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.

Abstract

Increasing evidence exists that inducible adhesion molecules are involved in cell-mediated allograft rejection. In addition, complement activation during rejection has been described. This study investigated, whether specific molecules derived from either pathway are excreted into urine during rejection and whether they can provide useful diagnostic tools for the monitoring of renal transplant recipients. Urinary concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1, sE-selectin) and of complement cleavage products (sC4d and sC5b-9), were determined by standardized ELISA in 30 normal controls and 80 samples from 49 recipients of renal allografts. In contrast to the low amounts of adhesion molecules and complement components uniformly excreted by healthy persons (group 0), marked differences were observed among allograft recipients. To prove the clinical relevance of these differences in excretion, patient samples were assigned to 5 categories according to clinical and histopathological criteria: group I--acute steroid-resistant 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, sVCAM-1, and sC4d were significantly higher in group I compared with all other groups (P < 0.01). The difference in sICAM-1 excretion between groups III and IV also reached statistical significance (P < 0.05). Urinary concentrations of sICAM-1, sVCAM-1, and sC4d were reflective of their histological distribution in corresponding graft biopsies. None of the patients excreted E-selectin in detectable amounts. Excretion of the terminal membrane attack complex C5b-9 was not significantly associated 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 type of allograft rejection.