High CXCL10 expression in rejected kidneys and predictive role of pretransplant serum CXCL10 for acute rejection and chronic allograft nephropathy.

Background: Several experimental models have shown that CXCL10 is required for initiation and development of graft failure caused by both acute and chronic rejection. Methods: CXCL10 expression and distribution was investigated in tissue specimens obtained from 22 patients suffering from acute rejection (AR) or chronic allograft nephropathy (CAN) by using in situ hybridization. Furthermore, pretransplantation sera of 316 cadaveric kidney-graft recipients were tested retrospectively for serum CXCL10 levels by a quantitative sandwich immunoassay. Results: Bioptic specimens obtained from patients with CAN were characterized by wide CXCL10 expression not only at level of infiltrating inflammatory cells but also of vascular, tubular, and glomerular structures. In addition, assessment of pretransplant serum CXCL10 levels in 316 graft recipients and stratification of patients in three groups according to serum CXCL10 levels (<100 pg/mL, n=163; 100-150 pg/mL, n=69; >150 pg/mL, n=84) showed highly significant differences in 5-year survival rates for the two extreme groups (95.7% vs. 79.7%, P=0.0002). Accordingly, patients who developed severe, early AR (277.14+/-65.08 p=0.004) and those who developed CAN also showed increased pretransplant serum CXCL10 levels (193.2+/-36.9, P=0.03). Multivariate analysis demonstrated that among the analyzed variables, CXCL10 (relative risk [RR] 2.801) and delayed graft function (RR 3.728) had the highest predictive power of graft loss. Conclusions: These results suggest that pretransplant serum CXCL10 levels greater than 150 pg/mL confer an increased risk of early, severe, AR and subsequent CAN, finally resulting in renal-allograft failure. This finding might be used for the individualization of immunosuppressive therapies.