In vivo prostanoid formation during acute renal allograft rejection.
Vasoconstriction during acute renal allograft rejection may be regulated by increased formation of vasoactive prostanoids. To address this hypothesis we investigated the biosynthesis of thromboxane (Tx)A2, a potent vasoconstrictor and platelet agonist, of prostacyclin (PGI2), a vasodilator and platelet antagonist, and of prostaglandin (PG)E2, a mediator of salt and water excretion, in nine children with 12 acute rejection episodes, prospectively during the first 7 weeks after renal transplantation. We used physicochemical analysis of stable urinary prostanoid index metabolites. Rejection crises were associated with an increase in TxB2 excretion from baseline median 9.2 (range 1.9-18.6) ng/h/1.73 m2 to 21.2 (range 10.0-133.0) ng/h/1.73 m2 (P < 0.005) during acute rejection episodes. Methylprednisolone pulse therapy resulted in a partial reduction, but not normalization of TxB2 excretion. Urinary 2,3-dinor-TxB2 was slightly stimulated during allograft rejection, urinary 11-dehydro-TxB2 did not change significantly. Renal PGI2 and PGE2 biosynthesis remained essentially unchanged. In contrast to acute graft rejection, patients with chronic graft rejection and those with stable graft function on different immunosuppressive regimens with or without cyclosporin A did not present stimulated renal TxA2 formation. Increased renal TxA2 formation in acute renal allograft rejection is likely to mediate vasoconstriction and potentiate the loss of renal blood flow and glomerular filtration rate, in the absence of an adequate response of the renoprotective prostanoids PGI2 and PGE2.
Tönshoff
B
B
Division of Pediatric Nephrology, University Children's Hospital, Heidelberg, Germany.
Busch
C
C
Schweer
H
H
Schärer
K
K
Seyberth
H W
HW
D000208:Acute Disease; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000493:pharmacokinetics; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000096:biosynthesis*; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000652:urine; D014184:Transplantation, Homologous
D011453:Prostaglandins; D013929:Thromboxane B2; D013928:Thromboxane A2; D016572:Cyclosporine; D003404:Creatinine