In vivo prostanoid formation during acute renal allograft rejection

Vasoconstriction during acute renal allograft rejection maybe regulated by increased formation of vasoactive prostanoids.To address this hypothesis we investigated the biosynthesisof thromboxane (Tx)A₂, a potent vasoconstrictor and plateletagonist, of prosta-cyclin (PGI₂), a vasodilator and plateletantagonist, and of prostaglandin (PG)E₂, a mediator of saltand water excretion, in nine children with 12 acute rejectionepisodes, prospectively during the first 7 weeks after renaltransplantation. We used physicochemical analysis of stableurinary prostanoid index metabolites. Rejection crises wereassociated with an increase in TxB₂ excretion from baselinemedian 9.2 (range 1.9–18.6) ng/h/1.73m² to 21.2 (range10.0–133.0) ng/h/1.73m² (P<0.005) during acute rejectionepisodes. Methylprednisolone pulse therapy resulted in a partialreduction, but not normalization of TxB₂ excretion. Urinary2,3-dinor-TxB₂ was slightly stimulated during allograft rejection,urinary 1 l-dehydro-TxB₂ did not change significantly. RenalPGI₂ and PGE₂ biosynthesis remained essentially unchanged. Incontrast to acute graft rejection, patients with chronic graftrejection and those with stable graft function on differentimmunosuppressive regimens with or without cyclosporin A didnot present stimulated renal TxA₂ formation. Increased renalTxA₂ formation in acute renal allograft rejection is likelyto mediate vasoconstriction and potentiate the loss of renalblood flow and glomerular filtration rate, in the absence ofan adequate response of the renoprotective prostanoids PGI₂and PGE₂.