Impact of propofol or sevoflurane on the renoprotective effect of remote ischaemic preconditioning in cardiac surgery: the HypnoRenalRIP randomised clinical trial

Abstract

Background: Remote ischaemic preconditioning (RIPC) might reduce acute kidney injury after cardiac surgery. Protective effects appear to be restricted to patients with early and transient increases in two cell cycle arrest markers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), in urine. Studies suggest that propofol can attenuate the preconditioning effect on the myocardium. This study investigated whether propofol diminishes the renoprotective effect associated with the early transient increases in TIMP-2 and IGFBP7.

Methods: This was a single-centre, prospective randomised double-blind 2×2 factorial clinical trial of high-risk patients undergoing cardiac surgery. Patients were randomised to receive either propofol+sham-RIPC, propofol+RIPC, sevoflurane+sham-RIPC, or sevoflurane+RIPC. The primary outcome measure was the change in the product of urinary concentrations of TIMP-2 and IGFBP7 ([TIMP-2]·[IGFBP7]) from before to after the intervention.

Results: We enrolled 160 participants in the trial (propofol+sham-RIPC: n=20, propofol+RIPC: n=60, sevoflurane+sham-RIPC: n=20, sevoflurane+RIPC: n=60). The median change in [TIMP-2]·[IGFBP7] as an indicator of response to RIPC was greater in participants receiving sevoflurane (0.070; interquartile range, -0.120 to 0.418) compared with those receiving propofol (-0.015; interquartile range, -0.138 to 0.068; P=0.022). Conversely, elevated [TIMP-2]·[IGFBP7] as a sign of renal stress in response to surgery was detected in all groups except for sevoflurane+RIPC (P=0.001). There were no statistically significant differences in patient-centred outcomes between groups.

Conclusions: Transient increases in [TIMP-2]·[IGFBP7] induced by RIPC, which were associated with renoprotective effects, were only seen with sevoflurane anaesthesia, but not when propofol was used. The association of biomarker concentrations and choice of anaesthetic agent suggests that propofol can attenuate the renoprotective effects of remote ischaemic preconditioning.

Clinical trial registration: DRKS00014989.

Keywords: acute kidney injury; biomarker; cardiac surgery; insulin-like growth factor-binding protein 7; propofol; remote ischaemic preconditioning; tissue inhibitor of metalloproteinases-2.