Background: We estimated the flow of endotoxins (ET) from dialysates into the blood of patients on hemodialysis (HD) using limulus amebocyte lysate (LAL) assays and endotoxin activity (EA) determined by neutrophil respiratory burst activity. Methods: A cross-sectional study compared groups given ultrapure bicarbonate (n = 15; group A), acetate-free bicarbonate dialysates (n = 20; group B) and conventional bicarbonate dialysate (n = 23; group C). A prospective study of group C examined the effect of changing the purity of the dialysate. Biomarkers of inflammation and oxidative stress were measured and ET in blood was assessed by LAL assays and EA. Results: Serum ET levels did not differ among the groups, whereas EA and the biomarkers were significantly increased in group C compared with those in groups A and B. HD using conventional dialysate was independently associated with an increase in EA. Purifying the dialysate significantly decreased EA in group C. Conclusion: Measuring EA is useful to assess the influence of dialysate contamination in HD patients.

Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, Berglund L, Jogestrand T: Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int 1999;55:1899–1911.
Kaysen GA, Levin NW, Mitch WE, Chapman AL, Kubala L, Eiserich JP: Evidence that C-reactive protein or IL-6 are not surrogates for all inflammatory cardiovascular risk factors in hemodialysis patients. Blood Purif 2006;24:508–516.
Dukkipati R, Kopple J: Causes and prevention of protein-energy wasting in chronic kidney failure. Semin Nephrol 2009;29:39–49.
Kato S, Chmielewski M, Honda H, Pecoits-Filho R, Matsuo S, Yuzawa Y, Tranaeus A, Stenvinkel P, Lindholm B: Aspects of immune dysfunction in end-stage renal disease. Clin J Am Soc Nephrol 2008;3:1526–1533.
Schindler R, Beck W, Deppisch R, Aussieker M, Wilde A, Göhl H, Frei U: Short bacterial DNA fragments: detection in dialysate and induction of cytokines. J Am Soc Nephrol 2004;15:3207–3214.
Glorieux G, Schepers E, Schindler R, Lemke HD, Verbeke F, Dhondt A, Lameire N, Vanholder R: A novel bio-assay increases the detection yield of microbiological impurity of dialysis fluid, in comparison to the LAL-test. Nephrol Dial Transplant 2009;24:548–554.
Trent M, Stead C, Tran A, Hankins J: Diversity of endotoxin and its impact on pathogenesis. J Endotoxin Res 2006;12:205–223.
Hoenich NA, Ronco C, Levin R: The importance of water quality and haemodialysis fluid composition. Blood Purif 2006;24:11–18.
Bommer J, Jaber BL: Ultrapure dialysate: facts and myths. Semin Dial 2006;19:115–119.
Honda H, Suzuki H, Hosaka N, Hirai Y, Sanada D, Nakamura M, Nagai H, Ashikaga E, Matsumoto K, Mukai M, Watanabe M, Akizawa T: Ultrapure dialysate influences serum myeloperoxidase levels and lipid metabolism. Blood Purif 2009;28:29–39.
Ward R, McLeish K: Oxidant stress in hemodialysis patients: what are the determining factors? Artif Organs 2003;27:230–236.
Lonnemann G: The quality of dialysate: an integrated approach. Kidney Int Suppl 2000;76:S112–S119.
Hoenich N, Thijssen S, Kitzler T, Levin R, Ronco C: Impact of water quality and dialysis fluid composition on dialysis practice. Blood Purif 2008;26:6–11.
Vanholder R, Van Haecke E, Veys N, Ringoir S: Endotoxin transfer through dialysis membranes: small- versus large-pore membranes. Nephrol Dial Transplant 1992;7:333–339.
Tellingen A, Grooteman M, Pronk R, van Loon J, Vervloet M, ter Wee P, Nubé M: Lipopolysaccharide concentrations during superflux dialysis using unfiltered bicarbonate dialysate. ASAIO J 2002;48:383–388.
Romaschin A, Harris D, Ribeiro M, Paice J, Foster D, Walker P, Marshall J: A rapid assay of endotoxin in whole blood using autologous neutrophil dependent chemiluminescence. J Immunol Methods 1998;212:169–185.
Kawanishi H, Akiba T, Masakane I, Tomo T, Mineshima M, Kawasaki T, Hirakata H, Akizawa T: Standard on microbiological management of fluids for hemodialysis and related therapies by the Japanese Society for Dialysis Therapy 2008. Ther Apher Dial 2009;13:161–166.
Honda H, Ueda M, Kojima S, Mashiba S, Suzuki H, Hosaka N, Hirai Y, Nakamura M, Nagai H, Kato N, Mukai M, Watanabe M, Takahashi K, Shishido K, Akizawa T: Oxidized high-density lipoprotein is associated with protein-energy wasting in maintenance hemodialysis patients. Clin J Am Soc Nephrol 2010;5:1021–1028.
Aoki H, Kodama M, Tani T, Hanasawa K: Treatment of sepsis by extracorporeal elimination of endotoxin using polymyxin B-immobilized fiber. Am J Surg 1994;167:412–417.
Tsuchiya M, Oishi H, Takaoka A, Fusamoto M, Matsuura S: Discrimination between endotoxin and (1–3)-beta-D-glucan using turbidimetric kinetic assay with Limulus amebocyte lysate. Chem Pharm Bull (Tokyo) 1990;38:2523–2526.
Marshall J, Foster D, Vincent J, Cook D, Cohen J, Dellinger R, Opal S, Abraham E, Brett S, Smith T, Mehta S, Derzko A, Romaschin A: Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study. J Infect Dis 2004;190:527–534.
Alberti A, Bolognini L, Macciantelli D, Carratelli M: The radical cation of N,N-diethyl-para-phenylenediamine: a possible indicator of oxidative stress in biological samples. Res Chem Intermed 2000;26:253–256.
Motoi Y, Oohashi T, Hirose H, Hiramatsu M, Miyazaki S, Nagasawa S, Takahashi J: Turbidimetric-kinetic assay of endotoxin in rumen fluid or serum of cattle fed rations containing various levels of rolled barley. J Vet Med Sci 1993;55:19–25.
Cliff R, Kwasiborski V, Rudolph A: A comparative study of the accurate measurement of endotoxin in liposome-encapsulated hemoglobin. Artif Cells Blood Substit Immobil Biotechnol 1995;23:331–336.
Marshall J, Walker P, Foster D, Harris D, Ribeiro M, Paice J, Romaschin,A, Derzko A: Measurement of endotoxin activity in critically ill patients using whole blood neutrophil dependent chemiluminescence. Crit Care 2002;6:342–348.
Roslansky P, Novitsky T: Sensitivity of Limulus amebocyte lysate (LAL) to LAL-reactive glucans. J Clin Microbiol 1991;29:2477–2483.
Takayama K, Qureshi N, Raetz C, Ribi E, Peterson J, Cantrell J, Pearson F, Wiggins J, Johnson A: Influence of fine structure of lipid A on Limulus amebocyte lysate clotting and toxic activities. Infect Immun 1984;45:350–355.
Proctor R, Textor J: Activation and inhibition of Limulus amebocyte lysate coagulation by chemically defined substructures of lipid A. Infect Immun 1985;49:286–290.
Todeschini M, Macconi D, Fernández N, Ghilardi M, Anabaya A, Binda E, Morigi M, Cattaneo D, Perticucci E, Remuzzi G, Noris M: Effect of acetate-free biofiltration and bicarbonate hemodialysis on neutrophil activation. Am J Kidney Dis 2002;40:783–793.
Goto T, Edén S, Nordenstam G, Sundh V, Svanborg-Edén C, Mattsby-Baltzer I: Endotoxin levels in sera of elderly individuals. Clin Diagn Lab Immunol 1994;1:684–688.
Wiedermann C, Kiechl S, Dunzendorfer S, Schratzberger P, Egger G, Oberhollenzer F, Willeit J: Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck Study. J Am Coll Cardiol 1999;34:1975–1981.
Pirlich M, Norman K, Lochs H, Bauditz J: Role of intestinal function in cachexia. Curr Opin Clin Nutr Metab Care 2006;9:603–606.
Kallio K, Buhlin K, Jauhiainen M, Keva R, Tuomainen A, Klinge B, Gustafsson A, Pussinen P: Lipopolysaccharide associates with pro-atherogenic lipoproteins in periodontitis patients. Innate Immun 2008;14:247–253.
Lee M, Ide M, Coward P, Wilson R: Effect of ultrasonic debridement using a chlorhexidine irrigant on circulating levels of lipopolysaccharides and interleukin-6. J Clin Periodontol 2008;35:415–419.
Stenvinkel P, Holmberg I, Heimbürger O, Diczfalusy U: A study of plasmalogen as an index of oxidative stress in patients with chronic renal failure. Evidence of increased oxidative stress in malnourished patients. Nephrol Dial Transplant 1998;13:2594–2600.
Honda H, Ueda M, Kojima S, Mashiba S, Hirai Y, Hosaka N, Suzuki H, Mukai M, Watanabe M, Takahashi K, Shishido K, Akizawa T: Assessment of myeloperoxidase and oxidative alpha1-antitrypsin in patients on hemodialysis. Clin J Am Soc Nephrol 2009;4:142–151.
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