Fumarate in the Preservation Solution Aggravates Chronic Allograft Nephropathy

Data on a protective role of fumarate in acute ischemia of the rat heart led to the obvious hypothesis that addition of fumarate to the preservation solution for kidney transplantation may have beneficial value. This study was designed to test this hypothesis. Kidneys of Lewis or Fischer 344 rats were flushed with University of Wisconsin (UW) solution or UW solution containing 5 mM fumarate. Grafts were immediately transplanted to Lewis recipients or stored at 4°C for 5 h before transplantation. Renal function was assessed on d 10 and monthly for 6 mo. One group of isografts was removed on d 10 post-transplantation, the other groups of isografts and allografts after 6 mo. We detected a modest protective effect regarding proteinuria 10 d after isogeneic transplantation, and exclude the possibility that fumarate exerts acute nephrotoxicity. Surprisingly, fumarate strongly promoted intimal hyperplasia of allograft arteries, thickening of the arterial media of isografts and allografts, tubulo-interstitial allograft damage, and allograft infiltration by macrophages on the long run. To date, we do not know the mechanism resulting in fumarate-induced chronic graft damage. We suggest, however, that addition of fumarate to the conservation fluid does not improve graft outcome.