Protective Effect of Resin Adsorption on Septic Plasma-induced Tubular Injury

Overview

Journal Crit Care

Specialty Critical Care

Date 2010 Jan 13

PMID 20064258

Citations 21

Authors

Vincenzo Cantaluppi

Viktoria Weber

Carola Lauritano

Federico Figliolini

Silvia Beltramo

Luigi Biancone

Massimo De Cal

Dinna Cruz

Claudio Ronco

Giuseppe Paolo Segoloni

Ciro Tetta

Giovanni Camussi

Affiliations

Soon will be listed here.

Abstract

Introduction: A pro-apoptotic effect of circulating mediators on renal tubular epithelial cells has been involved in the pathogenesis of sepsis-associated acute kidney injury (AKI). Adsorption techniques have been showed to efficiently remove inflammatory cytokines from plasma. The aim of this study was to evaluate the efficiency of the hydrophobic resin Amberchrom CG161 M to adsorb from septic plasma soluble mediators involved in tubular injury.

Methods: We enrolled in the study 10 critically ill patients with sepsis-associated AKI and we evaluated the effects of their plasma on granulocyte adhesion, apoptosis and functional alterations of cultured human kidney tubular epithelial cells. We established an in vitro model of plasma adsorption and we studied the protective effect of unselective removal of soluble mediators by the Amberchrom CG161 M resin on septic plasma-induced tubular cell injury.

Results: Plasma from septic patients induced granulocyte adhesion, apoptosis and altered polarity in tubular cells. Plasma adsorption significantly decreased these effects and abated the concentrations of several soluble mediators. The inhibition of granulocyte adhesion to tubular cells was associated with the down-regulation of ICAM-1 and CD40. Resin adsorption inhibited tubular cell apoptosis induced by septic plasma by down-regulating the activation of caspase-3, 8, 9 and of Fas/death receptor-mediated signalling pathways. The alteration of cell polarity, morphogenesis, protein reabsorption and the down-regulation of the tight junction molecule ZO-1, of the sodium transporter NHE3, of the glucose transporter GLUT-2 and of the endocytic receptor megalin all induced by septic plasma were significantly reduced by resin adsorption.

Conclusions: Septic plasma induced a direct injury of tubular cells by favouring granulocyte adhesion, by inducing cell apoptosis and by altering cell polarity and function. All these biological effects are related to the presence of circulating inflammatory mediators that can be efficiently removed by resin adsorption with a consequent limitation of tubular cell injury.

Citing Articles

High-volume hemofiltration does not protect human kidney endothelial and tubular epithelial cells from septic plasma-induced injury.

Medica D, Quercia A, Marengo M, Fanelli V, Castellano G, Fabbrini P Sci Rep. 2024; 14(1):18323.

PMID: 39112634 PMC: 11306637. DOI: 10.1038/s41598-024-69202-z.

Extracorporeal blood purification therapies for sepsis-associated acute kidney injury in critically ill patients: expert opinion from the SIAARTI-SIN joint commission.

De Rosa S, Marengo M, Fiorentino M, Fanelli V, Brienza N, Fiaccadori E J Nephrol. 2023; 36(7):1731-1742.

PMID: 37439963 PMC: 10543830. DOI: 10.1007/s40620-023-01637-5.

Cellular Immuno-Profile in Septic Human Host: A Scoping Review.

Zanza C, Caputo G, Tornatore G, Romenskaya T, Piccioni A, Franceschi F Biology (Basel). 2022; 11(11).

PMID: 36358327 PMC: 9687154. DOI: 10.3390/biology11111626.

Kynurenine Pathway-An Underestimated Factor Modulating Innate Immunity in Sepsis-Induced Acute Kidney Injury?.

Krupa A, Krupa M, Pawlak K Cells. 2022; 11(16).

PMID: 36010680 PMC: 9406744. DOI: 10.3390/cells11162604.

Acute Tubular Injury is Associated With Severe Traumatic Brain Injury: in Vitro Study on Human Tubular Epithelial Cells.

Civiletti F, Assenzio B, Mazzeo A, Medica D, Giaretta F, Deambrosis I Sci Rep. 2019; 9(1):6090.

PMID: 30988316 PMC: 6465296. DOI: 10.1038/s41598-019-42147-4.

References

Schmidt C, Hocherl K, Bucher M . Cytokine-mediated regulation of urea transporters during experimental endotoxemia. Am J Physiol Renal Physiol. 2007; 292(5):F1479-89. DOI: 10.1152/ajprenal.00460.2006. View

Han X, Fink M, Uchiyama T, Yang R, Delude R . Increased iNOS activity is essential for hepatic epithelial tight junction dysfunction in endotoxemic mice. Am J Physiol Gastrointest Liver Physiol. 2003; 286(1):G126-36. DOI: 10.1152/ajpgi.00231.2003. View

Kellum J, Johnson J, Kramer D, Palevsky P, Brady J, Pinsky M . Diffusive vs. convective therapy: effects on mediators of inflammation in patient with severe systemic inflammatory response syndrome. Crit Care Med. 1999; 26(12):1995-2000. DOI: 10.1097/00003246-199812000-00027. View

Molnar Z, Szakmany T, Heigl P . Microalbuminuria does not reflect increased systemic capillary permeability in septic shock. Intensive Care Med. 2003; 29(3):391-5. DOI: 10.1007/s00134-003-1651-0. View

Wan L, Bellomo R, Di Giantomasso D, Ronco C . The pathogenesis of septic acute renal failure. Curr Opin Crit Care. 2003; 9(6):496-502. DOI: 10.1097/00075198-200312000-00006. View

Montrucchio G, Lupia E, De Martino A, Silvestro L, Savu S, Cacace G . Plasmin promotes an endothelium-dependent adhesion of neutrophils. Involvement of platelet activating factor and P-selectin. Circulation. 1996; 93(12):2152-60. DOI: 10.1161/01.cir.93.12.2152. View

Kellum J, Song M, Venkataraman R . Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-kappaB DNA binding, and improves short-term survival in lethal endotoxemia. Crit Care Med. 2004; 32(3):801-5. DOI: 10.1097/01.ccm.0000114997.39857.69. View

Ronco C, Tetta C, Mariano F, Wratten M, Bonello M, Bordoni V . Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis. Artif Organs. 2003; 27(9):792-801. DOI: 10.1046/j.1525-1594.2003.07289.x. View

Schrier R, Wang W . Acute renal failure and sepsis. N Engl J Med. 2004; 351(2):159-69. DOI: 10.1056/NEJMra032401. View

10.

Cantaluppi V, Biancone L, Romanazzi G, Figliolini F, Beltramo S, Galimi F . Macrophage stimulating protein may promote tubular regeneration after acute injury. J Am Soc Nephrol. 2008; 19(10):1904-18. PMC: 2551565. DOI: 10.1681/ASN.2007111209. View

11.

Jo S, Cha D, Cho W, Kim H, Chang K, Yun S . Inflammatory cytokines and lipopolysaccharide induce Fas-mediated apoptosis in renal tubular cells. Nephron. 2002; 91(3):406-15. DOI: 10.1159/000064280. View

12.

Zanotti-Cavazzoni S, Hollenberg S . Cardiac dysfunction in severe sepsis and septic shock. Curr Opin Crit Care. 2009; 15(5):392-7. DOI: 10.1097/MCC.0b013e3283307a4e. View

13.

Stromberg P, Woolsey C, Clark A, Clark J, Turnbull I, McConnell K . CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis. FASEB J. 2009; 23(6):1817-25. PMC: 2698654. DOI: 10.1096/fj.08-119024. View

14.

van Kooten C, Woltman A, Daha M . Immunological function of tubular epithelial cells: the functional implications of CD40 expression. Exp Nephrol. 2000; 8(4-5):203-7. DOI: 10.1159/000020669. View

15.

Christensen E, Birn H . Megalin and cubilin: synergistic endocytic receptors in renal proximal tubule. Am J Physiol Renal Physiol. 2001; 280(4):F562-73. DOI: 10.1152/ajprenal.2001.280.4.F562. View

16.

Guo R, Wang Y, Minto A, Quigg R, Cunningham P . Acute renal failure in endotoxemia is dependent on caspase activation. J Am Soc Nephrol. 2004; 15(12):3093-102. DOI: 10.1097/01.ASN.0000145530.73247.F5. View

17.

Fink M, Delude R . Epithelial barrier dysfunction: a unifying theme to explain the pathogenesis of multiple organ dysfunction at the cellular level. Crit Care Clin. 2005; 21(2):177-96. DOI: 10.1016/j.ccc.2005.01.005. View

18.

Klenzak J, Himmelfarb J . Sepsis and the kidney. Crit Care Clin. 2005; 21(2):211-22. DOI: 10.1016/j.ccc.2005.01.002. View

19.

Tetta C, Gianotti L, Cavaillon J, Wratten M, Fini M, Braga M . Coupled plasma filtration-adsorption in a rabbit model of endotoxic shock. Crit Care Med. 2000; 28(5):1526-33. DOI: 10.1097/00003246-200005000-00045. View

20.

Inwald D, Faust S, Lister P, Peters M, Levin M, Heyderman R . Platelet and soluble CD40L in meningococcal sepsis. Intensive Care Med. 2006; 32(9):1432-7. DOI: 10.1007/s00134-006-0250-2. View