrulline, ornithine, arginine, and proline.d Calculated as the sum of total essential AAs and total nonessential AAs with tyrosine (overnight fasting-state study) and with cystine and tyrosine (daytime-fed state study). Open table in a new tab AA, amino acid; AAG, amino acid and glucose; G, glucose; ND, not determined. *P<0.05 versus G dialysis; **P<0.01 versus G dialysis. Recently, we showed an acute anabolic effect of AA plus G-based dialysis solutions in PD patients in the fasting and fed state.12Tjiong H.L. Van den Berg J.W. Wattimena J.L. et al.Dialysate as food: combined amino acid and glucose dialysate improves protein anabolism in renal failure patients on automated peritoneal dialysis.J Am Soc Nephrol. 2005; 16: 1486-1493Crossref PubMed Scopus (85) Google Scholar,13Tjiong H.L. Rietveld T. Wattimena J.L. et al.Peritoneal dialysis with solutions containing amino acids plus glucose promotes protein synthesis during oral feeding.Clin J Am Soc Nephrol. 2007; 2: 74-80Crossref PubMed Scopus (36) Google Scholar In this study, we investigated the influence of such dialysis solutions on the FSR-albumin in PD patients. We found that FSR-albumin values were similar to those obtained in one previous study in Continuous Ambulatory Peritoneal Dialysis patients.8Prinsen B.H.C.M.T. Rabelink T.J. Beutler J.J. et al.Increased albumin and fibrinogen synthesis rate in patients with chronic renal failure.Kidney Int. 2003; 64: 1495-1504Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar We did not find a statistically significant increase in FSR-albumin with combined AA plus G dialysate compared to G only dialysate in either the fasting or in the fed state. In contrast, in several reported experimental and human studies, it was found that albumin synthesis increased in response to proteins or AA supplementation.14Hunter K.A. Ballmer P.E. Anderson S.E. et al.Acute stimulation of albumin synthesis rate with oral meal feeding in healthy subjects measured with [ring-2H5]phenylalanine.Clin Sci. 1995; 88: 235-242Crossref PubMed Scopus (65) Google Scholar,15De Feo P. Horber F.F. Haymond M.W. Meal stimulation of albumin synthesis: a significant contributor to whole body protein synthesis in humans.Am J Physiol. 1992; 263: E794-E799PubMed Google Scholar In a recent study in seven hemodialysis patients, FSR-albumin increased in response to Intra Dialytic Parenteral Nutrition.16Pupim L.B. Flakoll P.J. Ikizler T.A. Nutritional supplementation acutely increases albumin fractional synthetic rate in chronic hemodialysis patients.J Am Soc Nephrol. 2004; 15: 1920-1926Crossref PubMed Scopus (62) Google Scholar In this study, 11 g of AA were given per hour of dialysis time. In our studies, about 3 g of AA per hour of dialysis were administered. Taking into account that about 40–50% of the supplied AA was absorbed, 1.6 g AA per hour of dialysis was given. In our study, the failure to demonstrate a significant effect on FSR-albumin may be due to the low amount of AA given. However, even an oral protein intake of 8 g per hour on average did not bring about a statistically significant increase in FSR-albumin, as shown when the corresponding results of the fasting- and the fed-state study are compared. When comparing fasting and fed state in PD patients, it is important to realize that a moderate hyperinsulinemia is present even in fasting PD patients through the continuous flow of glucose via dialysis solutions.17Garibotto G. Sofia A. Canepa A. et al.Acute effects of peritoneal dialysis with dialysates containing dextrose or dextrose and amino acids on muscle protein turnover in patients with chronic renal failure.J Am Soc Nephrol. 2001; 12: 557-567PubMed Google Scholar Various experimental and human studies provide ample evidence that in addition to substrate availability, insulin has a stimulating effect on hepatic albumin synthesis.18De Feo P. Gaisano M.G. Haymond M.W. Differential effects of insulin deficiency on albumin and fibrinogen synthesis in humans.J Clin Invest. 1991; 88: 833-840Crossref PubMed Google Scholar, 19Flaim K.E. Hutson S.M. Lloyd C.E. et al.Direct effect of insulin on albumin gene expression in primary cultures of rat hepatocytes.Am J Physiol. 1985; 249: E447-E453PubMed Google Scholar, 20Volpi E. Lucidi P. Cruciani G. et al.Contribution of amino acids and insulin to protein anabolism during meal absorption.Diabetes. 1996; 45: 1245-1252Crossref PubMed Scopus (110) Google Scholar In previously reported studies, the effects of nutrition were assessed by comparison with a true fasting state.14Hunter K.A. Ballmer P.E. Anderson S.E. et al.Acute stimulation of albumin synthesis rate with oral meal feeding in healthy subjects measured with [ring-2H5]phenylalanine.Clin Sci. 1995; 88: 235-242Crossref PubMed Scopus (65) Google Scholar,15De Feo P. Horber F.F. Haymond M.W. Meal stimulation of albumin synthesis: a significant contributor to whole body protein synthesis in humans.Am J Physiol. 1992; 263: E794-E799PubMed Google Scholar This suggests that the increase in albumin synthesis as found in those studies after a meal containing both protein and carbohydrates could, in part be due to increased insulin secretion. One may speculate that in our studies in fasting PD patients, using G only dialysate, albumin synthesis was already stimulated via insulin, so that supply of intraperitoneal or oral AAs did not induce a significantly further increase of FSR-albumin. It is certainly possible that an even higher protein intake could have resulted in a significant increase of FSR-albumin. Yet the effects on FSR-albumin contrast markedly with the substantially increase in WBPS, demonstrating a differential effect of food on the synthesis rates of albumin and whole-body proteins. WBPS reflects the sum of protein synthesis rates of all tissues and, in particular, of muscle and liver, which together account for the major part of WBPS. Using the forearm perfusion method it has been shown in PD patients that availability of AAs promotes skeletal muscle protein synthesis, whereas insulin has an inhibitory effect on muscle protein breakdown.17Garibotto G. Sofia A. Canepa A. et al.Acute effects of peritoneal dialysis with dialysates containing dextrose or dextrose and amino acids on muscle protein turnover in patients with chronic renal failure.J Am Soc Nephrol. 2001; 12: 557-567PubMed Google Scholar As muscle protein synthesis contributes substantially to WBPS, the stimulating effect of AAs on WBPS may be attributed to a large extent to increased muscle protein synthesis. Protein has also been shown to stimulate hepatic albumin synthesis. In malnutrition and protein-depleted conditions in humans and animals, albumin synthesis was found to be depressed, whereas protein repletion resulted in a prompt recovery.21Kirsch R. Frith L. Black E. Hoffenberg R. Regulation of albumin synthesis and catabolism by alteration of dietary protein.Nature. 1968; 217: 578-579Crossref PubMed Scopus (150) Google Scholar, 22James W.P.T. Hay A.M. Albumin metabolism: effect of the nutritional state and the dietary protein intake.J Clin Invest. 1968; 47: 1958-1972Crossref PubMed Scopus (103) Google Scholar, 23Morgan E.H. Peters T. The biosynthesis of rat serum albumin.J Biol Chem. 1971; 246: 3500-3507Abstract Full Text PDF PubMed Google Scholar In these studies, energy intake was kept constant in the protein-depleted and protein-replenished conditions clearly indicating that proteins and AAs modulate albumin synthesis. In postoperative patients, intravenous administration of AAs and energy each was found to stimulate albumin synthesis.24Skillman J.J. Rosenoer V.M. Smith P.C. Fang M.S. Improved albumin synthesis in postoperative patients by amino acid infusion.New Engl J Med. 1976; 295: 1037-1040Crossref PubMed Scopus (60) Google Scholar In many studies, however, it is not possible to distinguish the effects of insulin and AAs. Moreover, the comparison of studies is complicated by marked differences in patient characteristics, such as the presence or absence of inflammatory conditions,1Kaysen G.A. Biological basis of hypoalbuminemia in ESRD.J Am Soc Nephrol. 1998; 9: 2368-2376PubMed Google Scholar,25Kaysen G.A. Dubin J.A. Müller H.G. et al.Relationships among inflammation nutrition and physiologic mechanism establishing albumin levels in hemodialysis patients.Kidney Int. 2002; 61: 2240-2249Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar and in design including the composition and route of nutrient administration, time frame, and measurement of albumin synthesis rate. In an animal study for example, it was found that the stimulating effect of insulin on albumin synthesis was blunted because of an inhibitory effect on whole-body protein breakdown and AA availability.26Ahlman B. Charlton M. Fu A. et al.Insulin's effect on synthesis rates of liver proteins. A swine model comparing various precursors of protein synthesis.Diabetes. 2001; 50: 947-954Crossref PubMed Scopus (58) Google Scholar There is some evidence that protein depletion make albumin synthesis responsive to protein intake, which suggests that the nutritional state may play an important role in the effects of proteins and calories on albumin synthesis.25Kaysen G.A. Dubin J.A. Müller H.G. et al.Relationships among inflammation nutrition and physiologic mechanism establishing albumin levels in hemodialysis patients.Kidney Int. 2002; 61: 2240-2249Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar,27Gersovitz M. Munro H.N. Udall J. Young V.R. Albumin synthesis in young and elderly subjects using a new stable isotope methodology: response to level of protein intake.Metabolism. 1980; 29: 1075-1086Abstract Full Text PDF PubMed Scopus (124) Google Scholar On the other hand, in healthy subjects with a good nutritional status, albumin synthesis was also found to be stimulated after a meal.14Hunter K.A. Ballmer P.E. Anderson S.E. et al.Acute stimulation of albumin synthesis rate with oral meal feeding in healthy subjects measured with [ring-2H5]phenylalanine.Clin Sci. 1995; 88: 235-242Crossref PubMed Scopus (65) Google Scholar,15De Feo P. Horber F.F. Haymond M.W. Meal stimulation of albumin synthesis: a significant contributor to whole body protein synthesis in humans.Am J Physiol. 1992; 263: E794-E799PubMed Google Scholar In another study in healthy humans, albumin synthesis rates were not found to be responsive to short-term intravenous nutrients, suggesting that the route of administration may also play a role.28Ballmer P.E. McNurlan M.A. Essen P. et al.Albumin synthesis rates measured with [2H5ring] phenylalanine are not responsive to short-term intravenous nutrients in healthy humans.J Nutr. 1995; 125: 512-519PubMed Google Scholar In this study, albumin synthesis was assessed by estimation of the FSR-albumin using stable isotope infusion technique. With this method, enrichment of α-ketoisocaproic acid (KIC) in plasma is measured after infusion with labeled leucine. Other methods include determination of mRNA or the enrichment of liver aminoacyl-tRNA, the direct precursor of albumin synthesis.26Ahlman B. Charlton M. Fu A. et al.Insulin's effect on synthesis rates of liver proteins. A swine model comparing various precursors of protein synthesis.Diabetes. 2001; 50: 947-954Crossref PubMed Scopus (58) Google Scholar For these techniques and for the determination of total liver protein synthesis as well, hepatic tissue samples are required. Plasma KIC enrichment has been proven to be a reliable surrogate measure of leucyl-tRNA in liver.26Ahlman B. Charlton M. Fu A. et al.Insulin's effect on synthesis rates of liver proteins. A swine model comparing various precursors of protein synthesis.Diabetes. 2001; 50: 947-954Crossref PubMed Scopus (58) Google Scholar The contribution of albumin synthesis to total liver protein synthesis is estimated at about 15%.29Barle H. Nyberg B. Essen P. et al.The synthesis rates of total liver protein and plasma albumin determined simultaneously in vivo in humans.Hepatology. 1997; 25: 154-158PubMed Google Scholar Different effects of insulin on the fractional synthesis rates of albumin and another liver protein fibrinogen have been found in several studies.15De Feo P. Horber F.F. Haymond M.W. Meal stimulation of albumin synthesis: a significant contributor to whole body protein synthesis in humans.Am J Physiol. 1992; 263: E794-E799PubMed Google Scholar,18De Feo P. Gaisano M.G. Haymond M.W. Differential effects of insulin deficiency on albumin and fibrinogen synthesis in humans.J Clin Invest. 1991; 88: 833-840Crossref PubMed Google Scholar This is the first study in PD patients to compare the effects of supplementation of intraperitoneal AAs or food on albumin synthesis with those on whole-body protein metabolism. We found that the significant improvements in WBPS were not accompanied by a parallel increase of albumin synthesis. Such a discrepancy is consistent with the finding that the regulation of albumin synthesis is different from that of skeletal muscles and various other hepatic proteins such as fibrinogen. It is worth mentioning that plasma AAs, mainly the essential AAs, increased significantly with both intraperitoneal and oral AA supply. It has been reported that essential AAs, in particular, the branched chain AAs, are responsible for the stimulation of muscle protein anabolism by AAs.30Raj D.S.C. Oladipo A. Lim S. Amino acid and protein kinetics in renal failure. An integrated approach.Semin Nephrol. 2005; 26: 158-166Abstract Full Text Full Text PDF Scopus (22) Google Scholar, 31Raj D.S.C. Adeniyi O. Dominic E.A. et al.Amino acid repletion does not decrease muscle protein catabolism during hemodialysis.Am J Physiol Endocrinol Metab. 2007Crossref Scopus (30) Google Scholar, 32Volpi E. Kobayashi H. Sheffield-Moore M. et al.Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults.Am J Clin Nutr. 2003; 78: 250-258PubMed Google Scholar Our study was conducted in a small, relatively stable and well-nourished population free of liver diseases33Tessari P. Barazzoni R. Kiwanuka E. et al.Impairment of albumin and whole body postprandial protein synthesis in compensated liver cirrhosis.Am J Physiol Endocrinol Metab. 2002; 282: E304-E311Crossref PubMed Scopus (29) Google Scholar or acidosis,34Ballmer P.E. McNurlan M.A. Hulter H.N. et al.Chronic metabolic acidosis decreases albumin synthesis and induces negative nitrogen balance in humans.J Clin Invest. 1995; 95: 39-45Crossref PubMed Google Scholar and without clinical signs of inflammation. In addition, the fact that the fasting patients were not in a true fasting state may have complicated the interpretation of the results. Further work including PD patients in a true fasting state are needed to evaluate the effects of AA plus G containing dialysis solutions in various clinical conditions such as inflammation and malnutrition. Eight patients with end-stage renal failure undergoing Automated Peritoneal Dialysis and 12 patients on Continuous Ambulatory Peritoneal Dialysis were recruited from the Peritoneal Dialysis Unit of the Erasmus Medical Center. Inclusion criteria were for stable patients, undergoing PD for more than 3 months and who had a weekly Kt/V≥1.7. Exclusion criteria included peritonitis, other infectious or inflammatory diseases in the previous 6 weeks, malignant disease, and life expectancy of less than 6 months. The local Medical Ethics Committee approved the study protocol, and written informed consent was obtained from all study patients. The baseline characteristics of the patients included in both studies are summarized in Table 3.Table 3Baseline characteristics of the patients in both studiesaData are mean±s.d.Fasting-state studyFed-state studyNumber of patients812Gender (M/F)6/28/4Age (year)49.3±9.854.8±12.2Time on PD (month)24±2115.9±19.2BMI (kg/m2)26±3.126.4±3.8Kt/V2.0±0.22.41±0.40nPNA (g/kg/day)0.8±0.10.92±0.24BMI, body mass index; F, female; Kt/V, value per week; M, male; nPNA, normalized protein equivalent of nitrogen appearance (PD adequest 2.0, software Baxter); PD, peritoneal dialysis.a Data are mean±s.d. Open table in a new tab BMI, body mass index; F, female; Kt/V, value per week; M, male; nPNA, normalized protein equivalent of nitrogen appearance (PD adequest 2.0, software Baxter); PD, peritoneal dialysis. The plasma FSR-albumin study protocol was designed as an extension of our previous studies on the effects of peritoneal dialysis fluids containing AA and glucose on whole-body protein metabolism.12Tjiong H.L. Van den Berg J.W. Wattimena J.L. et al.Dialysate as food: combined amino acid and glucose dialysate improves protein anabolism in renal failure patients on automated peritoneal dialysis.J Am Soc Nephrol. 2005; 16: 1486-1493Crossref PubMed Scopus (85) Google Scholar,13Tjiong H.L. Rietveld T. Wattimena J.L. et al.Peritoneal dialysis with solutions containing amino acids plus glucose promotes protein synthesis during oral feeding.Clin J Am Soc Nephrol. 2007; 2: 74-80Crossref PubMed Scopus (36) Google Scholar This was an open-label, randomized, cross-over single-center study, comparing FSR-albumin using a dialysis scheme with dialysate containing AA plus G (Nutrineal® 11% plus Physioneal® 1.36–3.86%; Baxter BV, Utrecht, The Netherlands) and a control solution containing only G (Physioneal® 1.36–3.86%). The study was conducted both in the fasting and fed state (Figure 2), and was performed using an automated cycler (HomeChoice®, Baxter BV) to obtain steady-state condition. Each patient was studied on two separate days, with a 1-week interval. The patients were randomly assigned to start with AA plus G or G dialysis. The results of WBPS were all derived from our previously published studies.12Tjiong H.L. Van den Berg J.W. Wattimena J.L. et al.Dialysate as food: combined amino acid and glucose dialysate improves protein anabolism in renal failure patients on automated peritoneal dialysis.J Am Soc Nephrol. 2005; 16: 1486-1493Crossref PubMed Scopus (85) Google Scholar,13Tjiong H.L. Rietveld T. Wattimena J.L. et al.Peritoneal dialysis with solutions containing amino acids plus glucose promotes protein synthesis during oral feeding.Clin J Am Soc Nephrol. 2007; 2: 74-80Crossref PubMed Scopus (36) Google Scholar In the fasting-state study, the dialysis procedure was performed in eight patients on Automated Peritoneal Dialysis during a period of 8.5 h at night. Six exchanges either with AA plus G or G dialysate were carried out automatically using a cycler. In the daytime, there were one or two exchanges with G (Dianeal 1.36–3.86% or Physioneal; Baxter BV) and/or polyglucose-containing dialysate (Extraneal, Baxter BV). Before the study, all Automated Peritoneal Dialysis patients used glucose-based dialysis fluid (Dianeal® or Physioneal®). In the fed-state study, the dialysis procedure was carried out during a period of 9 h at daytime. Six exchanges either with AA plus G or G dialysate were performed automatically using a cycler to obtain steady-state condition during the WBPT study, liquid food was given in equal hourly aliquots. All patients used Extraneal in the night before the study. Before the study, all patients had a dialysis scheme of four exchanges of glucose-based dialysis fluid (Physioneal® 1.36–3.86%) during the day and a dwell of Physioneal® 1.36–3.86% or Extraneal during the night. The composition of the AA 1.1% dialysis solution (g/l) was: histidine 0.714, isoleucine 0.850, leucine 1.020, lysine-HCl 0.955, methionine 0.850, phenylalanine 0.570, threonine 0.646, tryptophane 0.270, valine 1.393, arginine 1.071, alanine 0.951, proline 0.595, glycine 0.510, serine 0.510, and tyrosine 0.300. The electrolyte and buffer concentrations (mmol/l) were: Na 132, Cl 105, Ca 1.25, Mg 0.25, and lactate 40. The electrolyte and buffer composition (mmol/l) of the 1.36, 2.27, or 3.86% G was: Na 132, Cl 95, Ca 1.25, Mg 0.25, bicarbonate 25 mmol/l, and lactate 15 mmol/l. FSR-albumin and WBPS were determined with a stable isotope technique using a primed continuous intravenous infusion of 13C-leucine. Priming doses of L-[1-13C]-leucine (3.8 μmol/kg) and of NaH13CO3 (1.7 μmol/kg) were given to label the leucine and CO2 pools, followed by a continuous infusion of L-[1-13C]-leucine (infusion rate 0.063 μmol/kg/min). In the fasting-state study, the 8.5-h dialysis started at 2030 hours (T0). Continuous leucine infusion was given between 0230 and 0500 hours. Blood samples and expiratory breath samples were collected at 0230 hours (6 h from the start of the dialysis, T360) and 30, 60, 90, 105, 120, 135, and 150 min after priming and starting the tracer infusion at T390, T420, T450, T465, T480, T495, and T510 min. The patients were not allowed to eat during the study. In the fed-state study, baseline blood samples and expiratory breath samples were collected at 0800 hours before starting the oral feeding. At 0830 hours oral feeding consisting of 11 identical portions of a liquid complete nutritional product (Nutridrink® Nutricia, Zoetermeer, The Netherlands) was started and was given at regular hourly intervals to meet a steady-state condition, except for the first three portions that were given at half hourly intervals to induce a fed state-steady state. Other food was not allowed. The dialysis started at 0930 hours (T0). The constant leucine infusion was administrated during the last 3 h of the 9-h dialysis period, started at 1530 hours and was continued for 180 min until the end of the dialysis period at 1830 hours (T540). Blood and expired air samples were simultaneously collected in duplicate at T420,T450,T480,T510, T525, and T540 min, that is at 60, 90, 120, 150, 165, and 180 min after priming and starting the tracer infusion. In both part of the study noncaloric beverages were permitted. The plasma-free 13C leucine enrichment was calculated from the 13C enrichment of KIC as described previously.12Tjiong H.L. Van den Berg J.W. Wattimena J.L. et al.Dialysate as food: combined amino acid and glucose dialysate improves protein anabolism in renal failure patients on automated peritoneal dialysis.J Am Soc Nephrol. 2005; 16: 1486-1493Crossref PubMed Scopus (85) Google Scholar,13Tjiong H.L. Rietveld T. Wattimena J.L. et al.Peritoneal dialysis with solutions containing amino acids plus glucose promotes protein synthesis during oral feeding.Clin J Am Soc Nephrol. 2007; 2: 74-80Crossref PubMed Scopus (36) Google Scholar In brief, the 13C enrichment was determined by gas chromatography-mass spectrometry by measuring the fragments 259 and 260 of the butyldimethylsilylquinoxalinol derivatives of natural KIC and 13C KIC, respectively. In plasma, the measurement of 13C KIC is representative for free 13C leucine. The enrichment of 13C leucine incorporated in albumin was analysed as follows: Heparinized plasma was deproteinized with TCA 20% and centrifugated. Ethanol absolute was then added to dissolve selectively the albumin, leaving other proteins as precipitate. After centrifugation of this solution, the supernatant containing albumin was dried and the residue was taken up in 0.3 mol/l NaOH at 37°C. Albumin was precipitated again from this solution with 2 mol/l HClO4 and the pellet was hydrolysed in 6 mol/l HCL for 24 h at 110°C After drying, the hydrolysate was purified using a cation-exchanger AG 50W-X8, 200–400 mesh, H+ form. The AAs were eluted with 6 mol/l ammonia and converted into the ethoxycarbonyl-ethylester derivative (using ECF ethylchloroformate). The analysis of 13C leucine enrichment in the isolated albumin took place with gas chromatography-combustion interface-isotope ratio mass spectrometry. The AA derivatives were converted into the GC (Thermo Electron, Breda, The Netherlands) using PTV splitless injection. The GC contains a CP-Sil-24 CB lowbleed/MS (Varian, Middleburg, The Netherlands) capillary column (30 m × 0.25 mm, df=0.5 μm) and subsequently column FACTORfour (VF-1701MS, 30 m × 0.25 mm, df=1.00 μm; Varian). The AA derivatives leaving the column were combusted online at 940°C and the CO2 was online introduced into the Delta-XP IRMS (Thermo Finnigan, Bremen, Germany). We measured at masses 44 and 45 for 12CO2 and 13CO2, respectively. In the fasting-state study, blood samples for estimation of insulin were taken in the fasting state before the morning exchange before the study protocol. In the daytime study, blood samples were collected after an overnight fast and drainage of dialysate (before starting with oral nutrition) and at the end of the study days. Blood samples were taken during the AA plus G and G only dialysis at the end of the WBPT study to determine plasma AA levels, both in the fasting- and fed-state study. Insulin was measured by a chemiluminescent immunometric assay (Immulite 2000 Insulin; DPC, Los Angeles, CA, USA). The AAs were measured by ion-exchange chromatography on a Biochrome 20 amino acid analyzer with ninhydrin detection (Biochrome, Cambridge, UK). Other determinations were performed according to routine laboratory procedures. WBPS was calculated from 13C KIC enrichment, 13C leucine infusion rate and the rate of expired 13CO2, as described previously.12Tjiong H.L. Van den Berg J.W. Wattimena J.L. et al.Dialysate as food: combined amino acid and glucose dialysate improves protein anabolism in renal failure patients on automated peritoneal dialysis.J Am Soc Nephrol. 2005; 16: 1486-1493Crossref PubMed Scopus (85) Google Scholar,13Tjiong H.L. Rietveld T. Wattimena J.L. et al.Peritoneal dialysis with solutions containing amino acids plus glucose promotes protein synthesis during oral feeding.Clin J Am Soc Nephrol. 2007; 2: 74-80Crossref PubMed Scopus (36) Google Scholar FSR-albumin is the fraction of the intravascular albumin pool, expressed as percentage, synthesized per day and was calculated as shown in the formula: FSR-albumin (%/day)=(13C leucinealb) × (13C KICave)-1 × 60 × 24 × 100. 13C leucinealb is expressed as mole percent excess (MPE) change per minute of 13C leucine incorporated in albumin. The change in albumin enrichment per min was calculated from the regression line using data between the start and the end of the time period selected for measurements (t=390–540 min). The plasma 13C enrichment of free leucine, represented by (13C KICave) was found by determining the average 13C KIC enrichment from the period of measurement and is expressed as MPE. MPE stands for mole percent excess of the isotopic-labeled molecule that was measured. The other numbers convert the data into percentage fractional synthetic rate per day. Data were analysed using the statistical program SPSS, version 11.0, for Windows (SPSS Inc., Chicago, IL, USA). Data are expressed as mean±s.d., or indicated otherwise. The paired t-test was used to compare differences between the two treatment regimens (AA plus G versus G only dialysis) in the cross-over experiment. The unpaired t-test was used to compare differences regarding FSR-albumin between the fasting- and fed-state study. Differences were considered statistically significant when the two-sided P-value was <0.05. This study was supported by grants from Baxter Benelux. The authors thank the patients for their participation and van Dijk LJ and Kahriman D, PD nurses, van Egmond AM, van der Wiel AM, and van der Steen J, dieticians, and Belder M, nurse, for their cooperation in the studies. We appreciate the assistance from W Cairo-Rawling for amino-acid measurements." @default.
• W2016838197 created "2016-06-24" @default.
• W2016838197 creator A5017581573 @default.
• W2016838197 creator A5027805100 @default.
• W2016838197 creator A5028109035 @default.
• W2016838197 creator A5030100313 @default.
• W2016838197 creator A5031423213 @default.
• W2016838197 creator A5046864690 @default.
• W2016838197 creator A5057618648 @default.
• W2016838197 creator A5080592772 @default.
• W2016838197 creator A5083607539 @default.
• W2016838197 date "2007-08-01" @default.
• W2016838197 modified "2023-10-17" @default.
• W2016838197 title "Albumin and whole-body protein synthesis respond differently to intraperitoneal and oral amino acids" @default.
• W2016838197 cites W1549194029 @default.
• W2016838197 cites W1985020943 @default.
• W2016838197 cites W2002304492 @default.
• W2016838197 cites W2010287624 @default.
• W2016838197 cites W2012700455 @default.
• W2016838197 cites W2013261295 @default.
• W2016838197 cites W2022351209 @default.
• W2016838197 cites W2032932944 @default.
• W2016838197 cites W2036131779 @default.
• W2016838197 cites W2038628870 @default.
• W2016838197 cites W2047409289 @default.
• W2016838197 cites W2050538051 @default.
• W2016838197 cites W2052998622 @default.
• W2016838197 cites W2053541172 @default.
• W2016838197 cites W2063360137 @default.
• W2016838197 cites W2064718511 @default.
• W2016838197 cites W2089057228 @default.
• W2016838197 cites W2096354269 @default.
• W2016838197 cites W2107472020 @default.
• W2016838197 cites W2111253761 @default.
• W2016838197 cites W2126616281 @default.
• W2016838197 cites W2131900734 @default.
• W2016838197 cites W2135419782 @default.
• W2016838197 cites W2137098613 @default.
• W2016838197 cites W2151185613 @default.
• W2016838197 cites W2165652740 @default.
• W2016838197 cites W2256923819 @default.
• W2016838197 cites W2292033102 @default.
• W2016838197 cites W2342131823 @default.
• W2016838197 doi "https://doi.org/10.1038/sj.ki.5002364" @default.
• W2016838197 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17554255" @default.
• W2016838197 hasPublicationYear "2007" @default.
• W2016838197 type Work @default.
• W2016838197 sameAs 2016838197 @default.
• W2016838197 citedByCount "6" @default.
• W2016838197 countsByYear W20168381972019 @default.
• W2016838197 countsByYear W20168381972021 @default.
• W2016838197 crossrefType "journal-article" @default.
• W2016838197 hasAuthorship W2016838197A5017581573 @default.
• W2016838197 hasAuthorship W2016838197A5027805100 @default.
• W2016838197 hasAuthorship W2016838197A5028109035 @default.
• W2016838197 hasAuthorship W2016838197A5030100313 @default.
• W2016838197 hasAuthorship W2016838197A5031423213 @default.
• W2016838197 hasAuthorship W2016838197A5046864690 @default.
• W2016838197 hasAuthorship W2016838197A5057618648 @default.
• W2016838197 hasAuthorship W2016838197A5080592772 @default.
• W2016838197 hasAuthorship W2016838197A5083607539 @default.
• W2016838197 hasBestOaLocation W20168381971 @default.
• W2016838197 hasConcept C126322002 @default.
• W2016838197 hasConcept C134018914 @default.
• W2016838197 hasConcept C165616093 @default.
• W2016838197 hasConcept C185592680 @default.
• W2016838197 hasConcept C2776009029 @default.
• W2016838197 hasConcept C2776125364 @default.
• W2016838197 hasConcept C2776580952 @default.
• W2016838197 hasConcept C2776706248 @default.
• W2016838197 hasConcept C2779056158 @default.
• W2016838197 hasConcept C2779978075 @default.
• W2016838197 hasConcept C515207424 @default.
• W2016838197 hasConcept C55493867 @default.
• W2016838197 hasConcept C71924100 @default.
• W2016838197 hasConceptScore W2016838197C126322002 @default.
• W2016838197 hasConceptScore W2016838197C134018914 @default.
• W2016838197 hasConceptScore W2016838197C165616093 @default.
• W2016838197 hasConceptScore W2016838197C185592680 @default.
• W2016838197 hasConceptScore W2016838197C2776009029 @default.
• W2016838197 hasConceptScore W2016838197C2776125364 @default.
• W2016838197 hasConceptScore W2016838197C2776580952 @default.
• W2016838197 hasConceptScore W2016838197C2776706248 @default.
• W2016838197 hasConceptScore W2016838197C2779056158 @default.
• W2016838197 hasConceptScore W2016838197C2779978075 @default.
• W2016838197 hasConceptScore W2016838197C515207424 @default.
• W2016838197 hasConceptScore W2016838197C55493867 @default.
• W2016838197 hasConceptScore W2016838197C71924100 @default.
• W2016838197 hasIssue "3" @default.
• W2016838197 hasLocation W20168381971 @default.
• W2016838197 hasLocation W20168381972 @default.
• W2016838197 hasOpenAccess W2016838197 @default.
• W2016838197 hasPrimaryLocation W20168381971 @default.
• W2016838197 hasRelatedWork W2002304492 @default.
• W2016838197 hasRelatedWork W2013998904 @default.
• W2016838197 hasRelatedWork W2042899237 @default.
• W2016838197 hasRelatedWork W2050213379 @default.
• W2016838197 hasRelatedWork W2066809553 @default.

• next