Immunologic rejection is the leading cause of failure of renal transplantation. The objective of the proposed program will be to develop an assay for monitoring kidney transplant recipients for the onset of graft rejection and to help distinguish graft rejection from other renal and extrarenal problems in these patients. Since immunologic attack on the renal tubules is the primary cause of rejection, an assay that measures the response of the renal tubules to these immunologic events could be especially useful. The expression of the epithelial glycoprotein, secretory component is enhanced by some inflammatory cytokines. We therefore propose that an assay for the free form of secretory component (FSC) in the urine, may be a sensitive indicator of kidney transplant rejection. The proposed approach for this phase I project will be to transfer the assay for urinary FSC from the research laboratory to our company's laboratory. We will then optimize the procedure for commercial application. Once optimized, the assay will be validated by comparing it with the research assay. The precision, sensitivity, specificity and cross-reactivity of the commercial assay will then be determined. The new assay will also be used to determine the best sampling method for estimating the excretory rate for urinary FSC, determining the stability of FSC in clinical samples and defining therapeutic variables that might confound the association between kidney transplant rejection and increased urinary FSC excretion.
