AKI
Bilateral / unilateral ischemia-reperfusion injury (IRI)
The reference model of ischemic acute kidney injury, used for both early injury and the transition to chronic kidney disease.
Background and rationale
Warm ischemia followed by reperfusion reproduces the tubular injury seen in cardiac surgery, shock and kidney transplantation. Bilateral clamping gives a robust, reproducible rise in plasma creatinine and BUN within 24 hours, while unilateral clamping (with or without delayed contralateral nephrectomy) allows the study of maladaptive repair, inflammation and fibrosis without lethal uremia.
Typical study design
- Randomisation to sham, vehicle and treatment arms with blinded surgery and analysis
- Temperature-controlled clamping of the renal pedicle, ischemia time titrated to the desired severity
- Dosing before ischemia, at reperfusion or delayed, depending on the therapeutic hypothesis
- Serial plasma and urine sampling with terminal tissue collection
Readouts
- Plasma creatinine, BUN and cystatin C
- Urinary NGAL, Kim-1 and albumin-creatinine ratio
- Histology (HE, PAS, Sirius red) with AI-assisted tubular injury and fibrosis scoring
- Immunohistochemistry and multiplex immunofluorescence for injury, immune cell and fibrosis markers
- Bulk and single nuclei RNA sequencing, spatial transcriptomics
- Transdermal GFR (MediBeacon) and resazurin tubular function assay
Interested in this model?
We will walk you through severity levels, group sizes, dosing windows and endpoints, and propose a design matched to your compound.