Letter to the Editor Published online: October 17, 2014
Blood Purif 2014;38:100–101 DOI: 10.1159/000363496
Is Procalcitonin Reduction Indicative of Immunomodulation in Septic Patients Treated with Hemodialysis with High Cutoff Membrane? Gianluca Villa Paola Di Maggio A. Raffaele De Gaudio Section of Anesthesiology and Intensive Care, Department of Health Science, University of Florence, Florence, Italy
to an anti-inflammatory effect of the procedure. In fact, in a previous observational study in patients with severe sepsis and acute kidney injury [5], high concentrations of PCT were constantly found in the dialysate fluid and a constant sieving coefficient of about 50% for PCT was observed during hemodialysis with a 60-kDa cutoff membrane (SepteX). In this scenario, Creactive protein, rather than PCT, may serve as an alternative sepsis biomarker, given that the higher molecular weight of C-reactive protein of 115 kDa [6] will prevent its filtration through the pores of high cutoff membranes. Certainly, in the paper referred to above [1] the decrease in the PCT serum level during treatment is possibly linked to the reduction of the endotoxin activity assay or to the neutralization of the infective stimuli by appropriate antibacterial therapies or by source control. However, the single contribution of each factor cannot be established and a direct diffusion of the molecules through the membrane cannot be excluded. Moreover, lipopolysaccharides as well as proinflammatory cytokines, released in the presence of microbial components, are the main stimuli for CALC-1 gene expression, which is responsible for the increase in serum PCT levels during in-
© 2014 S. Karger AG, Basel 0253–5068/14/0382–0100$39.50/0 E-Mail [email protected] www.karger.com/bpu
fection [3]. Considering that high levels of proinflammatory cytokines were observed during treatment [1], it could be assumed that cytokine-mediated PCT production was still maintained, and that the observed reduction in PCT serum concentration was a result of PCT diffusion through the high cutoff membrane. However, considering the pathophysiological role of PCT in sepsis, it can be speculated that active PCT removal from the circulation by HCO-CVVHD could have a therapeutic effect. Indeed, PCT is a proinflammatory chemokine [7, 8], it increases vasorelaxation inducing NO synthase [9] and, in experimental models, PCT infusion decreases renal function and cardiovascular stability [10]. Therefore, PCT active removal by filtration techniques may be beneficial. Finally, according to the conclusion reported by Yaroustovsky et al. [1], a positive effect of the combined extracorporeal therapy on restoring the immune homeostasis could be shown in septic patients. However, the observed reduction of serum PCT levels may not be the sole result of the antibacterial therapy, but plausibly the consequence of PCT elimination through the membrane.
Gianluca Villa Section of Anesthesiology and Intensive Care, Department of Health Science University of Florence, Largo Brambilla 3 IT–50134 Florence (Italy) E-Mail gianlucavilla1 @ gmail.com
Downloaded by: UCSF Library & CKM 128.218.166.245 - 5/13/2015 11:21:24 PM
Dear Editor, I read with great interest the article published in your journal by Yaroustovsky et al. [1] regarding the beneficial effects of combining hemodialysis with high cutoff membranes (continuous venovenous hemodiafiltration with high cutoff membranes, HCO-CVVHD) and lipopolysaccharide adsorption in cardiac surgery patients with severe sepsis. The authors reported that the benefits of using extracorporeal therapies were demonstrated by several changes in the parameters analyzed, including the reduction of procalcitonin (PCT) during treatment. Since PCT is released in the plasma during the acute phase response to infections [2], it is generally considered a reliable biomarker of bacterial sepsis [3] and may be conveniently used to monitor the efficacy of antibacterial therapy [4]. However, its clinical value as a biomarker could be less meaningful in cases of patients treated with a blood purification therapy, in particular with HCO-CVVHD, given that the molecular weight of PCT is about 13 kDa, a value which is below the cutoff of membranes. In the study of Yaroustovsky et al. [1], the observed reduction of PCT plasma concentration could be mainly due to the direct diffusion of PCT through the membrane pores (EMiC2, cutoff 40 kDa), rather than
References
PCT during High Cutoff Membrane Hemodialysis
5 Caldini A, Chelazzi C, Terreni A, Biagioli T, Giannoni C, Villa G, Messeri G, De Gaudio AR: Is procalcitonin a reliable marker of sepsis in critically ill septic patients undergoing continuous veno-venous hemodiafiltration with ‘high cut-off’ membranes (HCO-CVVHDF)? Clin Chem Lab Med 2013;51:e261–e263. 6 Honoré PM, Matson JR: Hemofiltration, adsorption, sieving and the challenge of sepsis therapy design. Crit Care 2002;6:394–396. 7 Wiedermann FJ, Kaneider N, Egger P, Tiefenthaler W, Wiedermann CJ, Lindner KH, Schobersberger W: Migration of human monocytes in response to procalcitonin. Crit Care Med 2002;30:1112–1117.
8 Whang KT, Vath SD, Becker KL, Snider RH, Nylen ES, Muller B, Li Q, Tamarkin L, White JC: Procalcitonin and proinflammatory cytokine interactions in sepsis. Shock 2000;14:73– 78. 9 Hoffmann G, Czechowski M, Schloesser M, Schobersberger W: Procalcitonin amplifies inducible nitric oxide synthase gene expression and nitric oxide production in vascular smooth muscle cells. Crit Care Med 2002; 30: 2091–2095. 10 Becker KL, Nylén ES, Snider RH, Müller B, White JC: Immunoneutralization of procalcitonin as therapy of sepsis. J Endotoxin Res 2003;9:367–374.
Blood Purif 2014;38:100–101 DOI: 10.1159/000363496
101
Downloaded by: UCSF Library & CKM 128.218.166.245 - 5/13/2015 11:21:24 PM
1 Yaroustovsky M, Abramyan M, Krotenko N, Popov D, Plyushch M, Rogalskaya E, Nazarova H: Combined extracorporeal therapy for severe sepsis in patients after cardiac surgery. Blood Purif 2014;37:39–46. 2 Lim KS: The usefulness of procalcitonin and C-reactive protein as early diagnostic markers of bacteremia in cancer patients with febrile neutropenia. Cancer Res Treat 2011; 43: 176– 180. 3 Riedel S: Procalcitonin and the role of biomarkers in the diagnosis and management of sepsis. Diagn Microbiol Infect Dis 2012; 73: 221–227. 4 Schuetz P, Albrich W, Mueller B: Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future. BMC Med 2011;9:107.
Blood Purif 2014;38:100–101 DOI: 10.1159/000363496
Is Procalcitonin Reduction Indicative of Immunomodulation in Septic Patients Treated with Hemodialysis with High Cutoff Membrane? Gianluca Villa Paola Di Maggio A. Raffaele De Gaudio Section of Anesthesiology and Intensive Care, Department of Health Science, University of Florence, Florence, Italy
to an anti-inflammatory effect of the procedure. In fact, in a previous observational study in patients with severe sepsis and acute kidney injury [5], high concentrations of PCT were constantly found in the dialysate fluid and a constant sieving coefficient of about 50% for PCT was observed during hemodialysis with a 60-kDa cutoff membrane (SepteX). In this scenario, Creactive protein, rather than PCT, may serve as an alternative sepsis biomarker, given that the higher molecular weight of C-reactive protein of 115 kDa [6] will prevent its filtration through the pores of high cutoff membranes. Certainly, in the paper referred to above [1] the decrease in the PCT serum level during treatment is possibly linked to the reduction of the endotoxin activity assay or to the neutralization of the infective stimuli by appropriate antibacterial therapies or by source control. However, the single contribution of each factor cannot be established and a direct diffusion of the molecules through the membrane cannot be excluded. Moreover, lipopolysaccharides as well as proinflammatory cytokines, released in the presence of microbial components, are the main stimuli for CALC-1 gene expression, which is responsible for the increase in serum PCT levels during in-
© 2014 S. Karger AG, Basel 0253–5068/14/0382–0100$39.50/0 E-Mail [email protected] www.karger.com/bpu
fection [3]. Considering that high levels of proinflammatory cytokines were observed during treatment [1], it could be assumed that cytokine-mediated PCT production was still maintained, and that the observed reduction in PCT serum concentration was a result of PCT diffusion through the high cutoff membrane. However, considering the pathophysiological role of PCT in sepsis, it can be speculated that active PCT removal from the circulation by HCO-CVVHD could have a therapeutic effect. Indeed, PCT is a proinflammatory chemokine [7, 8], it increases vasorelaxation inducing NO synthase [9] and, in experimental models, PCT infusion decreases renal function and cardiovascular stability [10]. Therefore, PCT active removal by filtration techniques may be beneficial. Finally, according to the conclusion reported by Yaroustovsky et al. [1], a positive effect of the combined extracorporeal therapy on restoring the immune homeostasis could be shown in septic patients. However, the observed reduction of serum PCT levels may not be the sole result of the antibacterial therapy, but plausibly the consequence of PCT elimination through the membrane.
Gianluca Villa Section of Anesthesiology and Intensive Care, Department of Health Science University of Florence, Largo Brambilla 3 IT–50134 Florence (Italy) E-Mail gianlucavilla1 @ gmail.com
Downloaded by: UCSF Library & CKM 128.218.166.245 - 5/13/2015 11:21:24 PM
Dear Editor, I read with great interest the article published in your journal by Yaroustovsky et al. [1] regarding the beneficial effects of combining hemodialysis with high cutoff membranes (continuous venovenous hemodiafiltration with high cutoff membranes, HCO-CVVHD) and lipopolysaccharide adsorption in cardiac surgery patients with severe sepsis. The authors reported that the benefits of using extracorporeal therapies were demonstrated by several changes in the parameters analyzed, including the reduction of procalcitonin (PCT) during treatment. Since PCT is released in the plasma during the acute phase response to infections [2], it is generally considered a reliable biomarker of bacterial sepsis [3] and may be conveniently used to monitor the efficacy of antibacterial therapy [4]. However, its clinical value as a biomarker could be less meaningful in cases of patients treated with a blood purification therapy, in particular with HCO-CVVHD, given that the molecular weight of PCT is about 13 kDa, a value which is below the cutoff of membranes. In the study of Yaroustovsky et al. [1], the observed reduction of PCT plasma concentration could be mainly due to the direct diffusion of PCT through the membrane pores (EMiC2, cutoff 40 kDa), rather than
References
PCT during High Cutoff Membrane Hemodialysis
5 Caldini A, Chelazzi C, Terreni A, Biagioli T, Giannoni C, Villa G, Messeri G, De Gaudio AR: Is procalcitonin a reliable marker of sepsis in critically ill septic patients undergoing continuous veno-venous hemodiafiltration with ‘high cut-off’ membranes (HCO-CVVHDF)? Clin Chem Lab Med 2013;51:e261–e263. 6 Honoré PM, Matson JR: Hemofiltration, adsorption, sieving and the challenge of sepsis therapy design. Crit Care 2002;6:394–396. 7 Wiedermann FJ, Kaneider N, Egger P, Tiefenthaler W, Wiedermann CJ, Lindner KH, Schobersberger W: Migration of human monocytes in response to procalcitonin. Crit Care Med 2002;30:1112–1117.
8 Whang KT, Vath SD, Becker KL, Snider RH, Nylen ES, Muller B, Li Q, Tamarkin L, White JC: Procalcitonin and proinflammatory cytokine interactions in sepsis. Shock 2000;14:73– 78. 9 Hoffmann G, Czechowski M, Schloesser M, Schobersberger W: Procalcitonin amplifies inducible nitric oxide synthase gene expression and nitric oxide production in vascular smooth muscle cells. Crit Care Med 2002; 30: 2091–2095. 10 Becker KL, Nylén ES, Snider RH, Müller B, White JC: Immunoneutralization of procalcitonin as therapy of sepsis. J Endotoxin Res 2003;9:367–374.
Blood Purif 2014;38:100–101 DOI: 10.1159/000363496
101
Downloaded by: UCSF Library & CKM 128.218.166.245 - 5/13/2015 11:21:24 PM
1 Yaroustovsky M, Abramyan M, Krotenko N, Popov D, Plyushch M, Rogalskaya E, Nazarova H: Combined extracorporeal therapy for severe sepsis in patients after cardiac surgery. Blood Purif 2014;37:39–46. 2 Lim KS: The usefulness of procalcitonin and C-reactive protein as early diagnostic markers of bacteremia in cancer patients with febrile neutropenia. Cancer Res Treat 2011; 43: 176– 180. 3 Riedel S: Procalcitonin and the role of biomarkers in the diagnosis and management of sepsis. Diagn Microbiol Infect Dis 2012; 73: 221–227. 4 Schuetz P, Albrich W, Mueller B: Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future. BMC Med 2011;9:107.
