Polymyxin-B hemoperfusion inactivates circulating proapoptotic factors
Vincenzo Cantaluppi, Barbara Assenzio, Daniela Pasero, Giuseppe Mauriello Romanazzi, Alfonso Pacitti, Giacomo Lanfranco, Valeria Puntorieri, Erica L Martin, Luciana Mascia, Gianpaola Monti, Giampaolo Casella, Giuseppe Paolo Segoloni, Giovanni Camussi, V Marco Ranieri, Vincenzo Cantaluppi, Barbara Assenzio, Daniela Pasero, Giuseppe Mauriello Romanazzi, Alfonso Pacitti, Giacomo Lanfranco, Valeria Puntorieri, Erica L Martin, Luciana Mascia, Gianpaola Monti, Giampaolo Casella, Giuseppe Paolo Segoloni, Giovanni Camussi, V Marco Ranieri
Abstract
Objective: To test the hypothesis that extracorporeal therapy with polymyxin B (PMX-B) may prevent Gram-negative sepsis-induced acute renal failure (ARF) by reducing the activity of proapoptotic circulating factors.
Setting: Medical-Surgical Intensive Care Units.
Patients and interventions: Sixteen patients with Gram-negative sepsis were randomized to receive standard care (Surviving Sepsis Campaign guidelines) or standard care plus extracorporeal therapy with PMX-B.
Measurements and results: Cell viability, apoptosis, polarity, morphogenesis, and epithelial integrity were evaluated in cultured tubular cells and glomerular podocytes incubated with plasma from patients of both groups. Renal function was evaluated as SOFA and RIFLE scores, proteinuria, and tubular enzymes. A significant decrease of plasma-induced proapoptotic activity was observed after PMX-B treatment on cultured renal cells. SOFA and RIFLE scores, proteinuria, and urine tubular enzymes were all significantly reduced after PMX-B treatment. Loss of plasma-induced polarity and permeability of cell cultures was abrogated with the plasma of patients treated with PMX-B. These results were associated to a preserved expression of molecules crucial for tubular and glomerular functional integrity.
Conclusions: Extracorporeal therapy with PMX-B reduces the proapoptotic activity of the plasma of septic patients on cultured renal cells. These data confirm the role of apoptosis in the development of sepsis-related ARF.
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References
- Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med. 2004;351:159–169. doi: 10.1056/NEJMra032401.
- Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–1310. doi: 10.1097/00003246-200107000-00002.
- Cunningham PN, Wang Y, Guo R, He G, Quigg RJ. Role of Toll-like receptor 4 in endotoxin-induced acute renal failure. J Immunol. 2004;172:2629–2635.
- Jo SK, Cha DR, Cho WY, Kim HK, Chang KH, Yun SY, Won NH. Inflammatory cytokines and lipopolysaccharide induce Fas-mediated apoptosis in renal tubular cells. Nephron. 2002;91:406–415. doi: 10.1159/000064280.
- Guo R, Wang Y, Minto AW, Quigg RJ, Cunningham PN. Acute renal failure in endotoxemia is dependent on caspase activation. J Am Soc Nephrol. 2004;15:3093–3102. doi: 10.1097/01.ASN.0000145530.73247.F5.
- Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, Buchman TG, Karl IE. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med. 1999;27:1230–1251. doi: 10.1097/00003246-199907000-00002.
- Linton AL, Walker JF, Lindsay RM, Sibbald WJ. Acute renal failure and tubular damage due to sepsis in an animal model. Proc Eur Dial Transplant Assoc Eur Ren Assoc. 1985;21:837–842.
- Shoji H. Extracorporeal endotoxin removal for the treatment of sepsis: endotoxin adsorption cartridge (Toraymyxin) Ther Apher Dial. 2003;7:108–114. doi: 10.1046/j.1526-0968.2003.00005.x.
- Vincent JL, Laterre PF, Cohen J, Burchardi H, Bruining H, Lerma FA, Wittebole X, De Backer D, Brett S, Marzo D, Nakamura H, John S. A pilot-controlled study of a polymyxin B-immobilized hemoperfusion cartridge in patients with severe sepsis secondary to intra-abdominal infection. Shock. 2005;23:400–405. doi: 10.1097/01.shk.0000159930.87737.8a.
- Nakamura T, Ebihara I, Shimada N, Koide H. Changes in plasma erythropoietin and interleukin-6 concentrations in patients with septic shock after hemoperfusion with polymyxin B-immobilized fiber. Intensive Care Med. 1998;24:1272–1276. doi: 10.1007/s001340050761.
- Cruz DN, Ronco C. Acute kidney injury in the intensive care unit: current trends in incidence and outcome. Crit Care. 2007;11:149. doi: 10.1186/cc5965.
- Nakamura T, Kawagoe Y, Matsuda T, Ueda Y, Koide H. Effects of polymyxin B immobilized fiber on urinary N-acetyl-beta-glucosaminidase in patients with severe sepsis. ASAIO J. 2004;50:563–567. doi: 10.1097/01.MAT.0000142875.62592.3A.
- Wesche-Soldato DE, Swan RZ, Chung CS, Ayala A. The apoptotic pathway as a therapeutic target in sepsis. Curr Drug Targets. 2007;8:493–500. doi: 10.2174/138945007780362764.
- Kang YH, Falk MC, Bentley TB, Lee CH. Distribution and role of lipopolysaccharide in the pathogenesis of acute renal proximal tubule injury. Shock. 1995;4:441–449.
- Bordoni V, Bolgan I, Brendolan A, Crepaldi C, Gastaldon F, D’Intini V, Pilotto L, Inguaggiato P, Bonello M, Galloni E, Everard P, Bellomo R, Ronco C. Caspase-3 and -8 activation and cytokine removal with a novel cellulose triacetate super-permeable membrane in an in vitro sepsis model. Int J Artif Organs. 2003;26:897–905.
- Ayala A, Herdon CD, Lehman DL, DeMaso CM, Ayala CA, Chaudry IH. The induction of accelerated thymic programmed cell death during polymicrobial sepsis: control by corticosteroids but not tumor necrosis factor. Shock. 1995;3:259–267. doi: 10.1097/00024382-199504000-00003.
- Crouser ED, Julian MW, Weinstein DM, Fahy RJ, Bauer JA. Endotoxin-induced ileal mucosal injury and nitric oxide dysregulation are temporally dissociated. Am J Respir Crit Care Med. 2000;161:1705–1712.
- Camussi G, Mariano F, Biancone L, De Martino A, Bussolati B, Montrucchio G, Tobias PS. Lipopolysaccharide binding protein and CD14 modulate the synthesis of platelet-activating factor by human monocytes and mesangial and endothelial cells stimulated with lipopolysaccharide. J Immunol. 1995;155:316–324.
- Imai Y, Parodo J, Kajikawa O, de Perrot M, Fischer S, Edwards V, Cutz E, Liu M, Keshavjee S, Martin TR, Marshall JC, Ranieri VM, Slutsky AS. Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome. JAMA. 2003;289:2104–2112. doi: 10.1001/jama.289.16.2104.
- Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;348:138–150. doi: 10.1056/NEJMra021333.
- Pasero D CV, Assenzio B, Puntorieri V, Mascia L, Ranieri VM. Hemoperfusion with Polymyxin-B Cartridge protecs from sepsis-related acute kidney injury. Intensive Care Med. 2006;32:S224.
- Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med. 2003;29:530–538.
- Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ., Jr Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344:699–709. doi: 10.1056/NEJM200103083441001.
- Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858–873. doi: 10.1097/01.CCM.0000117317.18092.E4.
- Moreno R, Vincent JL, Matos R, Mendonca A, Cantraine F, Thijs L, Takala J, Sprung C, Antonelli M, Bruining H, Willatts S. The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis related Problems of the ESICM. Intensive Care Med. 1999;25:686–696. doi: 10.1007/s001340050931.
- Bellomo R, Kellum JA, Ronco C. Defining and classifying acute renal failure: from advocacy to consensus and validation of the RIFLE criteria. Intensive Care Med. 2007;33:409–413. doi: 10.1007/s00134-006-0478-x.
- Xin G, Wang M, Jiao LL, Xu GB, Wang HY. Protein-to-creatinine ratio in spot urine samples as a predictor of quantitation of proteinuria. Clin Chim Acta. 2004;350:35–39. doi: 10.1016/j.cccn.2004.06.019.
- Conaldi PG, Bottelli A, Baj A, Serra C, Fiore L, Federico G, Bussolati B, Camussi G. Human immunodeficiency virus-1 tat induces hyperproliferation and dysregulation of renal glomerular epithelial cells. Am J Pathol. 2002;161:53–61.
- Conaldi PG, Biancone L, Bottelli A, Wade-Evans A, Racusen LC, Boccellino M, Orlandi V, Serra C, Camussi G, Toniolo A. HIV-1 kills renal tubular epithelial cells in vitro by triggering an apoptotic pathway involving caspase activation and Fas upregulation. J Clin Invest. 1998;102:2041–2049. doi: 10.1172/JCI3480.
- Biancone L, Cantaluppi V, Segoloni G, Boccellino M, Del Sorbo L, Conaldi PG, Tjoelker LW, Maruyama S, Cantu E, Stern D, Andres G, Camussi G. Role of platelet-activating factor in functional alterations induced by xenoreactive antibodies in porcine endothelial cells. Transplantation. 2000;70:1198–1205. doi: 10.1097/00007890-200010270-00013.
- Glynne PA, Picot J, Evans TJ. Coexpressed nitric oxide synthase and apical beta(1) integrins influence tubule cell adhesion after cytokine-induced injury. J Am Soc Nephrol. 2001;12:2370–2383.
- Reiser J, von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L, Rastaldi MP, Calvaresi N, Watanabe H, Schwarz K, Faul C, Kretzler M, Davidson A, Sugimoto H, Kalluri R, Sharpe AH, Kreidberg JA, Mundel P. Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest. 2004;113:1390–1397.
- Nemoto H, Nakamoto H, Okada H, Sugahara S, Moriwaki K, Arai M, Kanno Y, Suzuki H. Newly developed immobilized polymyxin B fibers improve the survival of patients with sepsis. Blood Purif. 2001;19:361–368. doi: 10.1159/000046966.
- Wan L, Bellomo R, Di Giantomasso D, Ronco C. The pathogenesis of septic acute renal failure. Curr Opin Crit Care. 2003;9:496–502. doi: 10.1097/00075198-200312000-00006.
- Trof RJ, Di Maggio F, Leemreis J, Groeneveld AB. Biomarkers of acute renal injury and renal failure. Shock. 2006;26:245–253. doi: 10.1097/01.shk.0000225415.5969694.ce.
- Tryggvason K, Patrakka J, Wartiovaara J. Hereditary proteinuria syndromes and mechanisms of proteinuria. N Engl J Med. 2006;354:1387–1401. doi: 10.1056/NEJMra052131.
- Christensen EI, Birn H. Megalin and cubilin: synergistic endocytic receptors in renal proximal tubule. Am J Physiol Renal Physiol. 2001;280:F562–573.
- De Gaudio AR, Adembri C, Grechi S, Novelli GP. Microalbuminuria as an early index of impairment of glomerular permeability in postoperative septic patients. Intensive Care Med. 2000;26:1364–1368. doi: 10.1007/s001340000593.
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