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Published in: Annals of Intensive Care 1/2015

Open Access 01-12-2015 | Research

Urinary [TIMP-2]*[IGFBP7] for early prediction of acute kidney injury after coronary artery bypass surgery

Authors: Kevin Pilarczyk, Michaela Edayadiyil-Dudasova, Daniel Wendt, Ender Demircioglu, Jaroslav Benedik, Daniel Sebastian Dohle, Heinz Jakob, Fabian Dusse

Published in: Annals of Intensive Care | Issue 1/2015

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Abstract

Background

Acute kidney injury (AKI) is a common complication after cardiac surgery. Currently, prediction of AKI with classical tools remains uncertain. Therefore, it was the aim of the present study to evaluate two new urinary biomarkers—insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in patients after coronary artery bypass surgery (CABG).

Methods

In a prospective cohort study, 60 consecutive patients undergoing isolated on-pump CABG were enrolled. Urine samples collected every 12 h in the postoperative course were analyzed for the product of TIMP-2 and IGFBP7. Urinary output, serum creatinine and estimated glomerular filtration rate (eGFR) were recorded simultaneously. Primary clinical endpoint was the development of AKI stage 2 or 3 according to the classification of the KDIGO within 48 h after surgery.

Results

48 male and 12 female patients with a mean age of 69.61 ± 8.4 years were included. 19 patients developed an AKI (31.6 %), six patients met the endpoint with AKI 2 or 3 (10 %). Urinary [TIMP-2]*[IGFBP7] increased significantly as early as 4 h after CABG in patients with AKI 2/3 (1.83 ± 2.15 vs. 0.23 ± 0.45, p < 0.05) whereas serum creatinine did not increase until 48 h after surgery. The diagnostic accuracy of [TIMP 2]*[IGFBP7] on day one after surgery for the prediction of AKI 2/3 was significantly better (sensitivity 0.89, specificity 0.81, AUC 0.817, 95 % CI 0.622–1.0 SE 0.099, p = 0.022, cut-off 0.817) than for serum creatinine (AUC 0.359, sensitivity 0.50, specificity of 0.52, cut-off value 1.17 mg/dl) and eGFR.

Conclusion

Urinary [TIMP-2]*[IGFBP7] represents a sensitive and specific biomarker to predict moderate to severe AKI very early after CABG. Analyses from our ongoing larger study are necessary to confirm these findings and probably increase sensitivity and specificity.
Literature
1.
go back to reference Rosner MH, Okusa MD. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol. 2006;1(1):19–32.CrossRefPubMed Rosner MH, Okusa MD. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol. 2006;1(1):19–32.CrossRefPubMed
2.
go back to reference Machado MN, Nakazone MA, Maia LN. Prognostic value of acute kidney injury after cardiac surgery according to kidney disease: improving global outcomes definition and staging (KDIGO) criteria. PLoS One. 2014;9(5):e98028.PubMedCentralCrossRefPubMed Machado MN, Nakazone MA, Maia LN. Prognostic value of acute kidney injury after cardiac surgery according to kidney disease: improving global outcomes definition and staging (KDIGO) criteria. PLoS One. 2014;9(5):e98028.PubMedCentralCrossRefPubMed
3.
go back to reference Schiffl H, Fischer R. Five-year outcomes of severe acute kidney injury requiring renal replacement therapy. Nephrol Dial Transplant. 2008;23(7):2235–41.CrossRefPubMed Schiffl H, Fischer R. Five-year outcomes of severe acute kidney injury requiring renal replacement therapy. Nephrol Dial Transplant. 2008;23(7):2235–41.CrossRefPubMed
4.
go back to reference Schmitt R, Coca S, Kanbay M, Tinetti ME, Cantley LG, Parikh CR. Recovery of kidney function after acute kidney injury in the elderly: a systematic review and meta-analysis. Am J Kidney Dis. 2008;52(2):262–71.CrossRefPubMed Schmitt R, Coca S, Kanbay M, Tinetti ME, Cantley LG, Parikh CR. Recovery of kidney function after acute kidney injury in the elderly: a systematic review and meta-analysis. Am J Kidney Dis. 2008;52(2):262–71.CrossRefPubMed
5.
go back to reference Karkouti K, Wijeysundera DN, Yau TM, Callum JL, Cheng DC, Crowther M, Dupuis JY, Fremes SE, Kent B, Laflamme C, Lamy A, Legare JF, Mazer CD, McCluskey SA, Rubens FD, Sawchuk C, Beattie WS. Acute kidney injury after cardiac surgery: focus on modifiable risk factors. Circulation. 2009;119(4):495–502.CrossRefPubMed Karkouti K, Wijeysundera DN, Yau TM, Callum JL, Cheng DC, Crowther M, Dupuis JY, Fremes SE, Kent B, Laflamme C, Lamy A, Legare JF, Mazer CD, McCluskey SA, Rubens FD, Sawchuk C, Beattie WS. Acute kidney injury after cardiac surgery: focus on modifiable risk factors. Circulation. 2009;119(4):495–502.CrossRefPubMed
6.
go back to reference Karvellas CJ, Farhat MR, Sajjad I, Mogensen SS, Leung AA, Wald R, Bagshaw SM. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis. Crit Care. 2011;15(1):R72.PubMedCentralCrossRefPubMed Karvellas CJ, Farhat MR, Sajjad I, Mogensen SS, Leung AA, Wald R, Bagshaw SM. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis. Crit Care. 2011;15(1):R72.PubMedCentralCrossRefPubMed
7.
go back to reference Brienza N, Giglio MT, Marucci M, Fiore T. Does perioperative hemodynamic optimization protect renal function in surgical patients? A meta-analytic study. Crit Care Med. 2009;37(6):2079–90.CrossRefPubMed Brienza N, Giglio MT, Marucci M, Fiore T. Does perioperative hemodynamic optimization protect renal function in surgical patients? A meta-analytic study. Crit Care Med. 2009;37(6):2079–90.CrossRefPubMed
8.
go back to reference Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol. 2006;17(6):1503–20.CrossRefPubMed Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol. 2006;17(6):1503–20.CrossRefPubMed
9.
go back to reference Kashani K, Al-Khafaji A, Ardiles T, Artigas A, Bagshaw SM, Bell M, Bihorac A, Birkhahn R, Cely CM, Chawla LS, Davison DL, Feldkamp T, Forni LG, Gong MN, Gunnerson KJ, Haase M, Hackett J, Honore PM, Hoste EA, Joannes-Boyau O, Joannidis M, Kim P, Koyner JL, Laskowitz DT, Lissauer ME, Marx G, McCullough PA, Mullaney S, Ostermann M, Rimmelé T, Shapiro NI, Shaw AD, Shi J, Sprague AM, Vincent JL, Vinsonneau C, Wagner L, Walker MG, Wilkerson RG, Zacharowski K, Kellum JA. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013;17(1):R25.PubMedCentralCrossRefPubMed Kashani K, Al-Khafaji A, Ardiles T, Artigas A, Bagshaw SM, Bell M, Bihorac A, Birkhahn R, Cely CM, Chawla LS, Davison DL, Feldkamp T, Forni LG, Gong MN, Gunnerson KJ, Haase M, Hackett J, Honore PM, Hoste EA, Joannes-Boyau O, Joannidis M, Kim P, Koyner JL, Laskowitz DT, Lissauer ME, Marx G, McCullough PA, Mullaney S, Ostermann M, Rimmelé T, Shapiro NI, Shaw AD, Shi J, Sprague AM, Vincent JL, Vinsonneau C, Wagner L, Walker MG, Wilkerson RG, Zacharowski K, Kellum JA. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013;17(1):R25.PubMedCentralCrossRefPubMed
10.
go back to reference Bihorac A, Chawla LS, Shaw AD, Al-Khafaji A, Davison DL, Demuth GE, Fitzgerald R, Gong MN, Graham DD, Gunnerson K, Heung M, Jortani S, Kleerup E, Koyner JL, Krell K, Letourneau J, Lissauer M, Miner J, Nguyen HB, Ortega LM, Self WH, Sellman R, Shi J, Straseski J, Szalados JE, Wilber ST, Walker MG, Wilson J, Wunderink R, Zimmerman J, Kellum JA. Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication. Am J Respir Crit Care Med. 2014;189(8):932–9.CrossRefPubMed Bihorac A, Chawla LS, Shaw AD, Al-Khafaji A, Davison DL, Demuth GE, Fitzgerald R, Gong MN, Graham DD, Gunnerson K, Heung M, Jortani S, Kleerup E, Koyner JL, Krell K, Letourneau J, Lissauer M, Miner J, Nguyen HB, Ortega LM, Self WH, Sellman R, Shi J, Straseski J, Szalados JE, Wilber ST, Walker MG, Wilson J, Wunderink R, Zimmerman J, Kellum JA. Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication. Am J Respir Crit Care Med. 2014;189(8):932–9.CrossRefPubMed
11.
go back to reference Meersch M, Schmidt C, Van Aken H, Martens S, Rossaint J, Singbartl K, Görlich D, Kellum JA, Zarbock A. Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PLoS One. 2014;9(3):e93460.PubMedCentralCrossRefPubMed Meersch M, Schmidt C, Van Aken H, Martens S, Rossaint J, Singbartl K, Görlich D, Kellum JA, Zarbock A. Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PLoS One. 2014;9(3):e93460.PubMedCentralCrossRefPubMed
12.
go back to reference Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Moher D, Rennie D, de Vet HC, Lijmer JG. Standards for Reporting of Diagnostic Accuracy. The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Clin Chem. 2003;49(1):7–18.CrossRefPubMed Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Moher D, Rennie D, de Vet HC, Lijmer JG. Standards for Reporting of Diagnostic Accuracy. The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Clin Chem. 2003;49(1):7–18.CrossRefPubMed
13.
go back to reference Thielmann M, Kottenberg E, Kleinbongard P, Wendt D, Gedik N, Pasa S, Price V, Tsagakis K, Neuhäuser M, Peters J, Jakob H, Heusch G. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet. 2013;382(9892):597–604.CrossRefPubMed Thielmann M, Kottenberg E, Kleinbongard P, Wendt D, Gedik N, Pasa S, Price V, Tsagakis K, Neuhäuser M, Peters J, Jakob H, Heusch G. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet. 2013;382(9892):597–604.CrossRefPubMed
14.
go back to reference Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int 2012. Suppl, 2: 1–138. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int 2012. Suppl, 2: 1–138.
15.
go back to reference Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R. Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.CrossRefPubMed Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R. Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.CrossRefPubMed
16.
go back to reference Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C. Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294(7):813–8.CrossRefPubMed Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C. Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294(7):813–8.CrossRefPubMed
17.
go back to reference Waikar SS, Betensky RA, Emerson SC, Bonventre JV. Imperfect gold standards for kidney injury biomarker evaluation. J Am Soc Nephrol. 2012;23(1):13–21.PubMedCentralCrossRefPubMed Waikar SS, Betensky RA, Emerson SC, Bonventre JV. Imperfect gold standards for kidney injury biomarker evaluation. J Am Soc Nephrol. 2012;23(1):13–21.PubMedCentralCrossRefPubMed
18.
go back to reference Svenmarker S, Häggmark S, Holmgren A, Näslund U. Serum markers are not reliable measures of renal function in conjunction with cardiopulmonary bypass. Interact CardioVasc Thorac Surg. 2011;12(5):713–7.CrossRefPubMed Svenmarker S, Häggmark S, Holmgren A, Näslund U. Serum markers are not reliable measures of renal function in conjunction with cardiopulmonary bypass. Interact CardioVasc Thorac Surg. 2011;12(5):713–7.CrossRefPubMed
19.
go back to reference Ronco C, Bellomo R. Prevention of acute renal failure in the critically ill. Nephron Clin Pract. 2003;93(1):C13–20.CrossRefPubMed Ronco C, Bellomo R. Prevention of acute renal failure in the critically ill. Nephron Clin Pract. 2003;93(1):C13–20.CrossRefPubMed
20.
go back to reference Zhang Z, Xu X, Ni H, Jin N. Serum cystatin C is associated with renal function recovery in critically ill patients undergoing continuous renal replacement therapy. Nephron Clin Pract. 2012;122(3–4):86–92.CrossRefPubMed Zhang Z, Xu X, Ni H, Jin N. Serum cystatin C is associated with renal function recovery in critically ill patients undergoing continuous renal replacement therapy. Nephron Clin Pract. 2012;122(3–4):86–92.CrossRefPubMed
21.
go back to reference Nejat M, Pickering JW, Walker RJ, Westhuyzen J, Shaw GM, Frampton CM, Endre ZH. Urinary cystatin C is diagnostic of acute kidney injury and sepsis, and predicts mortality in the intensive care unit. Crit Care. 2010;14(3):R85.PubMedCentralCrossRefPubMed Nejat M, Pickering JW, Walker RJ, Westhuyzen J, Shaw GM, Frampton CM, Endre ZH. Urinary cystatin C is diagnostic of acute kidney injury and sepsis, and predicts mortality in the intensive care unit. Crit Care. 2010;14(3):R85.PubMedCentralCrossRefPubMed
22.
go back to reference Perry TE, Muehlschlegel JD, Liu KY, Fox AA, Collard CD, Shernan SK, Body SC. CABG Genomics Investigators. Plasma neutrophil gelatinase-associated lipocalin and acute postoperative kidney injury in adult cardiac surgical patients. Anesth Analg. 2010;110(6):1541–7.PubMedCentralCrossRefPubMed Perry TE, Muehlschlegel JD, Liu KY, Fox AA, Collard CD, Shernan SK, Body SC. CABG Genomics Investigators. Plasma neutrophil gelatinase-associated lipocalin and acute postoperative kidney injury in adult cardiac surgical patients. Anesth Analg. 2010;110(6):1541–7.PubMedCentralCrossRefPubMed
23.
go back to reference Hoste EA, McCullough PA, Kashani K, Chawla LS, Joannidis M, Shaw AD, Feldkamp T, Uettwiller-Geiger DL, McCarthy P, Shi J, Walker MG, Kellum JA, Sapphire Investigators. Derivation and validation of cutoffs for clinical use of cell cycle arrest biomarkers. Nephrol Dial Transplant. 2014;29(11):2054–61.PubMedCentralCrossRefPubMed Hoste EA, McCullough PA, Kashani K, Chawla LS, Joannidis M, Shaw AD, Feldkamp T, Uettwiller-Geiger DL, McCarthy P, Shi J, Walker MG, Kellum JA, Sapphire Investigators. Derivation and validation of cutoffs for clinical use of cell cycle arrest biomarkers. Nephrol Dial Transplant. 2014;29(11):2054–61.PubMedCentralCrossRefPubMed
24.
go back to reference Meersch M, Schmidt C, Van Aken H, Rossaint J, Görlich D, Stege D, Malec E, Januszewska K, Zarbock A. Validation of cell-cycle arrest biomarkers for acute kidney injury after pediatric cardiac surgery. PLoS One. 2014;9(10):e110865.PubMedCentralCrossRefPubMed Meersch M, Schmidt C, Van Aken H, Rossaint J, Görlich D, Stege D, Malec E, Januszewska K, Zarbock A. Validation of cell-cycle arrest biomarkers for acute kidney injury after pediatric cardiac surgery. PLoS One. 2014;9(10):e110865.PubMedCentralCrossRefPubMed
25.
go back to reference Ponce D, Zorzenon Cde P, dos Santos NY, Balbi AL. Early nephrology consultation can have an impact on outcome of acute kidney injury patients. Nephrol Dial Transplant. 2011;26(10):3202–6.CrossRefPubMed Ponce D, Zorzenon Cde P, dos Santos NY, Balbi AL. Early nephrology consultation can have an impact on outcome of acute kidney injury patients. Nephrol Dial Transplant. 2011;26(10):3202–6.CrossRefPubMed
26.
go back to reference Liu Y, Davari-Farid S, Arora P, Porhomayon J, Nader ND. Early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury after cardiac surgery: a systematic review and meta-analysis. J Cardiothorac Vasc Anesth. 2014;28(3):557–63.CrossRefPubMed Liu Y, Davari-Farid S, Arora P, Porhomayon J, Nader ND. Early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury after cardiac surgery: a systematic review and meta-analysis. J Cardiothorac Vasc Anesth. 2014;28(3):557–63.CrossRefPubMed
27.
go back to reference Zarbock A, Schmidt C, Van Aken H, Wempe C, Martens S, Zahn PK, Wolf B, Goebel U, Schwer CI, Rosenberger P, Haeberle H, Görlich D, Kellum JA, Meersch M, RenalRIPC Investigators. Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. JAMA. 2015;313(21):2133–41.CrossRefPubMed Zarbock A, Schmidt C, Van Aken H, Wempe C, Martens S, Zahn PK, Wolf B, Goebel U, Schwer CI, Rosenberger P, Haeberle H, Görlich D, Kellum JA, Meersch M, RenalRIPC Investigators. Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. JAMA. 2015;313(21):2133–41.CrossRefPubMed
Metadata
Title
Urinary [TIMP-2]*[IGFBP7] for early prediction of acute kidney injury after coronary artery bypass surgery
Authors
Kevin Pilarczyk
Michaela Edayadiyil-Dudasova
Daniel Wendt
Ender Demircioglu
Jaroslav Benedik
Daniel Sebastian Dohle
Heinz Jakob
Fabian Dusse
Publication date
01-12-2015
Publisher
Springer Paris
Published in
Annals of Intensive Care / Issue 1/2015
Electronic ISSN: 2110-5820
DOI
https://doi.org/10.1186/s13613-015-0076-6

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