Renal ischaemia reperfusion injury (IRI) occurs during cardiac bypass, renal transplantation and severe hypovolaemia after trauma, causing acute kidney injury (AKI). There are currently no therapeutic options to ameliorate the injury. We have developed a murine IRI model which mimics the clinical situation, to determine the efficacy of stem cell based therapies. To longitudinally monitor efficacy of the therapies in preclinical studies we use a novel transcutaneous device which calculates the Glomerular Filtration Rate (GFR) based on FITC-Sinistrin clearance.
Aim: to track the change in GFR following IRI and identify modifiable factors which impact on injury.
Methods: 6 mice per group: bilateral renal pedicle clamping for 25, 27.5 and 30 minutes. Subsequent standardisation of anaesthetic time to 30 minutes before clamping for 27.5 minutes. 3 sham operations.
GFR: days 0, 1, 3, 7 and 14. Creatinine and BUN: day 14.
All data analysed using paired student t-tests and linear regression analysis. Significance level <0.05.
Results: GFR reduction was seen in all groups on day 1 and recovery in all by day 3. By day 14 there was no difference in GFR between injured and sham animals (p=0.05). Anaesthetic duration prior to clamping influenced GFR (p=0.02), regardless of clamp time (Figure 1). Standardising anaesthetic duration to 30 minutes reduced variance of FITC-Sinistrin clearance on day 1 (p=0.03) and day 3 (p=0.00), improving the reproducibility of magnitude of injury.
Conclusion: The effect of renal pedicle clamping on GFR not only depends on clamp time but additional factors including anaesthetic duration. Having demonstrated refinement of this model, we are now testing the potential of stem cell based therapies to reverse AKI. Transcutaneous FITC-Sinistrin clearance is a feasible, reliable and safe way to monitor renal function in rodents. This has the potential to be translated to human use, enabling real-time monitoring of GFR.