Effects of Different Doses of Remote Ischemic Preconditioning on Kidney Damage Among Patients Undergoing Cardiac Surgery: A Single-Center Mechanistic Randomized Controlled Trial. Issue 8 (August 2020)

• Record Type: Journal Article
• Authors: Meersch, Melanie; Küllmar, Mira; Pavenstädt, Hermann; Rossaint, Jan; Kellum, John A.; Martens, Sven; Klausmeyer, Pia; Schmidt, Elisa A.; Kerschke, Laura; Zarbock, Alexander
• Is Part Of: Critical care medicine. Volume 48:Issue 8(2020)
• Publication Date: 2020-08
• Subjects: biomarkers -- high-mobility group box 1 -- insulin-like growth factor–binding protein 7 -- myoglobin -- tissue inhibitor of metalloproteinases-2; Critical care medicine -- Periodicals; Soins intensifs -- Périodiques; 616.028
• DOI: 10.1097/CCM.0000000000004415
• Languages: English
• ISSNs: 0090-3493

Abstract

Abstract : Objectives: We have previously shown that remote ischemic preconditioning reduces acute kidney injury (acute kidney injury) in high-risk patients undergoing cardiopulmonary bypass and that the protective effect is confined to patients who exhibit an increased urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor–binding protein 7 in response to remote ischemic preconditioning. The purpose of this study was to determine the optimal intensity of remote ischemic preconditioning to induce required [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor–binding protein 7] changes and further explore mechanisms of remote ischemic preconditioning. Design: Observational and randomized controlled, double-blind clinical trial. Setting: University Hospital of Muenster, Germany. Patients: High-risk patients undergoing cardiac surgery as defined by the Cleveland Clinic Foundation Score. Interventions: In the interventional part, patients were randomized to receive either one of four different remote ischemic preconditioning doses (3 × 5 min, 3 × 7 min, 3 × 10 min remote ischemic preconditioning, or 3 × 5 min remote ischemic preconditioning + 2 × 10 min remote ischemic preconditioning in nonresponders) or sham-remote ischemic preconditioning (control). Measurements and Main Results: The primary endpoint of the interventional part was change in urinary [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor–binding protein 7] between pre- and postintervention. To examine secondary objectives including acute kidney injury incidence, we included an observational cohort. A total of 180 patients were included in the trial ( n = 80 observational and n = 100 randomized controlled part [20 patients/group]). The mean age was 69.3 years (10.5 yr), 119 were men (66.1%). Absolute changes in [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor–binding protein 7] were significantly higher in all remote ischemic preconditioning groups when compared with controls ( p < 0.01). Although we did not observe a dose-response relationship on absolute changes in [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor–binding protein 7] across the four different remote ischemic preconditioning groups, in the 15 patients failing to respond to the lowest dose, nine (60%) responded to a subsequent treatment at a higher intensity. Compared with controls, fewer patients receiving remote ischemic preconditioning developed acute kidney injury within 72 hours after surgery as defined by both Kidney Disease: Improving Global Outcomes criteria (30/80 [37.5%] vs 61/100 [61.0%]; p = 0.003). Conclusions: All doses of remote ischemic preconditioning significantly increased [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor–binding protein 7] and significantly decreased acute kidney injury compared with controls. High-dose remote ischemic preconditioning could stimulate [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor–binding protein 7] increases in patients refractory to low-dose remote ischemic preconditioning. Abstract : Supplemental Digital Content is available in the text.