Preoperative Short-Term Calorie Restriction for Prevention of Acute Kidney Injury After Cardiac Surgery: A Randomized, Controlled, Open-Label, Pilot Trial

Franziska Grundmann, Roman-Ulrich Müller, Annika Reppenhorst, Lennart Hülswitt, Martin R Späth, Torsten Kubacki, Maximilian Scherner, Michael Faust, Ingrid Becker, Thorsten Wahlers, Bernhard Schermer, Thomas Benzing, Volker Burst, Franziska Grundmann, Roman-Ulrich Müller, Annika Reppenhorst, Lennart Hülswitt, Martin R Späth, Torsten Kubacki, Maximilian Scherner, Michael Faust, Ingrid Becker, Thorsten Wahlers, Bernhard Schermer, Thomas Benzing, Volker Burst

Abstract

Background: Acute kidney injury is a frequent complication after cardiac surgery and is associated with adverse outcomes. Although short-term calorie restriction (CR) has proven protective in rodent models of acute kidney injury, similar effects have not yet been demonstrated in humans.

Methods and results: CR_KCH (Effect of a Preoperative Calorie Restriction on Renal Function After Cardiac Surgery) is a randomized controlled trial in patients scheduled for cardiac surgery. Patients were randomly assigned to receive either a formula diet containing 60% of the daily energy requirement (CR group) or ad libitum food (control group) for 7 days before surgery. In total, 82 patients were enrolled between April 16, 2012, and February 5, 2015. There was no between-group difference in the primary end point of median serum creatinine increment after 24 hours (control group: 0.0 mg/dL [-0.1 - (+0.2) mg/dL]; CR group: 0.0 mg/dL [-0.2 - (+0.2) mg/dL]; P=0.39). CR prevented a rise in median creatinine at 48 hours (control group: +0.1 mg/dL [0.0 - 0.3 mg/dL]; CR group: -0.1 mg/dL [-0.2 - (+0.1) mg/dL]; P=0.03), with most pronounced effects observed in male patients and patients with a body mass index >25. This benefit persisted until discharge: Median creatinine decreased by 0.1 mg/dL (-0.2 - 0.0 mg/dL) in the CR group, whereas it increased by 0.1 mg/dL (0.0 - 0.3 mg/dL; P=0.0006) in the control group. Incidence of acute kidney injury was reduced by 5.8% (41.7% in the CR group compared with 47.5% in the control group). Safety-related events did not differ between groups.

Conclusions: Despite disappointing results with respect to creatinine rise within the first 24 hours, the benefits observed at later time points and the subgroup analyses suggest the protective potential of short-term CR in patients at risk for acute kidney injury, warranting further investigation.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01534364.

Keywords: acute kidney injury; calorie restriction; cardiac surgery; dietary restriction; preconditioning.

© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1
Figure 1
Patient flow and randomization. CR indicates calorie reduction.
Figure 2
Figure 2
Intention‐to‐treat analysis. Evolution of serum creatinine from baseline to 24 hours after cross‐clamping (primary end point) and from baseline to 48 hours after cross‐clamping and maximum increase of serum creatinine within 48 hours after cross‐clamping in CR patients (white boxes, dashed line; n=36) and control patients (gray boxes, solid line; n=40). A, Box plots showing the change of serum creatinine from baseline to specified time points. B, Development of mean (±SEM) serum creatinine from baseline (0 hour) to 48 hours after cross‐clamping.
Figure 3
Figure 3
Subgroup analyses showing impact of sex (A, upper panel), body mass index (BMI; A, lower panel) and chronic kidney disease (CKD) stages (B). A, Male participants: calorie reduction (CR) group (white boxes), 29 of 36 participants; control group (gray boxes), 31 of 40 participants. BMI >25: CR group, 22 of 36 participants; control group, 30 of 40 participants. B, CKD 1: CR group (white boxes), n=3; control group (gray boxes), n=5. CKD 2: CR group, n=15; control group, n=13. CKD 3: CR group, n=13; control group, n=20. CKD 4: CR group, n=2; control group, n=1. Box plots showing the change of serum creatinine from baseline to specified time points.
Figure 4
Figure 4
Per‐protocol analysis. Evolution of serum creatinine from baseline to 24 hours after cross‐clamping (primary end point) and from baseline to 48 hours after cross‐clamping and the maximum increase of serum creatinine within 48 hours after cross‐clamping in CR patients (white boxes, dashed line, n=13) and control patients (gray boxes, solid line, n=11). A, Box plots showing the change of serum creatinine from baseline to specified time points. B, Development of mean (±SEM) serum creatinine from baseline (0 hour) to 48 hours after cross‐clamping.

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