F YANG1,2, E OZOLS1, M JIANG2, F MA1, D NIKOLIC-PATERSON1, X JIANG2
1Monash Health, Clayton, Australia, 2Department of Pediatrics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Aim: To develop a simplified model of renal ischemia/reperfusion (I/R) injury.
Background: The transition of acute kidney injury (AKI) to chronic kidney disease is recognised as a major clinical problem. However, a limitation of current animal models of renal I/R injury is the requirement for near fatal injury for the subsequent development of renal fibrosis. Therefore, we investigated a modified gradient technique of I/R injury to facilitate the development of renal fibrosis while maintaining overall normal kidney function.
Methods: Groups of 6-8 male C57BL/6 mice were anaesthetised with sodium pentobarbital, the left kidney removed, and then a silk thread run under the lower renal branch and the right kidney raised under tension of a 20g weight using a pulley system for 30, 40 or 60min. Then the kidney was lowered, the wound sutured and intraperitoneal saline given. Groups of mice were killed after 1, 3, 7 or 28 days of reperfusion.
Results: In the raised kidney, the lower pole showed complete cessation of blood flow while the upper pole showed an incomplete cessation. An ischaemic period of 60min, but not 30 or 40min, induced significant renal impairment (187.0±65.3 vs 17.9±4.8 umol/L serum creatinine in normal; P<0.001). Tubular necrosis was more severe in the lower pole than the upper pole. Renal function returned to normal on day 3 and remained normal to day 28. On days 3 and 7, the lower pole showed more severe tubular damage compared to the upper pole, and on day 28 the lower pole showed substantial fibrosis whereas the upper pole was relatively normal.
Conclusion: We have developed a model of clinically “silent” renal fibrosis.
Ms Fan Yang is a medical graduate from China who is studying for a PhD in experimental kidney disease through the Department of Pediatrics at the The First Affiliated Hospital of Sun Yat-sen University in Guangzhou and in the Department of Nephrology at Monash Medical Centre. Fan is keen to develop a career as a clinician/scientist in the filed of Nephrology.