Bootcongres

Brain dead-derived kidney grafts have inferior transplantation outcomes compared to living donated kidneys. This is due to increased inflammation during the brain death (BD) period. Our previous studies show that cytoprotective heat shock proteins (HSP) are upregulated, but only at the end of the BD period. To reduce the BD-related kidney injury, we want to increase the HSP expression at the start of BD. Geranylgeranylacetone (GGA) is a drug known to induce HSP expression, however GGA is hydrophopic and therefore its use is limited to oral treatment. We investigated whether intravenous treatment (i.v.) with Nyk, a GGA derivate, can increase HSP expression, reduce the pro-inflammatory changes, and improve kidney donor quality in an in vivo brain death rat model. Male F344 rats (275-300g, n=34) underwent slow induction of brain death and were kept BD for 4 hours. We administered Nyk (0.5mg/kg iv), GGA (0.5 mg/kg iv) or a saline vehicle 20h and 0h prior to brain death induction. Renal Hsp72 protein expression was 0.99 [SE 0.08] in saline-, 2.14 [SE 0.54] in Nyk- (p-value: 0.064), and 1.05 [SE 0.14] in GGA-treated groups (p-value: 0.62) measured in fold induction (Hsp72/GAPDH).

Renal mRNA expression of the adhesion molecules E-selectin and ICAM-1 were respectively 1,11 [SE 0.13] and 0.76 [SE 0.07] in saline-, 0,58 [SE 0.08] and 0.48 [SE 0.07] in Nyk- (p-value <0.05), and 0.89 [SE 0.02] and 0.71 [SE 0.06] in GGA-treated groups (p-value <0.05) measured in fold induction (E-selectin or ICAM-1/GAPDH). Renal IL-6 mRNA expression was 2.49 [SE 0.67] in saline-, 1.08 [SE 0.46] in Nyk- (p-value: 0.07), and 1.84 [SE 0.39] in GGA-treated groups (p-value: 0.81) measured in fold induction (IL-6/GAPDH).

These results suggest that Nyk reduces pro-inflammation during the brain death period, despite the unchanged expression of Hsp72. We think that the dosis of Nyk was too low to increase Hsp72 expression in all treated rats. To further explore the effects of Nyk on HSP expression, we want to assess the degree of apoptosis and the expression of other stress-induced HSP: Hsp90, HO-1.