Skip to main content
Top
Published in: Intensive Care Medicine 5/2013

01-05-2013 | Pediatric Original

Peri-operative interventions, but not inflammatory mediators, increase risk of acute kidney injury after cardiac surgery: a prospective cohort study

Authors: Catherine J. Morgan, Peter J. Gill, Simon Lam, Ari R. Joffe

Published in: Intensive Care Medicine | Issue 5/2013

Login to get access

Abstract

Purpose

Cardiopulmonary bypass (CPB)-related inflammatory response might be one mechanism by which cardiac surgery associated acute kidney injury (CS-AKI) occurs. Interventions that may attenuate inflammation, including glucocorticoids or phosphodiesterase inhibitors, could therefore have a role in its prevention. We aimed to determine the role of inflammatory mediators in CS-AKI in children and the efficacy of commonly used peri-operative interventions to reduce CS-AKI risk.

Methods

We prospectively studied 109 children undergoing heart surgery. Using regression modeling (adjusting for covariates), we (1) evaluated the association between inflammatory mediators [interleukin (IL)-6, IL-8, C-reactive protein, and tumor necrosis factor-α levels] and CS-AKI, and (2) evaluated risk/prevention factors for CS-AKI including glucocorticoid and milrinone administration. CS-AKI was defined based on pRIFLE methods.

Results

CS-AKI occurred in 68 % of children. No inflammatory mediator measured had an independent association with CS-AKI. Higher pre-operative glomerular filtration rate (GFR), sustained decrease in mean arterial pressure during CPB, post-operative single ventricle physiology, deep hypothermic circulatory arrest, and milrinone use at 24 h post-operatively were significant independent predictors of CS-AKI. Intra-operative steroid administration had no effect on the rate of CS-AKI.

Conclusions

Although inflammatory mediators are up-regulated following CPB, we found no association between levels of inflammatory cytokines and CS-AKI. CS-AKI has complex pathophysiology and the observation that milrinone was associated with increased AKI risk (and that higher GFR predicts more injury) suggests that mechanisms beyond inflammation play a significant role. Intra-operative administration of glucocorticoid does not appear to be an effective intervention for reducing the risk of CS-AKI.
Literature
2.
go back to reference Zappitelli M, Moffett BS, Hyder A, Goldstein SL (2011) Acute kidney injury in non-critically ill children treated with aminoglycoside antibiotics in a tertiary healthcare centre: a retrospective cohort study. Nephrol Dial Transpl 26:144–150. doi:10.1093/ndt/gfq375 CrossRef Zappitelli M, Moffett BS, Hyder A, Goldstein SL (2011) Acute kidney injury in non-critically ill children treated with aminoglycoside antibiotics in a tertiary healthcare centre: a retrospective cohort study. Nephrol Dial Transpl 26:144–150. doi:10.​1093/​ndt/​gfq375 CrossRef
4.
go back to reference Schneider J, Khemani R, Grushkin C, Bart R (2010) Serum creatinine as stratified in the RIFLE score for acute kidney injury is associated with mortality and length of stay for children in the pediatric intensive care unit. Crit Care Med 38:933–939. doi:10.1097/CCM.0b013e3181cd12e1 PubMedCrossRef Schneider J, Khemani R, Grushkin C, Bart R (2010) Serum creatinine as stratified in the RIFLE score for acute kidney injury is associated with mortality and length of stay for children in the pediatric intensive care unit. Crit Care Med 38:933–939. doi:10.​1097/​CCM.​0b013e3181cd12e1​ PubMedCrossRef
8.
go back to reference Kalfin RE, Engelman RM, Rousou JA, Flack JE 3rd, Deaton DW, Kreutzer DL, Das DK (1993) Induction of interleukin-8 expression during cardiopulmonary bypass. Circulation 88:II401–II406PubMed Kalfin RE, Engelman RM, Rousou JA, Flack JE 3rd, Deaton DW, Kreutzer DL, Das DK (1993) Induction of interleukin-8 expression during cardiopulmonary bypass. Circulation 88:II401–II406PubMed
9.
go back to reference Finn A, Naik S, Klein N, Levinsky RJ, Strobel S, Elliott M (1993) Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass. J Thorac Cardiovasc Surg 105:234–241PubMed Finn A, Naik S, Klein N, Levinsky RJ, Strobel S, Elliott M (1993) Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass. J Thorac Cardiovasc Surg 105:234–241PubMed
12.
13.
14.
go back to reference Wernovsky G, Wypij D, Jonas RA et al (1995) Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation 92:2226–2235. doi:10.1161/01.CIR.92.8.2226 PubMedCrossRef Wernovsky G, Wypij D, Jonas RA et al (1995) Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation 92:2226–2235. doi:10.​1161/​01.​CIR.​92.​8.​2226 PubMedCrossRef
15.
go back to reference Aronen M, Leijala M, Meri S (1990) Value of C-reactive protein in reflecting the magnitude of complement activation in children undergoing open heart surgery. Intensive Care Med 16:128–132. doi:10.1007/BF02575308 PubMedCrossRef Aronen M, Leijala M, Meri S (1990) Value of C-reactive protein in reflecting the magnitude of complement activation in children undergoing open heart surgery. Intensive Care Med 16:128–132. doi:10.​1007/​BF02575308 PubMedCrossRef
16.
go back to reference Butler J, Parker D, Pillai R, Westaby S, Shale DJ, Rocker GM (1993) Effect of cardiopulmonary bypass on systemic release of neutrophil elastase and tumor necrosis factor. J Thorac Cardiovasc Surg 105:25–30PubMed Butler J, Parker D, Pillai R, Westaby S, Shale DJ, Rocker GM (1993) Effect of cardiopulmonary bypass on systemic release of neutrophil elastase and tumor necrosis factor. J Thorac Cardiovasc Surg 105:25–30PubMed
17.
go back to reference Chew MS, Brandslund I, Brix-Christensen V et al (2001) Tissue injury and the inflammatory response to pediatric cardiac surgery with cardiopulmonary bypass: a descriptive study. Anesthesiology 94:745–753PubMedCrossRef Chew MS, Brandslund I, Brix-Christensen V et al (2001) Tissue injury and the inflammatory response to pediatric cardiac surgery with cardiopulmonary bypass: a descriptive study. Anesthesiology 94:745–753PubMedCrossRef
18.
go back to reference el-Barbary M, Khabar KS (2002) Soluble tumor necrosis factor receptor p55 predicts cytokinemia and systemic inflammatory response after cardiopulmonary bypass. Crit Care Med 30:1712–1716PubMedCrossRef el-Barbary M, Khabar KS (2002) Soluble tumor necrosis factor receptor p55 predicts cytokinemia and systemic inflammatory response after cardiopulmonary bypass. Crit Care Med 30:1712–1716PubMedCrossRef
19.
go back to reference Hirai S, Sueda T, Orihashi K, Watari M, Okada K (2001) Kinetics of pro-inflammatory cytokines release in cardiac surgery with cardiopulmonary bypass. Jpn J Thorac Cardiovasc Surg 49:216–219. doi:10.1007/BF02913518 PubMedCrossRef Hirai S, Sueda T, Orihashi K, Watari M, Okada K (2001) Kinetics of pro-inflammatory cytokines release in cardiac surgery with cardiopulmonary bypass. Jpn J Thorac Cardiovasc Surg 49:216–219. doi:10.​1007/​BF02913518 PubMedCrossRef
24.
go back to reference Alkandari O, Eddington KA, Hyder A et al (2011) Acute kidney injury is an independent risk factor for pediatric intensive care unit mortality, longer length of stay and prolonged mechanical ventilation in critically ill children: a two-center retrospective cohort study. Crit Care 15:R146. doi:10.1186/cc10269 PubMedCrossRef Alkandari O, Eddington KA, Hyder A et al (2011) Acute kidney injury is an independent risk factor for pediatric intensive care unit mortality, longer length of stay and prolonged mechanical ventilation in critically ill children: a two-center retrospective cohort study. Crit Care 15:R146. doi:10.​1186/​cc10269 PubMedCrossRef
25.
go back to reference Mickey RM, Greenland S (1989) The impact of confounder selection criteria on effect estimation. Am J Epidemiol 129:125–137PubMed Mickey RM, Greenland S (1989) The impact of confounder selection criteria on effect estimation. Am J Epidemiol 129:125–137PubMed
29.
go back to reference Skippen PW, Krahn GE (2005) Acute renal failure in children undergoing cardiopulmonary bypass. Crit Care Resusc 7:286–291PubMed Skippen PW, Krahn GE (2005) Acute renal failure in children undergoing cardiopulmonary bypass. Crit Care Resusc 7:286–291PubMed
30.
go back to reference Liu KD, Altmann C, Smits G, Krawczeski CD, Edelstein CL, Devarajan P, Faubel S (2009) Serum interleukin-6 and interleukin-8 are early biomarkers of acute kidney injury and predict prolonged mechanical ventilation in children undergoing cardiac surgery: a case-control study. Crit Care 13:R104. doi:10.1186/cc7940 PubMedCrossRef Liu KD, Altmann C, Smits G, Krawczeski CD, Edelstein CL, Devarajan P, Faubel S (2009) Serum interleukin-6 and interleukin-8 are early biomarkers of acute kidney injury and predict prolonged mechanical ventilation in children undergoing cardiac surgery: a case-control study. Crit Care 13:R104. doi:10.​1186/​cc7940 PubMedCrossRef
31.
go back to reference Morgan CJ, Zappitelli M, Robertson CM, et al. (2012) Risk factors for and outcomes of acute kidney injury in neonates undergoing complex cardiac surgery. J Pediatr. doi:10.1016/j.jpeds.2012.06.054 (Epub ahead of print) Morgan CJ, Zappitelli M, Robertson CM, et al. (2012) Risk factors for and outcomes of acute kidney injury in neonates undergoing complex cardiac surgery. J Pediatr. doi:10.​1016/​j.​jpeds.​2012.​06.​054 (Epub ahead of print)
33.
go back to reference Dennen P, Altmann C, Kaufman J et al (2010) Urine interleukin-6 is an early biomarker of acute kidney injury in children undergoing cardiac surgery. Crit Care 14:R181. doi:10.1186/cc9289 PubMedCrossRef Dennen P, Altmann C, Kaufman J et al (2010) Urine interleukin-6 is an early biomarker of acute kidney injury in children undergoing cardiac surgery. Crit Care 14:R181. doi:10.​1186/​cc9289 PubMedCrossRef
34.
36.
39.
go back to reference Park KM, Chen A, Bonventre JV (2001) Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment. J Biol Chem 276:11870–11876. doi:10.1074/jbc.M007518200 PubMedCrossRef Park KM, Chen A, Bonventre JV (2001) Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment. J Biol Chem 276:11870–11876. doi:10.​1074/​jbc.​M007518200 PubMedCrossRef
41.
go back to reference Redfors B, Sward K, Sellgren J, Ricksten SE (2009) Effects of mannitol alone and mannitol plus furosemide on renal oxygen consumption, blood flow and glomerular filtration after cardiac surgery. Intensive Care Med 35:115–122. doi:10.1007/s00134-008-1206-5 PubMedCrossRef Redfors B, Sward K, Sellgren J, Ricksten SE (2009) Effects of mannitol alone and mannitol plus furosemide on renal oxygen consumption, blood flow and glomerular filtration after cardiac surgery. Intensive Care Med 35:115–122. doi:10.​1007/​s00134-008-1206-5 PubMedCrossRef
42.
go back to reference Antonelli M, Azoulay E, Bonten M et al (2010) Year in review in Intensive Care Medicine 2009: I. Pneumonia and infections, sepsis, outcome, acute renal failure and acid base, nutrition and glycaemic control. Intensive Care Med 36:196–209. doi:10.1007/s00134-009-1742-7 PubMedCrossRef Antonelli M, Azoulay E, Bonten M et al (2010) Year in review in Intensive Care Medicine 2009: I. Pneumonia and infections, sepsis, outcome, acute renal failure and acid base, nutrition and glycaemic control. Intensive Care Med 36:196–209. doi:10.​1007/​s00134-009-1742-7 PubMedCrossRef
Metadata
Title
Peri-operative interventions, but not inflammatory mediators, increase risk of acute kidney injury after cardiac surgery: a prospective cohort study
Authors
Catherine J. Morgan
Peter J. Gill
Simon Lam
Ari R. Joffe
Publication date
01-05-2013
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 5/2013
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-013-2849-4

Other articles of this Issue 5/2013

Intensive Care Medicine 5/2013 Go to the issue