Rationale: Ischemia reperfusion (I/R) injury still remains one of main causes of early renal dysfunction in kidney transplantation. There are no effective treatments for preventing I/R injury.

Objectives: This study aims to investigate the impact of a new molecule growth differentiation factor 15 (GDF15) in I/R injury in kidney transplantation.

Methods and Results: A murine warm I/R injury model in which left renal artery and vein of mice were clamped and collateral kidney was removed at the beginning of reperfusion. Renal function and histopathological change were measured 24h after reperfusion. Cell apoptosis and gene expression were detected by TUNEL and qRT-PCR, respectively. The effect of GDF15 on renal cell death was assessed using tubular cells in vitro. Results showed that GDF15 transgenic mice who over-expressed GDF15 had the lowest levels of blood creatinine and BUN, while GDF15 knockout mice had the highest levels of creatinine and BUN. Only one out of six C57Bl/L6 wild type mice survived over 8 days while other mice died within 3 days. All GDF15 knockout mice died next day post I/R. In contrast, four of eight GDF15 mice survived over 8 days and none of GDF15 mice died on next day after clamping. Overexpression of GDF15 attenuated apoptosis in vivo and in vitro and reduced histopathological changes of kidney induced by I/R. The expression profile of circular RNA was changed among the groups.

Conclusion: Over-expression of GDF15 protects renal function from I/R injury, highlighting its therapeutic potential in preventing I/R injury in clinic.

CITATION INFORMATION: Zhu C., Patel A., Su Y., Jiang J., Lian D., Sener A., Min W., Luke P., Quan D., Liu K., Zheng X. GDF15 Preventing Renal Ischemia Reperfusion Injury Am J Transplant. 2017;17 (suppl 3).

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