THROMBOXANE SYNTHASE EXPRESSION IN RENAL-TRANSPLANT PATIENTS WITH REJECTION

Thromboxane synthase (TS) catalyzes the formation of thromboxane (TxA( 2)) in monocytes/macrophages, platelets, and various tissues. TxA(2) i s likely to play a role in graft dysfunction due to its vasoconstricti ve and platelet aggregatory properties. We studied the expression of T S in 7 normal native kidneys, 29 consecutive renal allograft biopsies (performed for rising serum creatinine, n=23, and delayed graft functi on, n=6), and one transplant nephrectomy specimen with severe acute re jection. TS expression was determined by immunocytochemistry using a m onoclonal antibody against human TS, Kon-7. Histologic grading of the transplant biopsy specimens was based on the Banff classification. The degree of TS staining was graded in the glomeruli, interstitium, tubu les and vessels from 0 to 3+. Of 29 biopsies, 13 had chronic nephropat hy (CN), 6 had acute rejection (AR) with chronic nephropathy (AR/CN), 4 had acute rejection (AR), and 6 had acute tubular necrosis (ATN). TS staining of native kidneys showed sporadic interstitial cells, The bi opsy and transplant nephrectomy specimens showed significant staining, predominantly in the glomeruli and interstitium. Positively staining cells appeared to be of macrophage/monocyte lineage by morphology. The mean glomerular staining grade was significantly increased in specime ns with AR (2.3+/-0.9) and the mean interstitial staining was increase d in specimens with AR/CN (2.2+/-0.9). Follow-up renal function 6 mont hs post-biopsy showed that patients with higher TS staining grades had a faster decline in graft function. In conclusion, TS expression is i ncreased in patients with acute rejection with or without chronic neph ropathy and is associated with more rapid deterioration in function.