MOLECULAR MECHANISMS OF DELAYED KIDNEY GRAFT FUNCTION

L. Rossard, F. Favreau, C. Nadeau, R. Thuillier, T. Hauet
Faculte De Medecine Et Pharmacie, Chu De Poitiers, Inserm U927, poitiers cedex/FRANCE

Body: Prupose : Renal ischemia reperfusion injury (IRI) influences early and long term graft outcome. Its severity correlates with chronic fibrosis and renal failure, but no accurate markers of IRI severity are available to guide diagnosis and therapy. Methods: We used a Large White pig kidney autotransplantation model. Kidneys underwent warm ischemia (WI, clamping for 60min), or cold storage (CS, 4°C preservation 24h in UW) or both (WI+CS). Results: Creatinemia analysis (Fig1) showed that WI+CS displayed the worst function at 3 days post reperfusion, followed by CS, and WI.
At this time, superoxide anion production is low in the WI group, high in CS and very high in WI+CS (Fig2).
Transcriptomics at day 3 (Figs 3 and 4) revealed that expression of oxidative stress markers p47phox, Nox2 was high in CS and higher in WI+CS. XHD is very low in WI and low in CS. In parallel, anti-oxidative stress markers Superoxide dismutase (SOD)-1 and 2 are decreased in the three groups, specifically in the WI+CS group. Heme-oxygenase 1 (HO-1) is high in the CS and WI+CS groups. HO-2 is decreased in the three groups but more so in the WI+CS group. Expression of inflammation markers TNFa, MCP-1, IL1b and IL1Rn increases progressively with IRI severity. IL6 and IL10 are high in CS and WI+CS groups. FoxP3 is decreased in all groups. Conclusion: Preliminary data show that injury severitydiscrimination seems possible at day 3 with Creatininemia, NADPH oxidase subunits, fluorimetric superoxide anion measurement, and some inflammation markers. We also uncovered several markers that did not appear discriminating. Such markers could represent critical assets to diagnose IRI severity and predict the outcome of transplanted kidneys.

Disclosure: All authors have declared no conflicts of interest.