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


Enrolment and Patients

The trial was conducted between November 2017 and November 2019 in 12 centers in Germany, Belgium, Spain, Italy, and the United Kingdom. A total of 1447 patients were screened of whom 280 patients were enrolled and randomized to receive management according to the KDIGO bundle (n = 138) versus standard of care (n = 142). Two patients withdrew consent so that 278 patients were included in the final analysis (n = 136 intervention and n = 142 control group; Figure). The baseline and intraoperative characteristics did not differ between both groups (Table 1, Supplemental Digital Content, Table S2, Clinical care outside the trial intervention was also not different (Table 1, Supplemental Digital Content, Table S2, There were no significant differences in [TIMP-2]•[IGFBP7] values 4 hours after cardiac surgery.


Flow chart. Of 170 patients excluded for other reasons, 64 declined study participation, 56 had no written informed consent, no test was available in 15 cases, 12 could not be informed because of language barriers, 11 were based on clinical decision (eg, hematuria, methylene blue), 6 underwent emergency surgery, and 6 underwent reoperation before NC measurement. AKI indicates acute kidney injury; CKD, chronic kidney disease; GFR, glomerular filtration rate; NC, Nephrocheck; RRT, renal replacement therapy.

Primary Outcome

Compliance with the KDIGO recommendations was 65.4% in the intervention group (95% CI, 56.8–73.4) and 4.2% in the control group (95% CI, 1.6–9.0). Compliance was significantly better in the intervention group compared to the control group (absolute risk reduction [ARR], 61.2% [95% CI, 52.6–69.9]; P < .001; Table 2). Components of the KDIGO bundle were implemented more commonly in the intervention group compared to the control group (Supplemental Digital Content, Table S1,, discontinuation of nephrotoxic drugs: 98.5% vs 84.5%, P < .001; optimization of hemodynamic monitoring: 71.3% vs 53.5%, P = .002; close monitoring of kidney function: 91.2% vs 44.4%, P < .001; avoidance of hyperglycemia: 77.9% vs 24.6%, P < .001). However, the use of alternatives to radiocontrast agents (98.5% vs 97.2%; P = .440) and discontinuation of ACEi or ARBs (96.3% vs 90.5%; P = .064) were statistically not different between the groups (Table 2).

Measures During the Intervention Period

During the study period, significantly more patients in the intervention group received dobutamine compared to controls (32.6% vs 18.8%; P = .009) resulting in a significantly higher MAP at different time points (Table 3, Supplemental Digital Content, Table S3, In addition, patients assigned to the intervention group received significantly more crystalloids (P = .044; Table 3). However, transfusion rates were statistically not different in the 2 groups. Although the use of inotropes was significantly higher in the intervention group, there was no difference in the incidence of atrial fibrillation (Table 3).

Secondary Outcomes

The overall rate of AKI within 72 hours after cardiac surgery was statistically not different between the groups (46.3% intervention versus 41.5% control group; ARR −4.8% [95% CI, −16.4 to 6.9]; P = .423; Table 4, Supplemental Digital Content, Table S4, However, the occurrence of moderate to severe AKI (stage 2/3) 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 differences between the 2 groups in the secondary outcomes, including free days through day 28 of vasoactive medications and mechanical ventilation, renal recovery at days 30, 60, and 90, all-cause mortality at days 30, 60, and 90, length of stay in ICU and hospital, use of RRT at days 30 and 60, and MAKE90 (Table 4, Supplemental Digital Content, Table S5, However, use of RRT was higher in the intervention group at day 90 (3.3% intervention versus 0% control group; ARR, −3.3% [95% CI, −6.5 to −0.1]; P = .035).

Subgroup Analysis

Of 280 patients, 20 had a [TIMP-2]•[IGFBP7] concentration >2.0. In this subgroup, adherence with all components of the bundle was 84.6% in the intervention versus 0% in the control group. Moderate and severe AKI occurred in 23.1% randomized to the intervention compared to 71.4% in the control group. In contrast, in the low biomarker level subgroup, moderate and severe AKI developed in 13.0% of patients in the intervention and in 21.5% of the control group (Supplemental Digital Content, Tables S6, S7,