Prevention of Cardiac Surgery–Associated Acute Kidney Injury by Implementing the KDIGO Guidelines in High-Risk Patients Identified by Biomarkers

The PrevAKI-Multicenter Randomized Controlled Trial

Alexander Zarbock, MD; Mira Küllmar, MD; Marlies Ostermann, MD; Gianluca Lucchese, MD; Kamran Baig, MD; Armando Cennamo, MD; Ronak Rajani, MD; Stuart McCorkell, MD; Christian Arndt, MD; Hinnerk Wulf, MD; Marc Irqsusi, MD; Fabrizio Monaco, MD; Ambra Licia Di Prima, MD; Mercedes García Alvarez, MD; Stefano Italiano, MD; Jordi Miralles Bagan, MD; Gudrun Kunst, MD; Shrijit Nair, MD; Camilla L'Acqua, MD; Eric Hoste, MD; Wim Vandenberghe, MD; Patrick M. Honore, MD; John A. Kellum, MD; Lui G. Forni, MD; Philippe Grieshaber, MD; Christina Massoth, MD; Raphael Weiss, MD; Joachim Gerss, PhD; Carola Wempe, PhD; Melanie Meersch, MD


Anesth Analg. 2021;133(2):292-302. 

In This Article

Abstract and Introduction


Background: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial.

Methods: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor–binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI.

Results: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6–69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR −4.8% [95% CI, −16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9–19.1]; P = .034). There were no significant effects on other specified secondary outcomes.

Conclusions: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group.


Acute kidney injury (AKI) is one of the most common and challenging complications in the perioperative period with significant effects on both short- and long-term outcomes. In particular, patients undergoing cardiac surgery are predisposed to develop this clinical syndrome with reported rates approaching 80%.[1] Depending on the severity of AKI, hospital mortality can be as high as 46.7%.[2] Furthermore, AKI is known to be associated with other complications, including infection, bleeding, delirium, chronic cardiovascular diseases, chronic kidney disease (CKD), and chronic dialysis dependency.[3] The pathophysiology of cardiac surgery–associated AKI (CSA-AKI) is complex and not fully understood, although the use of cardiopulmonary bypass (CPB) contributes to the development of CSA-AKI through inducing ischemia-reperfusion-injury as well as inflammatory response.[4] The lack of specific treatment options for CSA-AKI highlights the need for preventive strategies.[5]

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for AKI recommend the initiation of a bundle of supportive measures in patients at high risk for AKI.[6] This bundle consists of avoidance of all nephrotoxic agents, prevention of hyperglycemia, optimization of hemodynamics and perfusion pressure, functional hemodynamic monitoring if necessary, and close monitoring of renal function. Identification of patients at high risk for AKI can be achieved through the use of biomarkers, including the markers of renal stress associated with cell cycle arrest, tissue inhibitor of metalloproteinases-2 (TIMP-2), and insulin growth factor–binding protein 7 (IGFBP7).[7,8] Their advantage is that they are able to detect kidney stress before damage or loss of function, allowing the initiation of therapy much earlier compared to management guided by the functional biomarkers serum creatinine and urine output.[9,10] Two single-center randomized controlled trials using a biomarker-based approach demonstrated that the implementation of a bundle of supportive measures significantly reduced the occurrence of AKI in patients undergoing cardiac and major abdominal surgery.[11,12] In addition, a quality improvement initiative supports the results of these small randomized controlled trials.[13] Therefore, a large definitive multicenter randomized controlled trial is needed to confirm these findings. In preparation, we performed a multicenter, multinational, randomized controlled trial to investigate the adherence to the study protocol including biomarker-guided implementation of the KDIGO bundle.