New model of renal warm ischaemia–reperfusion injury for comparative functional, morphological and pathophysiological studies

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Abstract
Background: Renal warm ischaemia–reperfusion injury is pertinent to vascular and transplant surgery. While established models provide functional and morphological data the authors wanted to be able to correlate this with the underlying pathophysiology at any chosen time point, thus allowing future interventional effects on reperfusion injury to be evaluated. Methods: In a rodent model bilateral renal warm ischaemia (15–60 min) and then reperfusion (20 or 80 min) before nephrectomy allowed for analysis of early reperfusion pathophysiology. The remaining kidney provided functional data (glomerular filtration rate (GFR)) at days 2 and 7 before nephrectomy for late analysis and morphology using a new grading system. Results: Acceptable survival rate (ten of 12 animals) was seen with up to 45 min of warm ischaemia. Renal function was impaired at day 2 following 30–60 min of warm ischaemia (P < 0·01) and day 7 in the 45- and 60-min groups (P < 0·05 and P < 0·01 respectively). Strong correlation existed between duration of ischaemia and GFR at day 2 (r2 = 0·88) and day 7 (r2 = 0·95). Histological damage in the cortical tubules was evident in the 45- and 60-min groups (P < 0·01). Conclusion: This new model allowed comparative functional, morphological and pathophysiological studies while minimizing the number of animals required. Overall 45 min of warm ischaemia gave significant, recoverable injury and is recommended for investigating renal reperfusion injury.