Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial

Melanie Meersch, Christoph Schmidt, Andreas Hoffmeier, Hugo Van Aken, Carola Wempe, Joachim Gerss, Alexander Zarbock, Melanie Meersch, Christoph Schmidt, Andreas Hoffmeier, Hugo Van Aken, Carola Wempe, Joachim Gerss, Alexander Zarbock

Abstract

Purpose: Care bundles are recommended in patients at high risk for acute kidney injury (AKI), although they have not been proven to improve outcomes. We sought to establish the efficacy of an implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines to prevent cardiac surgery-associated AKI in high risk patients defined by renal biomarkers.

Methods: In this single-center trial, we examined the effect of a "KDIGO bundle" consisting of optimization of volume status and hemodynamics, avoidance of nephrotoxic drugs, and preventing hyperglycemia in high risk patients defined as urinary [TIMP-2]·[IGFBP7] > 0.3 undergoing cardiac surgery. The primary endpoint was the rate of AKI defined by KDIGO criteria within the first 72 h after surgery. Secondary endpoints included AKI severity, need for dialysis, length of stay, and major adverse kidney events (MAKE) at days 30, 60, and 90.

Results: AKI was significantly reduced with the intervention compared to controls [55.1 vs. 71.7%; ARR 16.6% (95 CI 5.5-27.9%); p = 0.004]. The implementation of the bundle resulted in significantly improved hemodynamic parameters at different time points (p < 0.05), less hyperglycemia (p < 0.001) and use of ACEi/ARBs (p < 0.001) compared to controls. Rates of moderate to severe AKI were also significantly reduced by the intervention compared to controls. There were no significant effects on other secondary outcomes.

Conclusion: An implementation of the KDIGO guidelines compared with standard care reduced the frequency and severity of AKI after cardiac surgery in high risk patients. Adequately powered multicenter trials are warranted to examine mortality and long-term renal outcomes.

Keywords: Acute kidney injury; Biomarkers; Cardiac surgery; KDIGO guidelines; Major adverse kidney events; [TIMP-2]·[IGFBP7].

Conflict of interest statement

Conflicts of interest

AZ has received unrestricted grant and lecture fees from Astute Medical as well as lecture fees from Fresenius and Braun. MM has received lecture fees from Astute Medical. The remaining authors declare that they have no conflicts of interest.

Funding/support

The trial is registered at http://apps.who.int/trialsearch/ (Identifier: DRKS00006139). The study was supported by the German Research Foundation (428/6-1 to AZ), the European Society of Intensive Care Medicine, the Innovative Medizinische Forschung (to MM), and an unrestricted research grant from Astute Medical.

Figures

Fig. 1
Fig. 1
Trial flowchart. Enrolled patients are randomized to study groups
Fig. 2
Fig. 2
Occurrence of cardiac surgery-associated AKI. Rate of CSA-AKI in control and intervention groups

References

    1. Hobson CE, Yavas S, Segal MS, Schold JD, Tribble CG, Layon AJ, Bihorac A. Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation. 2009;119:2444–2453. doi: 10.1161/CIRCULATIONAHA.108.800011.
    1. Landoni G, Bove T, Szekely A, Comis M, Rodseth RN, Pasero D, Ponschab M, Mucchetti M, Bove T, Azzolini ML, Caramelli F, Paternoster G, Pala G, Cabrini L, Amitrano D, Borghi G, Capasso A, Cariello C, Carpanese A, Feltracco P, Gottin L, Lobreglio R, Mattioli L, Monaco F, Morgese F, Musu M, Pasin L, Pisano A, Roasio A, Russo G, Slaviero G, Villari N, Vittorio A, Zucchetti M, Guarracino F, Morelli A, De Santis V, Del Sarto PA, Corcione A, Ranieri M, Finco G, Zangrillo A, Bellomo R. Reducing mortality in acute kidney injury patients: systematic review and international web-based survey. J Cardiothorac Vasc Anesth. 2013;27:1384–1398. doi: 10.1053/j.jvca.2013.06.028.
    1. Bove T, Zangrillo A, Guarracino F, Alvaro G, Persi B, Maglioni E, Galdieri N, Comis M, Caramelli F, Pasero DC, Pala G, Renzini M, Conte M, Paternoster G, Martinez B, Pinelli F, Frontini M, Zucchetti MC, Pappalardo F, Amantea B, Camata A, Pisano A, Verdecchia C, Dal Checco E, Cariello C, Faita L, Baldassarri R, Scandroglio AM, Saleh O, Lembo R, Calabro MG, Bellomo R, Landoni G. Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial. JAMA. 2014;312:2244–2253. doi: 10.1001/jama.2014.13573.
    1. Dardashti A, Ederoth P, Algotsson L, Bronden B, Grins E, Larsson M, Nozohoor S, Zinko G, Bjursten H. Erythropoietin and protection of renal function in cardiac surgery (the EPRICS Trial) Anesthesiology. 2014;121:582–590. doi: 10.1097/ALN.0000000000000321.
    1. KDIGO AKI Work Group (2012) KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2(1):1–138
    1. Chawla LS, Goldstein SL, Kellum JA, Ronco C. Renal angina: concept and development of pretest probability assessment in acute kidney injury. Crit Care. 2015;19:93. doi: 10.1186/s13054-015-0779-y.
    1. Ronco C, Kellum JA, Haase M. Subclinical AKI is still AKI. Crit Care. 2012;16:313. doi: 10.1186/cc11426.
    1. Endre ZH, Walker RJ, Pickering JW, Shaw GM, Frampton CM, Henderson SJ, Hutchison R, Mehrtens JE, Robinson JM, Schollum JB, Westhuyzen J, Celi LA, McGinley RJ, Campbell IJ, George PM. Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial) Kidney Int. 2010;77:1020–1030. doi: 10.1038/ki.2010.25.
    1. 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, Rimmele 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:R25. doi: 10.1186/cc12503.
    1. Meersch M, Schmidt C, Van Aken H, Martens S, Rossaint J, Singbartl K, Gorlich 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:e93460. doi: 10.1371/journal.pone.0093460.
    1. Katz N, Ronco C. Acute kidney stress—a useful term based on evolution in the understanding of acute kidney injury. Crit Care. 2016;20:23. doi: 10.1186/s13054-016-1184-x.
    1. Zhong W, Yang X, Yan H, Zhang X, Su J, Chen Z, Liao R, Nie Q, Dong S, Zhou Q, Yang J, Tu H, Wu YL. Phase II study of biomarker-guided neoadjuvant treatment strategy for IIIA-N2 non-small cell lung cancer based on epidermal growth factor receptor mutation status. J Hematol Oncol. 2015;8:54. doi: 10.1186/s13045-015-0151-3.
    1. Bhardwaj A, Rehman SU, Mohammed AA, Gaggin HK, Barajas L, Barajas J, Moore SA, Sullivan D, Januzzi JL. Quality of life and chronic heart failure therapy guided by natriuretic peptides: results from the ProBNP outpatient tailored chronic heart failure therapy (PROTECT) study. Am Heart J. 2012;164(793–799):e791.
    1. Ronco C, McCullough PA, Chawla LS. Kidney attack versus heart attack: evolution of classification and diagnostic criteria. Lancet. 2013;382:939–940. doi: 10.1016/S0140-6736(13)61932-7.
    1. Ronco C. Acute kidney injury: from clinical to molecular diagnosis. Crit Care. 2016;20:201. doi: 10.1186/s13054-016-1373-7.
    1. Zarbock A, Kellum JA, Schmidt C, Van Aken H, Wempe C, Pavenstadt H, Boanta A, Gerss J, Meersch M. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury: the ELAIN randomized clinical trial. JAMA. 2016;315:2190–2199. doi: 10.1001/jama.2016.5828.
    1. Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, Pepper J, Robertson S, Xenou M, Clayton T, Yellon DM, Investigators ET. Remote ischemic preconditioning and outcomes of cardiac surgery. N Engl J Med. 2015;373:1408–1417. doi: 10.1056/NEJMoa1413534.
    1. Billings FT, Hendricks PA, Schildcrout JS, Shi Y, Petracek MR, Byrne JG, Brown NJ. High-dose perioperative atorvastatin and acute kidney injury following cardiac surgery: a randomized clinical trial. JAMA. 2016;315:877–888. doi: 10.1001/jama.2016.0548.
    1. 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. Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. JAMA. 2015;313:2133–2141. doi: 10.1001/jama.2015.4189.
    1. Coca SG, Garg AX, Swaminathan M, Garwood S, Hong K, Thiessen-Philbrook H, Passik C, Koyner JL, Parikh CR, TRIBE-AKI Consortium Preoperative angiotensin-converting enzyme inhibitors and angiotensin receptor blocker use and acute kidney injury in patients undergoing cardiac surgery. Nephrol Dial Transplant. 2013;28:2787–2799. doi: 10.1093/ndt/gft405.
    1. Ingels C, Derese I, Wouters PJ, Van den Berghe G, Vanhorebeek I. Soluble RAGE and the RAGE ligands HMGB1 and S100A12 in critical illness: impact of glycemic control with insulin and relation with clinical outcome. Shock. 2015;43:109–116. doi: 10.1097/SHK.0000000000000278.
    1. Garg R, Grover A, McGurk S, Rawn JD. Predictors of hyperglycemia after cardiac surgery in nondiabetic patients. J Thorac Cardiovasc Surg. 2013;145:1083–1087. doi: 10.1016/j.jtcvs.2012.07.089.
    1. Osawa EA, Rhodes A, Landoni G, Galas FR, Fukushima JT, Park CH, Almeida JP, Nakamura RE, Strabelli TM, Pileggi B, Leme AC, Fominskiy E, Sakr Y, Lima M, Franco RA, Chan RP, Piccioni MA, Mendes P, Menezes SR, Bruno T, Gaiotto FA, Lisboa LA, Dallan LA, Hueb AC, Pomerantzeff PM, Kalil Filho R, Jatene FB, Auler Junior JO, Hajjar LA. Effect of perioperative goal-directed hemodynamic resuscitation therapy on outcomes following cardiac surgery: a randomized clinical trial and systematic review. Crit Care Med. 2016;44:724–733.
    1. Schetz M, Vanhorebeek I, Wouters PJ, Wilmer A, Van den Berghe G. Tight blood glucose control is renoprotective in critically ill patients. J Am Soc Nephrol. 2008;19:571–578. doi: 10.1681/ASN.2006101091.
    1. Kolhe NV, Staples D, Reilly T, Merrison D, McIntyre CW, Fluck RJ, Selby NM, Taal MW. Impact of compliance with a care bundle on acute kidney injury outcomes: a prospective observational study. PLoS One. 2015;10:e0132279. doi: 10.1371/journal.pone.0132279.
    1. Kolhe NV, Reilly T, Leung J, Fluck RJ, Swinscoe KE, Selby NM, Taal MW. A simple care bundle for use in acute kidney injury: a propensity score matched cohort study. Nephrol Dial Transplant. 2016;11:1846. doi: 10.1093/ndt/gfw087.
    1. Thakar CV, Kharat V, Blanck S, Leonard AC. Acute kidney injury after gastric bypass surgery. Clin J Am Soc Nephrol. 2007;2:426–430. doi: 10.2215/CJN.03961106.
    1. Koyner JL, Shaw AD, Chawla LS, Hoste EA, Bihorac A, Kashani K, Haase M, Shi J, Kellum JA, Sapphire I. Tissue inhibitor metalloproteinase-2 (TIMP-2) IGF-binding protein-7 (IGFBP7) levels are associated with adverse long-term outcomes in patients with AKI. J Am Soc Nephrol. 2015;26:1747–1754. doi: 10.1681/ASN.2014060556.
    1. Rifkin DE, Coca SG, Kalantar-Zadeh K. Does AKI truly lead to CKD? J Am Soc Nephrol. 2012;23:979–984. doi: 10.1681/ASN.2011121185.
    1. Kellum JA, Sileanu FE, Murugan R, Lucko N, Shaw AD, Clermont G. Classifying AKI by urine output versus serum creatinine level. J Am Soc Nephrol. 2015;26:2231–2238. doi: 10.1681/ASN.2014070724.
    1. McIlroy DR, Argenziano M, Farkas D, Umann T, Sladen RN. Incorporating oliguria into the diagnostic criteria for acute kidney injury after on-pump cardiac surgery: impact on incidence and outcomes. J Cardiothorac Vasc Anesth. 2013;27:1145–1152. doi: 10.1053/j.jvca.2012.12.017.
    1. Levy MM, Pronovost PJ, Dellinger RP, Townsend S, Resar RK, Clemmer TP, Ramsay G. Sepsis change bundles: converting guidelines into meaningful change in behavior and clinical outcome. Crit Care Med. 2004;32:S595–S597. doi: 10.1097/01.CCM.0000147016.53607.C4.
    1. Djurkovic S, Baracaldo JC, Guerra JA, Sartorius J, Haupt MT. A survey of clinicians addressing the approach to the management of severe sepsis and septic shock in the United States. J Crit Care. 2010;25(658):e651–e656.

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