Increasing urinary IL-6 levels announce kidney graft rejection

Abstract

Acute rejection (AR) is the recipient's inflammatory response to the grafted organ. Within the graft-infiltrating cells, a high ratio of IL-6 producing cells can be found, indicating local IL-6 production. Therefore, in cases of kidney transplantation, urinary (u) IL-6 should be detectable. In order to establish the dynamics and diagnostic relevance, uIL-6 levels were determined daily by Quantikine IL-6 immunoassay (R & D Systems, Minneapolis, Minn.) in 101 kidney graft recipients (n = 1915 urine samples) during their post-transplant hospital stay. Immunosuppression consisted of azathioprine, steroids, cyclosporine and an intraoperative high-dose single antithymocyte globulin (ATG)-Fresenius bolus (9 mg/kg). In all the uncomplicated courses (n = 31) mean uIL-6 level was determined, after a post-transplant peak of 174 pg/ml, to be between 4 and 8 pg/ml. In contrast, delayed graft function (n = 16) was always associated with very high uIL-6 levels (> 200 pg/ml), dropping down only with commencement of graft function. Steroid-sensitive AR (n = 14) was consistently associated with significantly increasing uIL-6 levels prior to antirejection therapy (from 23 to 82 pg/ml). In cases of steroid-resistant AR, following antirejection therapy with methylprednisolone (5 days 5 mg/kg), there was no obvious trend towards normalization, indicating the persistence of inflammation (mean uIL-6 peak prior to OKT3 or ATG therapy: 99 pg/ml). In addition, AR-associated uIL-6 levels were found to be of much greater diagnostic relevance than AR-associated serum IL-6 levels. In bacterial urinary tract infections (n = 20), increased uIL-6 levels (peak 53 pg/ml) coincided with the commencement of antibiotic therapy. In mild cytomegalovirus diseases (n = 8), the development of leukocytopenia was associated with a slight increase of uIL-6 (peak 26 pg/ml), showing graft involvement. All increased uIL-6 values returned towards baseline after successful treatment. Thus, uIL-6 provides information about the intragraft inflammatory situation. Its determination is simple, expressive, non-invasive and can be recommended.