ELECTRIC — Efficacy of Leveraging Endocrine Therapies for Renoprotection during Intensive Care
A three-year Global Individual Fellowship testing two new renoprotective agents — GLP-1 receptor agonists and SGLT2 inhibitors — across preclinical, imaging, and clinical settings, spanning Melbourne, Amsterdam, and a secondment at VUmc.
Funded by the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement No. 101024833. Results are published as they clear peer review; embargoed data will be added here on publication.
The problem
AKI affects over half of ICU patients, with high short-term mortality and long-term progression to chronic kidney disease. Beyond restoring normal physiology and avoiding nephrotoxins, no specific renoprotective therapy exists for the critically ill. Two endocrine agents now show encouraging renoprotective signals for reasons independent of glucose-lowering: GLP-1 receptor agonists and SGLT2 inhibitors. ELECTRIC set out to test both, and to validate urinary oxygenation (PuO2) as an early, continuous way of detecting the kidney distress that precedes a rise in creatinine.
Research plan
Central hypothesis: GLP-1 receptor activation and SGLT2 inhibition reduce markers of AKI in critically ill patients. Four research objectives, plus one translational objective on PuO2, were split across five work packages:
- WP1 — Ovine model (Royal Melbourne Hospital / Florey Institute): quantify the effect of GLP-1 and SGLT2i on kidney perfusion, oxygenation, and injury markers in an ovine model of septic-shock-associated AKI.
- WP2 — Sepsis, ICU (Royal Melbourne Hospital): effect of GLP-1 RA and SGLT2i on AKI markers in patients admitted to intensive care with sepsis.
- WP3 — Healthy-volunteer imaging (VUmc secondment): evaluate SGLT2 inhibition’s effect on kidney perfusion and oxygenation using PET-CT and BOLD-MRI.
- WP4 — Cardiac surgery (Amsterdam UMC, Rembrandt Institute): effect of GLP-1 RA and SGLT2i on AKI markers in patients undergoing cardiovascular surgery.
- WP5 — Integration: combine outcome parameters across all work packages to validate PuO2 as an early detector of AKI.
Outcomes & what it enabled
ELECTRIC’s clinical cardiac-surgery arm (WP4) matured directly into the MERCURI trials testing SGLT2 inhibition against postoperative AKI, and its urinary-oxygenation methodology now runs through NEPTUNE. Individual results from each work package are published as they clear peer review; see Publications for the current list.
Team & collaborators
Conducted across three institutions: the Royal Melbourne Hospital and Florey Institute (preclinical model and clinical sepsis cohort, with Prof. Rinaldo Bellomo and Prof. Adam Deane), VUmc (renal PET-CT and BOLD-MRI imaging), and the Rembrandt Institute at Amsterdam UMC (cardiac surgery cohort, with Prof. Markus Hollmann and Prof. Jeroen Hermanides).
Where this leads
ELECTRIC is the direct continuation of my Rubicon fellowship in the same Melbourne network, and fed forward into the MERCURI trials and NEPTUNE on returning to Amsterdam.