Rubicon — NEPHRITIC: Nephroprotection through Incretin Therapy during Intensive Care
The fellowship that took me from PhD student to independent researcher: twelve months at the Royal Melbourne Hospital testing whether a gut hormone, GLP-1, could protect the kidney during critical illness — and the project that opened the door to everything that followed in kidney protection.
Status: completed December 2021. This fellowship established my Melbourne collaboration, preclinical model access, and urinary oxygenation (PuO2) methodology — the direct foundation for ELECTRIC, MERCURI-1/2, and NEPTUNE.
The problem
Over half of patients either have or develop acute kidney injury (AKI) during admission to an intensive care unit — associated with high short-term mortality and, in up to 30% of survivors, progression to end-stage renal disease. No specific renoprotective therapy existed for critically ill patients. I set out to test a new mechanism: activation of the glucagon-like peptide-1 (GLP-1) receptor, already known to slow chronic kidney disease in patients with diabetes through natriuresis-independent effects on glomerular pressure, inflammation, and oxidative stress — none of it yet tested against acute kidney injury.
Research plan
The central hypothesis: GLP-1 stimulation can reduce markers of AKI during critical illness. Three linked activities tested it from bench to bedside:
- Ovine septic shock model — an invasive, close-to-human sheep model of sepsis-associated AKI at the Royal Melbourne Hospital, quantifying the effect of GLP-1 on kidney perfusion, oxygenation, and injury biomarkers.
- Clinical study in septic ICU patients — building on ethical approval and funding already secured by my host supervisor, testing GLP-1’s effect on AKI markers in patients admitted to the ICU with sepsis.
- Systematic review of urinary oxygenation (PuO2) — an individual-subject-data meta-analysis validating this novel, real-time technique as an early indicator of renal distress, years before conventional markers like creatinine would detect it.
Outcomes & what it enabled
The fellowship gave me hands-on preclinical experience with the Melbourne ovine AKI model and direct exposure to urinary oxygenation monitoring — a technique I later implemented at Amsterdam UMC. As proposed from the outset, it was the explicit stepping stone to an NWO Veni application, and the collaboration it built directly produced ELECTRIC (the follow-on Marie Skłodowska-Curie fellowship) and, on return to Amsterdam, the MERCURI trials and NEPTUNE. The research focus itself later shifted from GLP-1 toward SGLT2 inhibition and ketone metabolism as the field’s evidence base evolved, but the methods and network established here underpin the entire kidney-protection line.
Team & collaborators
Funded by NWO through the Rubicon Talent Programme, administered by ZonMw. Findings were shared with the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS-CTG) and the Dutch Kidney Patients Association (NVN).
Where this leads
Rubicon was the seed for the entire kidney-protection line: it led directly to the ELECTRIC fellowship in the same Melbourne network, and — as planned from the start — to the NWO Veni grant that now funds NEPTUNE.