ASSESSMENT OF SOLUBLE ADHESION MOLECULES (SICAM-1, SVCAM-1, SELAM-1) AND COMPLEMENT CLEAVAGE PRODUCTS (SC4D, SC5B-9) IN URINE - CLINICAL MONITORING OF RENAL-ALLOGRAFT RECIPIENTS

Increasing evidence exists that inducible adhesion molecules are invol ved in cell-mediated allograft rejection. In addition, complement acti vation during rejection has been described. This study investigated, w hether specific molecules derived from either pathway are excreted int o urine during rejection and whether they can provide useful diagnosti c tools for the monitoring of renal transplant recipients. Urinary con centrations of soluble adhesion molecules (sICAM-1, sVCAM-1, sE-select in) and of complement cleavage products (sC4d and sC5b-9), were determ ined by standardized ELISA in 30 normal controls and 80 samples from 4 9 recipients of renal allografts. In contrast to the low amounts of ad hesion molecules and complement components uniformly excreted by healt hy persons (group 0), marked differences were observed among allograft recipients. To prove the clinical relevance of these differences in e xcretion, patient samples were assigned to 5 categories according to c linical and histopathological criteria: group I-acute steroid-resistan t rejection (n=10); group II-acute steroid-sensitive rejection (n=10); group III-chronic rejection (n=23); group IV-stable graft function (n =27); and group V-miscellaneous disorders (n=10), including infections , CsA overdoses, and glomerulonephritis. Urinary levels of sICAM-1, sV CAM-1, and sC4d were significantly higher in group I compared with all other groups (P<0.01). The difference in sICAM-1 excretion between gr oups III and IV also reached statistical significance (P<0.05). Urinar y concentrations of sICAM-1, sVCAM-1, and sC4d were reflective of thei r histological distribution in corresponding graft biopsies. None of t he patients excreted E-selectin in detectable amounts. Excretion of th e terminal membrane attack complex C5b-9 was not significantly associa ted with any diagnosis. It is concluded that for clinical purposes the combined evaluation of sICAM-1, sVCAM-1, and sC4d is most useful and can provide valuable information with regard to the severity and the t ype of allograft rejection.