Abstract for presentation at Australia and New Zealand Society of Nephrology Annual Scientific Conference

Ischaemia-reperfusion (IR) injury is an important cause of acute kidney failure and contributes to reduced survival of renal allografts. Tissue factor (TF), thrombin and protease activated receptor-1 (PAR–1, a thrombin receptor) all contribute to renal IR injury. TF consists of an extra-cellular (procoagulant domain) and a cytoplasmic domain. The cytoplasmic domain may signal via a PAR-2 dependent pathway.
Employing our established model of renal IR injury (bilateral renal pedicle occlusion for 25 minutes and varying periods of reperfusion) we now demonstrate that mice lacking the cytoplasmic domain of TF (TF) develop more severe renal failure at both 24 and 48 hours post reperfusion than wild-type (WT) mice (creatinine 194±13.3µmol/L vs. 124±17.6µmol/L and 216.0±32.7µmol/L vs. 92.8±43.2µmol/L, TF vs. WT; p=0.01 and p=0.02 at 24 and 48 h respectively). At 24 hours TF mice had relatively increased levels of IL-6 mRNA (3.90±0.85 vs. 1.15±1.25, TF vs. WT; p=0.01) with a trend to increased levels of IL-18 mRNA. PAR-1 expression was increased in TF mice at 24 hours (2.01±0.37 vs. 0.32±00.05, TF vs. sham; p=0.008) to a greater degree than WT controls. Renal TF activity in TF and WT controls was not different. Absence of the TF cytoplasmic domain did not appear to be acting by PAR-2 signalling as PAR-2 and WT control developed equal levels of renal impairment. Our data suggests that at least in the kidney, the cytoplasmic domain of TF may be anti-inflammatory by regulating PAR-1 and IL-18 expression and may protect against renal injury following IR.

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