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Published in: Intensive Care Medicine 11/2017

Open Access 01-11-2017 | Seven-Day Profile Publication

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

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

Published in: Intensive Care Medicine | Issue 11/2017

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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.
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Literature
1.
go back to reference Hobson CE, Yavas S, Segal MS, Schold JD, Tribble CG, Layon AJ, Bihorac A (2009) Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation 119:2444–2453CrossRefPubMed Hobson CE, Yavas S, Segal MS, Schold JD, Tribble CG, Layon AJ, Bihorac A (2009) Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation 119:2444–2453CrossRefPubMed
2.
go back to reference 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 (2013) Reducing mortality in acute kidney injury patients: systematic review and international web-based survey. J Cardiothorac Vasc Anesth 27:1384–1398CrossRefPubMed 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 (2013) Reducing mortality in acute kidney injury patients: systematic review and international web-based survey. J Cardiothorac Vasc Anesth 27:1384–1398CrossRefPubMed
3.
go back to reference 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 (2014) Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial. JAMA 312:2244–2253CrossRefPubMed 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 (2014) Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial. JAMA 312:2244–2253CrossRefPubMed
4.
go back to reference Dardashti A, Ederoth P, Algotsson L, Bronden B, Grins E, Larsson M, Nozohoor S, Zinko G, Bjursten H (2014) Erythropoietin and protection of renal function in cardiac surgery (the EPRICS Trial). Anesthesiology 121:582–590CrossRefPubMed Dardashti A, Ederoth P, Algotsson L, Bronden B, Grins E, Larsson M, Nozohoor S, Zinko G, Bjursten H (2014) Erythropoietin and protection of renal function in cardiac surgery (the EPRICS Trial). Anesthesiology 121:582–590CrossRefPubMed
5.
go back to reference KDIGO AKI Work Group (2012) KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2(1):1–138 KDIGO AKI Work Group (2012) KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2(1):1–138
6.
go back to reference Chawla LS, Goldstein SL, Kellum JA, Ronco C (2015) Renal angina: concept and development of pretest probability assessment in acute kidney injury. Crit Care 19:93CrossRefPubMedPubMedCentral Chawla LS, Goldstein SL, Kellum JA, Ronco C (2015) Renal angina: concept and development of pretest probability assessment in acute kidney injury. Crit Care 19:93CrossRefPubMedPubMedCentral
8.
go back to reference 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 (2010) Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial). Kidney Int 77:1020–1030CrossRefPubMed 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 (2010) Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial). Kidney Int 77:1020–1030CrossRefPubMed
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, Rimmele T, Shapiro NI, Shaw AD, Shi J, Sprague AM, Vincent JL, Vinsonneau C, Wagner L, Walker MG, Wilkerson RG, Zacharowski K, Kellum JA (2013) Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care 17:R25CrossRefPubMedPubMedCentral 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 (2013) Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care 17:R25CrossRefPubMedPubMedCentral
10.
go back to reference Meersch M, Schmidt C, Van Aken H, Martens S, Rossaint J, Singbartl K, Gorlich D, Kellum JA, Zarbock A (2014) Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PLoS One 9:e93460CrossRefPubMedPubMedCentral Meersch M, Schmidt C, Van Aken H, Martens S, Rossaint J, Singbartl K, Gorlich D, Kellum JA, Zarbock A (2014) Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PLoS One 9:e93460CrossRefPubMedPubMedCentral
12.
go back to reference 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 (2015) 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 8:54CrossRefPubMedPubMedCentral 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 (2015) 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 8:54CrossRefPubMedPubMedCentral
13.
go back to reference Bhardwaj A, Rehman SU, Mohammed AA, Gaggin HK, Barajas L, Barajas J, Moore SA, Sullivan D, Januzzi JL (2012) 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 164(793–799):e791 Bhardwaj A, Rehman SU, Mohammed AA, Gaggin HK, Barajas L, Barajas J, Moore SA, Sullivan D, Januzzi JL (2012) 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 164(793–799):e791
14.
go back to reference Ronco C, McCullough PA, Chawla LS (2013) Kidney attack versus heart attack: evolution of classification and diagnostic criteria. Lancet 382:939–940CrossRefPubMed Ronco C, McCullough PA, Chawla LS (2013) Kidney attack versus heart attack: evolution of classification and diagnostic criteria. Lancet 382:939–940CrossRefPubMed
16.
go back to reference Zarbock A, Kellum JA, Schmidt C, Van Aken H, Wempe C, Pavenstadt H, Boanta A, Gerss J, Meersch M (2016) 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 315:2190–2199CrossRefPubMed Zarbock A, Kellum JA, Schmidt C, Van Aken H, Wempe C, Pavenstadt H, Boanta A, Gerss J, Meersch M (2016) 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 315:2190–2199CrossRefPubMed
17.
go back to reference 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 (2015) Remote ischemic preconditioning and outcomes of cardiac surgery. N Engl J Med 373:1408–1417CrossRefPubMed 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 (2015) Remote ischemic preconditioning and outcomes of cardiac surgery. N Engl J Med 373:1408–1417CrossRefPubMed
18.
go back to reference Billings FT, Hendricks PA, Schildcrout JS, Shi Y, Petracek MR, Byrne JG, Brown NJ (2016) High-dose perioperative atorvastatin and acute kidney injury following cardiac surgery: a randomized clinical trial. JAMA 315:877–888CrossRefPubMedPubMedCentral Billings FT, Hendricks PA, Schildcrout JS, Shi Y, Petracek MR, Byrne JG, Brown NJ (2016) High-dose perioperative atorvastatin and acute kidney injury following cardiac surgery: a randomized clinical trial. JAMA 315:877–888CrossRefPubMedPubMedCentral
19.
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 (2015) Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. JAMA 313:2133–2141CrossRefPubMed 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 (2015) Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. JAMA 313:2133–2141CrossRefPubMed
20.
go back to reference Coca SG, Garg AX, Swaminathan M, Garwood S, Hong K, Thiessen-Philbrook H, Passik C, Koyner JL, Parikh CR, TRIBE-AKI Consortium (2013) Preoperative angiotensin-converting enzyme inhibitors and angiotensin receptor blocker use and acute kidney injury in patients undergoing cardiac surgery. Nephrol Dial Transplant 28:2787–2799CrossRefPubMedPubMedCentral Coca SG, Garg AX, Swaminathan M, Garwood S, Hong K, Thiessen-Philbrook H, Passik C, Koyner JL, Parikh CR, TRIBE-AKI Consortium (2013) Preoperative angiotensin-converting enzyme inhibitors and angiotensin receptor blocker use and acute kidney injury in patients undergoing cardiac surgery. Nephrol Dial Transplant 28:2787–2799CrossRefPubMedPubMedCentral
21.
go back to reference Ingels C, Derese I, Wouters PJ, Van den Berghe G, Vanhorebeek I (2015) Soluble RAGE and the RAGE ligands HMGB1 and S100A12 in critical illness: impact of glycemic control with insulin and relation with clinical outcome. Shock 43:109–116CrossRefPubMed Ingels C, Derese I, Wouters PJ, Van den Berghe G, Vanhorebeek I (2015) Soluble RAGE and the RAGE ligands HMGB1 and S100A12 in critical illness: impact of glycemic control with insulin and relation with clinical outcome. Shock 43:109–116CrossRefPubMed
22.
go back to reference Garg R, Grover A, McGurk S, Rawn JD (2013) Predictors of hyperglycemia after cardiac surgery in nondiabetic patients. J Thorac Cardiovasc Surg 145:1083–1087CrossRefPubMed Garg R, Grover A, McGurk S, Rawn JD (2013) Predictors of hyperglycemia after cardiac surgery in nondiabetic patients. J Thorac Cardiovasc Surg 145:1083–1087CrossRefPubMed
23.
go back to reference 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 (2016) Effect of perioperative goal-directed hemodynamic resuscitation therapy on outcomes following cardiac surgery: a randomized clinical trial and systematic review. Crit Care Med 44:724–733PubMed 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 (2016) Effect of perioperative goal-directed hemodynamic resuscitation therapy on outcomes following cardiac surgery: a randomized clinical trial and systematic review. Crit Care Med 44:724–733PubMed
24.
go back to reference Schetz M, Vanhorebeek I, Wouters PJ, Wilmer A, Van den Berghe G (2008) Tight blood glucose control is renoprotective in critically ill patients. J Am Soc Nephrol 19:571–578CrossRefPubMedPubMedCentral Schetz M, Vanhorebeek I, Wouters PJ, Wilmer A, Van den Berghe G (2008) Tight blood glucose control is renoprotective in critically ill patients. J Am Soc Nephrol 19:571–578CrossRefPubMedPubMedCentral
25.
go back to reference Kolhe NV, Staples D, Reilly T, Merrison D, McIntyre CW, Fluck RJ, Selby NM, Taal MW (2015) Impact of compliance with a care bundle on acute kidney injury outcomes: a prospective observational study. PLoS One 10:e0132279CrossRefPubMedPubMedCentral Kolhe NV, Staples D, Reilly T, Merrison D, McIntyre CW, Fluck RJ, Selby NM, Taal MW (2015) Impact of compliance with a care bundle on acute kidney injury outcomes: a prospective observational study. PLoS One 10:e0132279CrossRefPubMedPubMedCentral
26.
go back to reference Kolhe NV, Reilly T, Leung J, Fluck RJ, Swinscoe KE, Selby NM, Taal MW (2016) A simple care bundle for use in acute kidney injury: a propensity score matched cohort study. Nephrol Dial Transplant 11:1846CrossRef Kolhe NV, Reilly T, Leung J, Fluck RJ, Swinscoe KE, Selby NM, Taal MW (2016) A simple care bundle for use in acute kidney injury: a propensity score matched cohort study. Nephrol Dial Transplant 11:1846CrossRef
27.
go back to reference Thakar CV, Kharat V, Blanck S, Leonard AC (2007) Acute kidney injury after gastric bypass surgery. Clin J Am Soc Nephrol 2:426–430CrossRefPubMed Thakar CV, Kharat V, Blanck S, Leonard AC (2007) Acute kidney injury after gastric bypass surgery. Clin J Am Soc Nephrol 2:426–430CrossRefPubMed
28.
go back to reference Koyner JL, Shaw AD, Chawla LS, Hoste EA, Bihorac A, Kashani K, Haase M, Shi J, Kellum JA, Sapphire I (2015) 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 26:1747–1754CrossRefPubMed Koyner JL, Shaw AD, Chawla LS, Hoste EA, Bihorac A, Kashani K, Haase M, Shi J, Kellum JA, Sapphire I (2015) 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 26:1747–1754CrossRefPubMed
30.
go back to reference Kellum JA, Sileanu FE, Murugan R, Lucko N, Shaw AD, Clermont G (2015) Classifying AKI by urine output versus serum creatinine level. J Am Soc Nephrol 26:2231–2238CrossRefPubMedPubMedCentral Kellum JA, Sileanu FE, Murugan R, Lucko N, Shaw AD, Clermont G (2015) Classifying AKI by urine output versus serum creatinine level. J Am Soc Nephrol 26:2231–2238CrossRefPubMedPubMedCentral
31.
go back to reference McIlroy DR, Argenziano M, Farkas D, Umann T, Sladen RN (2013) Incorporating oliguria into the diagnostic criteria for acute kidney injury after on-pump cardiac surgery: impact on incidence and outcomes. J Cardiothorac Vasc Anesth 27:1145–1152CrossRefPubMed McIlroy DR, Argenziano M, Farkas D, Umann T, Sladen RN (2013) Incorporating oliguria into the diagnostic criteria for acute kidney injury after on-pump cardiac surgery: impact on incidence and outcomes. J Cardiothorac Vasc Anesth 27:1145–1152CrossRefPubMed
32.
go back to reference Levy MM, Pronovost PJ, Dellinger RP, Townsend S, Resar RK, Clemmer TP, Ramsay G (2004) Sepsis change bundles: converting guidelines into meaningful change in behavior and clinical outcome. Crit Care Med 32:S595–S597CrossRefPubMed Levy MM, Pronovost PJ, Dellinger RP, Townsend S, Resar RK, Clemmer TP, Ramsay G (2004) Sepsis change bundles: converting guidelines into meaningful change in behavior and clinical outcome. Crit Care Med 32:S595–S597CrossRefPubMed
33.
go back to reference Djurkovic S, Baracaldo JC, Guerra JA, Sartorius J, Haupt MT (2010) A survey of clinicians addressing the approach to the management of severe sepsis and septic shock in the United States. J Crit Care 25(658):e651–e656 Djurkovic S, Baracaldo JC, Guerra JA, Sartorius J, Haupt MT (2010) A survey of clinicians addressing the approach to the management of severe sepsis and septic shock in the United States. J Crit Care 25(658):e651–e656
Metadata
Title
Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial
Authors
Melanie Meersch
Christoph Schmidt
Andreas Hoffmeier
Hugo Van Aken
Carola Wempe
Joachim Gerss
Alexander Zarbock
Publication date
01-11-2017
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 11/2017
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-016-4670-3

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