Skip to main content
Top
Published in: BMC Nephrology 1/2021

Open Access 01-12-2021 | Heart Surgery | Research

Blood and urinary cytokine balance and renal outcomes at cardiac surgery

Authors: William T. McBride, Mary Jo Kurth, Anna Domanska, Joanne Watt, Gavin McLean, Jijin Joseph, John V. Lamont, Peter Fitzgerald, Mark W. Ruddock

Published in: BMC Nephrology | Issue 1/2021

Login to get access

Abstract

Background

Increased perioperative pro-inflammatory biomarkers, renal hypoperfusion and ischemia reperfusion injury (IRI) heighten cardiac surgery acute kidney injury (CS-AKI) risk. Increased urinary anti-inflammatory cytokines attenuate risk. We evaluated whether blood and urinary anti-inflammatory biomarkers, when expressed as ratios with biomarkers of inflammation, hypoperfusion and IRI are increased in CS-AKI patients.

Methods

Preoperative and 24-h postoperative blood and urinary pro-inflammatory and anti-inflammatory cytokines, blood VEGF and H-FABP (hypoperfusion biomarkers), and MK, a biomarker for IRI, were measured in 401 cardiac surgery patients. Pre- and postoperative concentrations of biomarkers and selected ratios thereof, were compared between non-CS-AKI and CS-AKI patients.

Results

Compared with non-CS-AKI, blood pro-inflammatory (pre- and post-op TNFα, IP-10, IL-12p40, MIP-1α, NGAL; pre-op IL-6; post-op IL-8, MK) and anti-inflammatory (pre- and post-op sTNFsr1, sTNFsr2, IL-1RA) biomarkers together with urinary pro-inflammatory (pre- and post-op uIL-12p40; post-op uIP-10, uNGAL) and anti-inflammatory (pre- and post-op usTNFsr1, usTNFsr2, uIL-1RA) biomarkers, were significantly higher in CS-AKI patients. Urinary anti-inflammatory biomarkers, when expressed as ratios with biomarkers of inflammation (blood and urine), hypoperfusion (blood H-FABP and VEGF) and IRI (blood MK) were decreased in CS-AKI. In contrast, blood anti-inflammatory biomarkers expressed as similar ratios with blood biomarkers were increased in CS-AKI.

Conclusions

The urinary anti-inflammatory response may protect against the injurious effects of perioperative inflammation, hypoperfusion and IRI. These finding may have clinical utility in bioprediction and earlier diagnosis of CS-AKI and informing future therapeutic strategies for CS-AKI patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ho J, Tangri N, Komenda P, Kaushal A, Sood M, Brar R, et al. Urinary, plasma, and serum biomarkers’ utility for predicting acute kidney injury associated with cardiac surgery in adults: a meta-analysis. Am J Kidney Dis WB Saunders. 2015;66:993–1005.CrossRef Ho J, Tangri N, Komenda P, Kaushal A, Sood M, Brar R, et al. Urinary, plasma, and serum biomarkers’ utility for predicting acute kidney injury associated with cardiac surgery in adults: a meta-analysis. Am J Kidney Dis WB Saunders. 2015;66:993–1005.CrossRef
2.
go back to reference Bucholz EM, Whitlock RP, Zappitelli M, Devarajan P, Eikelboom J, Garg AX, et al. Cardiac biomarkers and acute kidney injury after cardiac surgery. Pediatr Am Acad Pediatr. 2015;135:e945–56. Bucholz EM, Whitlock RP, Zappitelli M, Devarajan P, Eikelboom J, Garg AX, et al. Cardiac biomarkers and acute kidney injury after cardiac surgery. Pediatr Am Acad Pediatr. 2015;135:e945–56.
3.
go back to reference Vaidya VS, Waikar SS, Ferguson MA, Collings FB, Sunderland K, Gioules C, et al. Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clin Transl Sci. 2008;1:200–8.CrossRef Vaidya VS, Waikar SS, Ferguson MA, Collings FB, Sunderland K, Gioules C, et al. Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clin Transl Sci. 2008;1:200–8.CrossRef
4.
go back to reference Sato W, Kadomatsu K, Yuzawa Y, Muramatsu H, Hotta N, Matsuo S, et al. Midkine is involved in neutrophil infiltration into the tubulointerstitium in ischemic renal injury. J Immunol. 2001;167:3463–9.CrossRef Sato W, Kadomatsu K, Yuzawa Y, Muramatsu H, Hotta N, Matsuo S, et al. Midkine is involved in neutrophil infiltration into the tubulointerstitium in ischemic renal injury. J Immunol. 2001;167:3463–9.CrossRef
5.
go back to reference Kinsey GR, Li L, Okusa MD. Inflammation in acute kidney injury. Nephron Exp Nephrol. 2008;109:e102–7.CrossRef Kinsey GR, Li L, Okusa MD. Inflammation in acute kidney injury. Nephron Exp Nephrol. 2008;109:e102–7.CrossRef
6.
go back to reference Lien YHH, Lai LW, Silva AL. Pathogenesis of renal ischemia/reperfusion injury: Lessons from knockout mice. Life Sci. 2003:543–52. Lien YHH, Lai LW, Silva AL. Pathogenesis of renal ischemia/reperfusion injury: Lessons from knockout mice. Life Sci. 2003:543–52.
7.
go back to reference McBride WT, Prasad PS, Armstrong M, Patterson C, Gilliland H, Drain A, et al. Cytokine phenotype, genotype, and renal outcomes at cardiac surgery. Cytokine. 2013;61:275–84.CrossRef McBride WT, Prasad PS, Armstrong M, Patterson C, Gilliland H, Drain A, et al. Cytokine phenotype, genotype, and renal outcomes at cardiac surgery. Cytokine. 2013;61:275–84.CrossRef
8.
go back to reference McBride WT, Armstrong MA, Crockard AD, McMurray TJ, Rea JM. Cytokine balance and immunosuppressive changes at cardiac surgery: contrasting response between patients and isolated CPB circuits. Br J Anaesth. 1995;75:724–33.CrossRef McBride WT, Armstrong MA, Crockard AD, McMurray TJ, Rea JM. Cytokine balance and immunosuppressive changes at cardiac surgery: contrasting response between patients and isolated CPB circuits. Br J Anaesth. 1995;75:724–33.CrossRef
9.
go back to reference McBride WT, Kurth MJ, McLean G, Domanska A, Lamont JV, Maguire D, et al. Stratifying risk of acute kidney injury in pre and post cardiac surgery patients using a novel biomarker-based algorithm and clinical risk score. Sci reports 2019 91. Nat Publ Group. 2019;9:1–12. McBride WT, Kurth MJ, McLean G, Domanska A, Lamont JV, Maguire D, et al. Stratifying risk of acute kidney injury in pre and post cardiac surgery patients using a novel biomarker-based algorithm and clinical risk score. Sci reports 2019 91. Nat Publ Group. 2019;9:1–12.
10.
go back to reference Gormley SMC, McBride WT, Armstrong MA, Young IS, McClean E, MacGowan SW, et al. Plasma and urinary cytokine homeostasis and renal dysfunction during cardiac surgery. Anesthesiology. 2000;93:1210–6.CrossRef Gormley SMC, McBride WT, Armstrong MA, Young IS, McClean E, MacGowan SW, et al. Plasma and urinary cytokine homeostasis and renal dysfunction during cardiac surgery. Anesthesiology. 2000;93:1210–6.CrossRef
11.
go back to reference McBride WT, Allen S, Gormley SMC, Young IS, McClean E, MacGowan SW, et al. Methylprednisolone favourably alters plasma and urinary cytokine homeostasis and subclinical renal injury at cardiac surgery. Cytokine. 2004;27:81–9.CrossRef McBride WT, Allen S, Gormley SMC, Young IS, McClean E, MacGowan SW, et al. Methylprednisolone favourably alters plasma and urinary cytokine homeostasis and subclinical renal injury at cardiac surgery. Cytokine. 2004;27:81–9.CrossRef
12.
go back to reference Allen SJ, McBride WT, McMurray TJ, Phillips AS, Penugonda SP, Campalani G, et al. Cell salvage alters the systemic inflammatory response after off-pump coronary artery bypass grafting surgery. Ann Thorac Surg. 2007;83:578–85.CrossRef Allen SJ, McBride WT, McMurray TJ, Phillips AS, Penugonda SP, Campalani G, et al. Cell salvage alters the systemic inflammatory response after off-pump coronary artery bypass grafting surgery. Ann Thorac Surg. 2007;83:578–85.CrossRef
13.
go back to reference Baker RC, Armstrong MA, Allen SJ, McBride WT. Role of the kidney in perioperative inflammatory responses. Br J Anaesth. 2002;88:330–4.CrossRef Baker RC, Armstrong MA, Allen SJ, McBride WT. Role of the kidney in perioperative inflammatory responses. Br J Anaesth. 2002;88:330–4.CrossRef
14.
go back to reference Chatterjee PK, Hawksworth GM, McLay JS. Cytokine-stimulated nitric oxide production in the human renal proximal tubule and its modulation by natriuretic peptides: a novel immunomodulatory mechanism? Exp Nephrol. 1999;7:438–48.CrossRef Chatterjee PK, Hawksworth GM, McLay JS. Cytokine-stimulated nitric oxide production in the human renal proximal tubule and its modulation by natriuretic peptides: a novel immunomodulatory mechanism? Exp Nephrol. 1999;7:438–48.CrossRef
15.
go back to reference Wolkow PP, Niewczas MA, Perkins B, Ficociello LH, Lipinski B, Warram JH, et al. Association of urinary inflammatory markers and renal decline in microalbuminuric type 1 diabetics. J am Soc Nephrol. American society of. Nephrology. 2008;19:789–97. Wolkow PP, Niewczas MA, Perkins B, Ficociello LH, Lipinski B, Warram JH, et al. Association of urinary inflammatory markers and renal decline in microalbuminuric type 1 diabetics. J am Soc Nephrol. American society of. Nephrology. 2008;19:789–97.
16.
go back to reference Bocci V, Pacini A, Pessina GP, Maioli E, Naldini A. Studies on tumor necrosis factor (TNF)-I. pharmacokinetics of human recombinant TNF in rabbits and monkeys after intravenous administration. Gen Pharmacol Pergamon. 1987;18:343–6.CrossRef Bocci V, Pacini A, Pessina GP, Maioli E, Naldini A. Studies on tumor necrosis factor (TNF)-I. pharmacokinetics of human recombinant TNF in rabbits and monkeys after intravenous administration. Gen Pharmacol Pergamon. 1987;18:343–6.CrossRef
17.
go back to reference Arthur JM, Hill EG, Alge JL, Lewis EC, Neely BA, Janech MG, et al. Evaluation of 32 urine biomarkers to predict the progression of acute kidney injury after cardiac surgery. Kidney Int. 2014;85:431–8.CrossRef Arthur JM, Hill EG, Alge JL, Lewis EC, Neely BA, Janech MG, et al. Evaluation of 32 urine biomarkers to predict the progression of acute kidney injury after cardiac surgery. Kidney Int. 2014;85:431–8.CrossRef
18.
go back to reference Kirby NA, Stepanek AM, Vernet A, Schmidt SM, Schultz CL, Parry NM, et al. Urinary MCP1 and Microalbumin increase prior to onset of Azotemia in mice with polycystic kidney disease. Comp Med. 2014;64:99–105.PubMedPubMedCentral Kirby NA, Stepanek AM, Vernet A, Schmidt SM, Schultz CL, Parry NM, et al. Urinary MCP1 and Microalbumin increase prior to onset of Azotemia in mice with polycystic kidney disease. Comp Med. 2014;64:99–105.PubMedPubMedCentral
19.
go back to reference De Melo EN, Deda L, Har R, Reich HN, Scholey JW, Daneman D, et al. The urinary inflammatory profile in gluten free diet - Adherent adolescents with type 1 diabetes and celiac disease. J Diabetes Complications. 2016;30:295–9.CrossRef De Melo EN, Deda L, Har R, Reich HN, Scholey JW, Daneman D, et al. The urinary inflammatory profile in gluten free diet - Adherent adolescents with type 1 diabetes and celiac disease. J Diabetes Complications. 2016;30:295–9.CrossRef
20.
go back to reference Malek M, Nematbakhsh M. Renal ischemia/reperfusion injury; from pathophysiology to treatment. J Ren Inj Prev. 2015;4:20–207.PubMedPubMedCentral Malek M, Nematbakhsh M. Renal ischemia/reperfusion injury; from pathophysiology to treatment. J Ren Inj Prev. 2015;4:20–207.PubMedPubMedCentral
21.
go back to reference Peng H, Mao Y, Fu X, Feng Z, Xu J. Comparison of biomarkers in rat renal ischemia-reperfusion injury. Int J Clin Exp Med. 2015;8:7577–84.PubMedPubMedCentral Peng H, Mao Y, Fu X, Feng Z, Xu J. Comparison of biomarkers in rat renal ischemia-reperfusion injury. Int J Clin Exp Med. 2015;8:7577–84.PubMedPubMedCentral
22.
go back to reference Hoste EAJ, Kellum JA, Katz NM, Rosner MH, Haase M, Ronco C. Epidemiology of acute kidney injury. Cardiorenal Syndr Crit Care. 2010:1–8. Hoste EAJ, Kellum JA, Katz NM, Rosner MH, Haase M, Ronco C. Epidemiology of acute kidney injury. Cardiorenal Syndr Crit Care. 2010:1–8.
23.
go back to reference Bagshaw SM, Uchino S, Cruz D, Bellomo R, Morimatsu H, Morgera S, et al. A comparison of observed versus estimated baseline creatinine for determination of RIFLE class in patients with acute kidney injury. Nephrol Dial Transpl. 2009;24:2739–44.CrossRef Bagshaw SM, Uchino S, Cruz D, Bellomo R, Morimatsu H, Morgera S, et al. A comparison of observed versus estimated baseline creatinine for determination of RIFLE class in patients with acute kidney injury. Nephrol Dial Transpl. 2009;24:2739–44.CrossRef
24.
go back to reference Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999;130:461–70.CrossRef Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999;130:461–70.CrossRef
25.
go back to reference Chirumamilla AP, Wilson MF, Wilding GE, Chandrasekhar R, Ashraf H. Outcome of renal insufficiency patients undergoing coronary artery bypass graft surgery. Cardiology. 2008;111:23–9.CrossRef Chirumamilla AP, Wilson MF, Wilding GE, Chandrasekhar R, Ashraf H. Outcome of renal insufficiency patients undergoing coronary artery bypass graft surgery. Cardiology. 2008;111:23–9.CrossRef
Metadata
Title
Blood and urinary cytokine balance and renal outcomes at cardiac surgery
Authors
William T. McBride
Mary Jo Kurth
Anna Domanska
Joanne Watt
Gavin McLean
Jijin Joseph
John V. Lamont
Peter Fitzgerald
Mark W. Ruddock
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2021
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-021-02621-6

Other articles of this Issue 1/2021

BMC Nephrology 1/2021 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.