STELLAR — SGLT2i Treatment to Explore Link of Long-term and Acute Renoprotection
If SGLT2 inhibitors prevent acute kidney injury after cardiac surgery, do they also prevent the chronic kidney disease that so often follows it? STELLAR proposes a new functional test — a “VO2 max for the kidney” — sensitive enough to catch decline before conventional criteria can.
Status: this is a full proposal to the Dutch Kidney Foundation’s Kolff+ programme (Junior Talent Grant), presented to the review board in June 2026. A funding decision is expected soon — this page will be updated once it’s confirmed.
The problem
CSA-AKI affects up to 60% of major cardiac surgery patients, and survivors carry a substantially elevated long-term risk of chronic kidney disease. Two gaps stand in the way of doing anything about it. First, CKD is only diagnosed once eGFR has fallen below 60 ml/min/1.73m² for three months, or albuminuria is persistent — by which point substantial, irreversible nephron loss has already occurred. Second, creatinine and eGFR often return to apparent baseline soon after surgery, so at-risk patients are discharged without structured renal follow-up, and the window for intervening is missed entirely.
Functional Renal Reserve Capacity
FRRC can be thought of as a VO2 max test for the kidney. After an oral protein load, healthy kidneys raise perfusion and glomerular filtration to clear the extra amino acids — the size of that response is the “reserve.” STELLAR measures FRRC using renal MRI (ASL and BOLD sequences) and measured GFR, before and after a standardised protein load, at baseline (one week before surgery) and again 4–12 weeks afterwards. The hypothesis: a postoperative drop in FRRC signals subclinical nephron loss long before conventional CKD criteria would catch it — and predicts eGFR decline at one and two years.
Design
Adults aged ≥65 with at least one AKI risk factor (chronic kidney disease, diabetes, hypertension, heart failure, vascular disease, COPD, anaemia, or obesity) undergoing elective open cardiac surgery are randomised 1:1 to dapagliflozin or standard care, starting one week before surgery and continuing for three weeks after. FRRC is assessed at baseline and at weeks 4–12; kidney function is then followed for two years, with outcome assessments at weeks 52 and 104, to determine eGFR trajectory and CKD incidence. The trial targets 58 participants (24 per group, plus 20% for attrition).
Hypotheses
- Primary: postoperative reductions in FRRC — driven by perioperative AKI — predict subsequent eGFR decline or progression to CKD.
- The magnitude of FRRC change correlates with the incidence and severity of AKI.
- SGLT2i treatment attenuates FRRC reductions by preventing AKI in the first place.
- Preoperative FRRC itself predicts risk of perioperative AKI and later CKD or eGFR decline.
Team
Where this leads
STELLAR is the direct long-term follow-on to MERCURI-2, using the same trial network and referral pathways through the cardiac surgery outpatient clinic. If confirmed, it would provide the first prospective evidence that preventing AKI with SGLT2i also preserves long-term kidney health.