Background/Aims: Hemoadsorption may improve outcomes for sepsis by removing circulating cytokines. We tested a new sorbent used for hemoadsorption. Methods: CTR sorbent beads were filled into columns of three sizes: CTR0.5 (0.5 ml), CTR1 (1.0 ml) and CTR2 (2.0 ml) and tested using IL-6 capture in vitro. Next, rats were subjected to cecal ligation and puncture and randomly assigned to hemoadsorption with CTR0.5, CTR1, CTR2 or sham treatment. Plasma biomarkers were measured. Results: In vitro, IL-6 removal was accelerated with increasing bead mass. In vivo, TNF, IL-6, IL-10, high mobility group box1, and cystatin C were significantly lower 24 h after CTR2 treatment. Seven-day survival rate was 50, 64, 63, and 73% for the sham, CTR0.5, CTR1, CTR2, respectively. Conclusion: CTR appeared to have a favorable effect on kidney function despite no immediate effects on cytokine removal. However, CTR2 beads did result in a late decrease of cytokines.

Keywords:
Sepsis, Cytokines, Interleukin-6, Hemoadsorption, Necrosis factor, Sorbents, Acute kidney injury
1.
Bone RC: The pathogenesis of sepsis. Ann Intern Med 1991;115:457-469.
2.
Jacobi J: Pathophysiology of sepsis. Am J Health Syst Pharm 2002;59(suppl 1):S3-S8.
3.
Peng ZY, Wang HZ, Srisawat N, Wen X, Rimmelé T, Bishop J, Singbartl K, Murugan R, Kellum JA: Bactericidal antibiotics temporarily increase inflammation and worsen acute kidney injury in experimental sepsis. Crit Care Med 2012;40:538-543.
4.
Zhou F, Peng ZY, Bishop JV, Cove ME, Singbartl K, Kellum JA: Effects of fluid resuscitation with 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis. Crit Care Med 2014;42:e270-e278.
5.
Rimmelé T, Kellum JA: Clinical review: blood purification for sepsis. Crit Care 2011;15:205.
6.
Peng Z, Singbartl K, Simon P, Rimmelé T, Bishop J, Clermont G, Kellum JA: Blood purification in sepsis: a new paradigm. Contrib Nephrol 2010;165:322-328.
7.
Kellum JA, Kong L, Fink MP, Weissfeld LA, Yealy DM, Pinsky MR, Fine J, Krichevsky A, Delude RL, Angus DC: Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the genetic and inflammatory markers of sepsis (GenIMS) study. Arch Intern Med 2007;167:1655-1663.
8.
Kellum JA, Song M, Venkataraman R: Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-kappa B DNA binding, and improves short-term survival in lethal endotoxemia. Crit Care Med 2004;32:801-805.
9.
Peng ZY, Bishop JV, Wen XY, Elder MM, Zhou F, Chuasuwan A, Carter MJ, Devlin JE, Kaynar AM, Singbartl K, Pike F, Parker RS, Clermont G, Federspiel WJ, Kellum JA: Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model. Crit Care 2014;18:R141.
10.
Peng ZY, Carter MJ, Kellum JA: Effects of hemoadsorption on cytokine removal and short-term survival in septic rats. Crit Care Med 2008;36:1573-1577.
11.
Peng ZY, Wang HZ, Carter MJ, Dileo MV, Bishop JV, Zhou FH, Wen XY, Rimmelé T, Singbartl K, Federspiel WJ, Clermont G, Kellum JA: Acute removal of common sepsis mediators does not explain the effects of extracorporeal blood purification in experimental sepsis. Kidney Int 2012;81:363-369.
12.
Namas RA, Namas R, Lagoa C, Barclay D, Mi Q, Zamora R, Peng Z, Wen X, Fedorchak MV, Valenti IE, Federspiel WJ, Kellum JA, Vodovotz Y: Hemoadsorption reprograms inflammation in experimental gram-negative septic peritonitis: insights from in vivo and in silico studies. Mol Med 2012;18:1366-1374.
13.
Perego AF: Adsorption techniques: dialysis sorbents and membranes. Blood Purif 2013;35(suppl 2):48-51.
14.
Taniguchi T, Hirai F, Takemoto Y, Tsuda K, Yamamoto K, Inaba H, Sakurai H, Furuyoshi S, Tani N: A novel adsorbent of circulating bacterial toxins and cytokines: the effect of direct hemoperfusion with CTR column for the treatment of experimental endotoxemia. Crit Care Med 2006;34:800-806.
15.
Peng ZY, Zhang J, Rimmelé T, Zhou F, Chuasuwan A, Kaynar AM, Kellum JA: Development of venovenous extracorporeal blood purification circuits in rodents for sepsis. J Surg Res 2013;185:790-796.
16.
Zhou F, Peng Z, Murugan R, Kellum JA: Blood purification and mortality in sepsis: a meta-analysis randomized trials. Crit Care Med 2013;41:2209-2220.
17.
Murugan R, Wen X, Shah N, Lee M, Kong L, Pike F, Keener C, Unruh M, Finkel K, Vijayan A, Palevsky PM, Paganini E, Carter M, Elder M, Kellum JA: Plasma inflammatory and apoptosis markers are associated with dialysis dependence and death among critically ill patients receiving renal replacement therapy. Nephrol Dial Transplant 2014;29:1854-1864.
18.
Joannes-Boyau O, Honoré PM, Perez P, Bagshaw SM, Grand H, Canivet JL, Dewitte A, Flamens C, Pujol W, Grandoulier AS, Fleureau C, Jacobs R, Broux C, Floch H, Branchard O, Franck S, Rozé H, Collin V, Boer W, Calderon J, Gauche B, Spapen HD, Janvier G, Ouattara A: High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial. Intensive Care Med 2013;39:1535-1546.
19.
Clark E, Molnar AO, Joannes-Boyau O, Honoré PM, Sikora L, Bagshaw SM: High-volume hemofiltration for septic acute kidney injury: a systematic review and meta-analysis. Crit Care 2014;18:R7.
20.
Kellum JA, Dishart MK: Effect of hemofiltration filter adsorption on circulating IL-6 levels in septic rats. Crit Care 2002;6:429-433.
21.
Honore PM, Joannes-Boyau O: High volume hemofiltration (HVHF) in sepsis: a comprehensive review of rationale, clinical applicability, potential indications and recommendations for future research. Int J Artif Organs 2004;27:1077-1082.
22.
Honoré PM, Matson JR: Extracorporeal removal for sepsis: acting at the tissue level - the beginning of a new era for this treatment modality in septic shock. Crit Care Med 2004;32:896-897.
23.
Rimmelé T, Kaynar AM, McLaughlin JN, Bishop JV, Fedorchak MV, Chuasuwan A, Peng Z, Singbartl K, Frederick DR, Zhu L, Carter M, Federspiel WJ, Zeevi A, Kellum JA: Leukocyte capture and modulation of cell-mediated immunity during human sepsis: an ex vivo study. Crit Care 2013;17:R59.
© 2015 S. Karger AG, Basel
2015
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