Quantification of urinary TIMP-2 and IGFBP-7: an adequate diagnostic test to predict acute kidney injury after cardiac surgery?

Anna J Wetz, Eva M Richardt, Saskia Wand, Nils Kunze, Hanna Schotola, Michael Quintel, Anselm Bräuer, Onnen Moerer, Anna J Wetz, Eva M Richardt, Saskia Wand, Nils Kunze, Hanna Schotola, Michael Quintel, Anselm Bräuer, Onnen Moerer

Abstract

Introduction: Postoperative acute kidney injury (AKI) is a frequently observed complication after on-pump cardiac surgery (CS) and is associated with adverse patient outcomes. Early identification of patients at risk is essential for the prevention of AKI after CS. In this study, we analysed whether urinary tissue inhibitor of metalloproteinase 2 (TIMP-2) combined with urine insulin-like growth factor binding protein 7 (IGFBP-7) ([TIMP-2] × [IGFBP-7]) is an adequate diagnostic test to identify early AKI after on-pump CS.

Methods: In 42 patients undergoing coronary artery bypass graft surgery, we surveyed individual risk factors for AKI and defined AKI by applying the Kidney Disease: Improving Global Outcomes (KDIGO) classification during the day of surgery and the following 2 days after surgery. Concentrations of urinary TIMP-2 multiplied by IGFBP-7 were recorded at four time points: at baseline pre-surgery, at the end of surgery, 4 hours after cardiopulmonary bypass (CPB) and at 8:00 AM on the first postoperative day.

Results: In total, 38% of the patients experienced AKI. The results showed a median baseline [TIMP-2] × [IGFBP-7] concentration of 0.3 (ng/ml)(2)/1,000, decreasing at the end of surgery and then increasing at the next measurement point 4 hours after CPB and further on the first postoperative day. On the first postoperative day, patients with AKI had significantly higher concentrations of [TIMP-2] × [IGFBP-7]. On the day of surgery, the concentration did not significantly differ between patients classified as KDIGO 0 or KDIGO 1 or 2. Previously published cutoff points of 0.3 and 2 were not confirmed in our study cohort.

Conclusion: [TIMP-2] × [IGFBP-7] concentration can be used as a diagnostic test to identify patients at increased risk of AKI after CS on the first postoperative day. At earlier time points, no significant difference in [TIMP-2] × [IGFBP-7] concentration was found between patients classified as KDIGO 0 or KDIGO 1 or 2.

Trial registration: German Clinical Trials Register (DRKS) DRKS00005457. Registered 26 November 2013.

Figures

Figure 1
Figure 1
Boxplots grouped by Kidney Disease: improving global outcomes stage (0 vs. 1 or 2) and time. The measurement of urinary tissue inhibitor of metalloproteinase 2 (TIMP-2) combined with urinary insulin-like growth factor binding protein 7 (IGFBP-7) using the diagnostic test in 42 cardiac surgery patients revealed that the test was able to discriminate between patients without (dark grey) acute kidney injury (AKI) and those with (light grey) AKI on the first postoperative day (area under the receiver operating characteristic curve, 0.706). The x-axis is measurement time points 1 through 4. The y-axis is the combined concentration of [TIMP-2] × [IGFBP-7] (ng/ml)2/1,000.

References

    1. de Mendonça A, Vincent JL, Suter PM, Moreno R, Dearden NM, Antonelli M, et al. Acute renal failure in the ICU: risk factors and outcome evaluated by the SOFA score. Intensive Care Med. 2000;26:915–21. doi: 10.1007/s001340051281.
    1. Dasta JF, Kane-Gill SL, Durtschi AJ, Pathak DS, Kellum JA. Costs and outcomes of acute kidney injury (AKI) following cardiac surgery. Nephrol Dial Transplant. 2008;23:1970–4. doi: 10.1093/ndt/gfm908.
    1. Mangano CM, Diamondstone LS, Ramsay JG, Aggarwal A, Herskowitz A, Mangano DT. Renal dysfunction after myocardial revascularization: risk factors, adverse outcomes, and hospital resource utilization. Ann Intern Med. 1998;128:194–203. doi: 10.7326/0003-4819-128-3-199802010-00005.
    1. Haase M, Haase-Fielitz A, Bagshaw SM, Ronco C, Bellomo R. Cardiopulmonary bypass-associated acute kidney injury: a pigment nephropathy? Contrib Nephrol. 2007;156:340–53. doi: 10.1159/000102125.
    1. Bove T, Landoni G, Calabrò MG, Aletti G, Marino G, Cerchierini E, et al. Renoprotective action of fenoldopam in high-risk patients undergoing cardiac surgery: a prospective, double-blind, randomized clinical trial. Circulation. 2005;111:3230–5. doi: 10.1161/CIRCULATIONAHA.104.509141.
    1. Thakar CV, Arrigain S, Worley S, Yared JP, Paganini EP. A clinical score to predict acute renal failure after cardiac surgery. J Am Soc Nephrol. 2005;16:162–8. doi: 10.1681/ASN.2004040331.
    1. Lameire NH, Vanholder RC, Van Biesen WA. How to use biomarkers efficiently in acute kidney injury. Kidney Int. 2011;79:1047–50. doi: 10.1038/ki.2011.21.
    1. Kashani K, Al-Khafaji A, Ardiles T, Artigas A, Bagshaw SM, Bell M, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013;17:R25. doi: 10.1186/cc12503.
    1. Boonstra J, Post JA. Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells. Gene. 2004;337:1–13. doi: 10.1016/j.gene.2004.04.032.
    1. Rodier F, Campisi J, Bhaumik D. Two faces of p53: aging and tumor suppression. Nucleic Acids Res. 2007;35:7475–84. doi: 10.1093/nar/gkm744.
    1. Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol. 2006;17:1503–20. doi: 10.1681/ASN.2006010017.
    1. Yang QH, Liu DW, Long Y, Liu HZ, Chai WZ, Wang XT. Acute renal failure during sepsis: potential role of cell cycle regulation. J Infect. 2009;58:459–64. doi: 10.1016/j.jinf.2009.04.003.
    1. Meersch M, Schmidt C, Van Aken H, Martens S, Rossaint J, Singbartl K, et al. Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PLoS One. 2014;9:e93460. doi: 10.1371/journal.pone.0093460.
    1. Disease K. Improving global outcomes (KDIGO) acute kidney injury work group: KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2:1–138. doi: 10.1038/kisup.2012.1.
    1. Murray PT, Le Gall JR, Dos Reis MD, Pinsky MR, Tetta C. Physiologic endpoints (efficacy) for acute renal failure studies. Curr Opin Crit Care. 2002;8:519–25. doi: 10.1097/00075198-200212000-00007.
    1. Bellomo R, Kellum JA, Ronco C. Defining acute renal failure: physiological principles. Intensive Care Med. 2004;30:33–7. doi: 10.1007/s00134-003-2078-3.
    1. Solomon R, Segal A. Defining acute kidney injury: what is the most appropriate metric? Nat Clin Pract Nephrol. 2008;4:208–15. doi: 10.1038/ncpneph0746.
    1. Aregger F, Uehlinger DE, Witowski J, Brunisholz RA, Hunziker P, Frey FJ, et al. Identification of IGFBP-7 by urinary proteomics as a novel prognostic marker in early acute kidney injury. Kidney Int. 2014;85:909–19. doi: 10.1038/ki.2013.363.
    1. McCullough PA, Bouchard J, Waikar SS, Siew ED, Endre ZH, Goldstein SL, et al. Implementation of novel biomarkers in the diagnosis, prognosis, and management of acute kidney injury: executive summary from the Tenth Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Contrib Nephrol. 2013;182:5–12. doi: 10.1159/000349962.
    1. Murray PT, Mehta RL, Shaw A, Ronco C, Endre Z, Kellum JA, et al. Potential use of biomarkers in acute kidney injury: report and summary of recommendations from the 10th Acute Dialysis Quality Initiative consensus conference. Kidney Int. 2014;85:513–21. doi: 10.1038/ki.2013.374.
    1. Haase M, Kellum JA, Ronco C. Subclinical AKI—an emerging syndrome with important consequences. Nat Rev Nephrol. 2012;8:735–9. doi: 10.1038/nrneph.2012.197.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit