Short-Term Effects of a New Bicarbonate/Lactate-Buffered and Conventional Peritoneal Dialysis Fluid on Peritoneal and Systemic Inflammation in CAPD Patients: A Randomized Controlled Study
Restricted accessResearch articleFirst published online January, 2008
Short-Term Effects of a New Bicarbonate/Lactate-Buffered and Conventional Peritoneal Dialysis Fluid on Peritoneal and Systemic Inflammation in CAPD Patients: A Randomized Controlled Study
This study was designed to compare the local peritoneal and systemic inflammatory effects of a conventional lactate-based (Lac) peritoneal dialysis (PD) solution and a new biocompatible bicarbonate/lactate-based (Bic/ Lac) solution having low concentration of glucose degradation products.
Methods
26 stable, prevalent PD patients were enrolled in this prospective study. They sequentially underwent 3 months of therapy with the Lac solution and 3 months with the Bic/Lac solution in a randomized order. Flow cytometry was used to measure the expression of inflammatory molecules on peritoneal cells in overnight effluent collected at the end of each study period.
Results
21 patients successfully completed the study. Mean fluorescence intensity of human leukocyte antigen (HLA)-DR and CD14 expression by macrophages were not different between Lac and Bic/Lac. The peritoneal appearance rate of cancer antigen 125 (kU/minute) was 68 ± 37 with Lac and 133 ± 66 with Bic/Lac (p < 0.001), and of interleukin (IL)-6 (ng/minute), 0.28 ± 0.2 with Lac and 0.18 ± 0.16 with Bic/Lac (p = 0.014). HLA-DR macrophage expression and IL-6 peritoneal appearance rates did not correlate. Serum concentrations with Lac and Bic/Lac were, for IL-6, 3.49 ± 2.28 and 3.72 ± 2.46 ng/L (p = 0.17), and for high-sensitivity C-reactive protein, 2.31 ± 2.98 and 2.71 ± 3.31 mg/L (p = 0.32) respectively. The concentration of effluent macrophages (x106/L) with Lac was 1.6 ± 1.6 and with Bic/Lac 2.6 ± 3.3 (p = 0.07).
Conclusions
We conclude that, although there was a significant reduction in peritoneal IL-6 in patients using Bic/ Lac solution, systemic levels of inflammatory markers did not differ between the two solutions and no changes were present in macrophage surface activation markers, suggesting perhaps a less important role of peritoneal macrophages in the intraperitoneal chronic inflammatory process. The number of effluent macrophages tended to be higher in patients using the Bic/Lac solution, possibly contributing to improved intraperitoneal defense.
WangA.Y., WooJ., LamC.W., WangM., SeaM.M., LuiS.F.Is a single time point C-reactive protein predictive of outcome in peritoneal dialysis patients?J Am Soc Nephrol2003; 14: 1871–9.
2.
Pecoits-FilhoR., BaranyP., LindholmB., HeimburgerO., StenvinkelP.Interleukin-6 is an independent predictor of mortality in patients starting dialysis treatment.Nephrol Dial Transplant2002; 17: 1684–8.
3.
Pecoits-FilhoR., StenvinkelP., WangA.Y., HeimburgerO., LindholmB.Chronic inflammation in peritoneal dialysis: the search for the holy grail?Perit Dial Int2004; 24: 327–39.
4.
LibettaC., De NicolaL., RampinoT., De SimoneW., MemoliB.Inflammatory effects of peritoneal dialysis: evidence of systemic monocyte activation.Kidney Int1996; 49: 506–11.
5.
DaviesS.J., SuassunaJ., OggC.S., CameronJ.S.Activation of immunocompetent cells in the peritoneum of patients treated with CAPD.Kidney Int1989; 36: 661–8.
6.
BraunerA., HylanderB., JacobsonS.H., MoshfeghA., LundahlJ.Increased expression of CD25 and HLA-DR on lymphocytes recruited into the peritoneal cavity in non-infected CAPD patients.Inflammation2001; 25: 399–404.
7.
BraunerA., LuY., HalldenG., HylanderB., LundahlJ.Difference in the blood monocyte phenotype between uremic patients and healthy controls: its relation to monocyte differentiation into macrophages in the peritoneal cavity.Inflammation1998; 22: 55–66.
ZareieM., HekkingL.H., WeltenA.G., DriesprongB.A., Schadee-EestermansI.L., FaictD.Contribution of lactate buffer, glucose and glucose degradation products to peritoneal injury in vivo.Nephrol Dial Transplant2003; 18: 2629–37.
10.
van BronswijkH., VerbrughH.A., BosH.J., HeeziusE.C., OeP.L., van der MeulenJ.Cytotoxic effects of commercial continuous ambulatory peritoneal dialysis (CAPD) fluids and of bacterial exoproducts on human mesothelial cells in vitro.Perit Dial Int1989; 9: 197–202.
11.
CendorogloM., SundaramS., GrovesC., UcciA.A., JaberB.L., PereiraB.J.Necrosis and apoptosis of polymorphonuclear cells exposed to peritoneal dialysis fluids in vitro.Kidney Int1997; 52: 1626–34.
12.
WitowskiJ., BenderT.O., Wisniewska-ElnurJ., KsiazekK., Passlick-DeetjenJ., BreborowiczA.Mesothelial toxicity of peritoneal dialysis fluids is related primarily to glucose degradation products, not to glucose per se.Perit Dial Int2003; 23: 381–90.
13.
OkabeE., TomoT., TezonoK., KikuchiH., KadotaJ., NasuM.Synergistic cytotoxicity of acidity and glucose degradation products in peritoneal dialysis fluid.J Artif Organs2004; 7: 155–60.
14.
WeltenA.G., SchalkwijkC.G., ter WeeP.M., MeijerS., van den BornJ., BeelenR.J.Single exposure of mesothelial cells to glucose degradation products (GDPs) yields early advanced glycation end-products (AGEs) and a proinflammatory response.Perit Dial Int2003; 23: 213–21.
15.
SchmidtA.M., YanS.D., WautierJ.L., SternD.Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis.Circ Res1999; 84: 489–97.
16.
ChavakisT., BierhausA., NawrothP.P.RAGE (receptor for advanced glycation end products): a central player in the inflammatory response.Microbes Infect2004; 6: 1219–25.
17.
BoulangerE., WautierM.P., WautierJ.L., BovalB., PanisY., WernertN.AGEs bind to mesothelial cells via RAGE and stimulate VCAM-1 expression.Kidney Int2002; 61: 148–56.
18.
BastaG., LazzeriniG., MassaroM., SimonciniT., TanganelliP., FuC.Advanced glycation end products activate endothelium through signal-transduction receptor RAGE: a mechanism for amplification of inflammatory responses.Circulation2002; 105: 816–22.
19.
SchwengerV., MorathC., SalavaA., AmannK., SereginY., DeppischR.Damage to the peritoneal membrane by glucose degradation products is mediated by the receptor for advanced glycation end-products.J Am Soc Nephrol2006; 17: 199–207.
20.
CookerL.A., LuneburgP., HolmesC.J., JonesS., TopleyN; Bicarbonate/Lactate Study Group. Interleukin-6 levels decrease in effluent from patients dialyzed with bicarbonate/lactate-based peritoneal dialysis solutions.Perit Dial Int2001; 21(Suppl 3): S102–7.
21.
WilliamsJ.D., TopleyN., CraigK.J., MackenzieR.K., PischetsriederM., LageC.The Euro-Balance Trial: the effect of a new biocompatible peritoneal dialysis fluid (balance) on the peritoneal membrane.Kidney Int2004; 66: 408–18.
22.
TranaeusA.A long-term study of a bicarbonate/lactate-based peritoneal dialysis solution—clinical benefits. The Bicarbonate/Lactate Study Group.Perit Dial Int2000; 20: 516–23.
23.
SchalkwijkC.G., ter WeeP.M., TeerlinkT.Reduced 1,2-dicarbonyl compounds in bicarbonate/lactate-buffered peritoneal dialysis (PD) fluids and PD fluids based on glucose polymers or amino acids.Perit Dial Int2000; 20: 784–801.
24.
SennS.Cross-over Trials in Clinical Research.Chichester, UK: John Wiley & Sons Ltd; 1993.
25.
Pecoits-FilhoR., AraujoM.R.T., LindholmB., StenvinkelP., AbensurH., RomaoJ.E.Plasma and dialysate IL-6 and VEGF concentrations are associated with high peritoneal solute transport rate.Nephrol Dial Transplant2002; 17: 1480–6.
26.
SundaramS., CendorogloM., CookerL.A., JaberB.L., FaictD., HolmesC.J.Effect of two-chambered bicarbonate lactate-buffered peritoneal dialysis fluids on peripheral blood mononuclear cell and polymorphonuclear cell function in vitro.Am J Kidney Dis1997; 30: 680–9.
27.
MacKenzieR.K., HolmesC.J., MoseleyA., JenkinsJ.P., WilliamsJ.D., ColesG.A.Bicarbonate/lactate- and bicarbonate-buffered peritoneal dialysis fluids improve ex vivo peritoneal macrophage TNFalpha secretion.J Am Soc Nephrol1998; 9: 1499–506.
28.
MackenzieR.K., JonesS., MoseleyA., HolmesC.J., ArgyleR., WilliamsJ.D.In vivo exposure to bicarbonate/lactate- and bicarbonate-buffered peritoneal dialysis fluids improves ex vivo peritoneal macrophage function.Am J Kidney Dis2000; 35: 112–21.
29.
JonesS., HolmesC.J., MackenzieR.K., SteadR., ColesG.A., WilliamsJ.D.Continuous dialysis with bicarbonate/ lactate-buffered peritoneal dialysis fluids results in a long-term improvement in ex vivo peritoneal macrophage function.J Am Soc Nephrol2002; 13(Suppl 1): S97–103.
30.
MortierS., De VrieseA.S., McLoughlinR.M., TopleyN., SchaubT.P., Passlick-DeetjenJ.Effects of conventional and new peritoneal dialysis fluids on leukocyte recruitment in the rat peritoneal membrane.J Am Soc Nephrol2003; 14: 1296–306.
31.
SuassunaJ.H., Das NevesF.C., HartleyR.B., OggC.S., CameronJ.S.Immunohistochemical studies of the peritoneal membrane and infiltrating cells in normal subjects and in patients on CAPD.Kidney Int1994; 46: 443–54.
32.
JonassonP., AlbrektssonA., LjungmanS., WieslanderA., BraideM.Peritoneal leukocyte survival and respiratory burst responses in patients treated with a low glucose degradation and high pH peritoneal dialysis fluid.Int J Artif Organs2003; 26: 121–8.
33.
CatalanM.P., ReyeroA., EgidoJ., OrtizA.Acceleration of neutrophil apoptosis by glucose-containing peritoneal dialysis solutions: role of caspases.J Am Soc Nephrol2001; 12: 2442–9.
34.
WitowskiJ., KorybalskaK., WisniewskaJ., BreborowiczA., GahlG.M., FreiU.Effect of glucose degradation products on human peritoneal mesothelial cell function.J Am Soc Nephrol2000; 11: 729–39.
35.
WitowskiJ., WisniewskaJ., KorybalskaK., BenderT.O., BreborowiczA., GahlG.M.Prolonged exposure to glucose degradation products impairs viability and function of human peritoneal mesothelial cells.J Am Soc Nephrol2001; 12: 2434–41.
36.
KredietR.T.Dialysate cancer antigen 125 concentration as marker of peritoneal membrane status in patients treated with chronic peritoneal dialysis.Perit Dial Int2001; 21: 560–7.
37.
VisserC.E., Brouwer-SteenbergenJ.J., BetjesM.G., KoomenG.C., BeelenR.H., KredietR.T.Cancer antigen 125: a bulk marker for the mesothelial mass in stable peritoneal dialysis patients.Nephrol Dial Transplant1995; 10: 64–9.
38.
Ho-dac-PannekeetM.M., HiralallJ.K., StruijkD.G., KredietR.T.Longitudinal follow-up of CA125 in peritoneal effluent.Kidney Int1997; 51: 888–93.
39.
JonesS., HolmesC.J., KredietR.T., MackenzieR., FaictD., TranaeusA.; Bicarbonate/Lactate Study Group. Bicarbonate/lactate-based peritoneal dialysis solution increases cancer antigen 125 and decreases hyaluronic acid levels.Kidney Int2001; 59: 1529–38.
40.
RippeB., SimonsenO., HeimbürgerO., ChristenssonA., HaraldssonB., StelinG.Long-term clinical effects of a peritoneal dialysis fluid with less glucose degradation products.Kidney Int2001; 59: 348–57.
41.
Pecoits-FilhoR., LindholmB., StenvinkelP.End-stage renal disease: a state of chronic inflammation and hyperleptinemia.Eur J Clin Invest2003; 33: 527–8.
42.
Descamps-LatschaB., HerbelinA., NguyenA.T., Roux-LombardP., ZingraffJ., MoynotA.Balance between IL-1 beta, TNF-alpha, and their specific inhibitors in chronic renal failure and maintenance dialysis. Relationships with activation markers of T cells, B cells, and monocytes.J Immunol1995; 154: 882–92.
43.
SulimanM.E., HeimbürgerO., BárányP., AnderstamB., Pecoits-FilhoR., Rodríguez AyalaE.Plasma pentosidine is associated with inflammation and malnutrition in end-stage renal disease patients starting on dialysis therapy.J Am Soc Nephrol2003; 14: 1614–22.
44.
SchwedlerS., SchinzelR., VaithP., WannerC.Inflammation and advanced glycation end products in uremia: simple coexistence, potentiation or causal relationship?Kidney Int Suppl2001; 78: S32–6.
45.
LyonC.J., LawR.E., HsuehW.A.Minireview: adiposity, inflammation, and atherogenesis.Endocrinology2003; 144: 2195–200.
46.
HerzigK.A., PurdieD.M., ChangW., BrownA.M., HawleyC.M., CampbellS.B.Is C-reactive protein a useful predictor of outcome in peritoneal dialysis patients?J Am Soc Nephrol2001; 12: 814–21.
47.
ChungS.H., HeimbürgerO., StenvinkelP., QureshiA.R., LindholmB.Association between residual renal function, inflammation and patient survival in new peritoneal dialysis patients.Nephrol Dial Transplant2003; 18: 590–7.
