Pretransplant urine cytokine pattern predicts acute kidney rejection

Abstract

Acute rejection (AR) remains a major problem after kidney transplantation and crucial determinant of long-term graft function. Potent mediators of alloimmune response leading to AR are cytokines. To further explore the relation between cytokine pattern and frequency of AR episodes we analyzed Th1/Th2 cytokine concentrations in the urine of 44 patients prior to the kidney transplantation. During the 6-month period following the transplantation AR was diagnosed in 11 patients. Urine samples were collected 1day before the transplantation. Samples were cytometrically tested for concentrations of IL-2, IL-4, IL-5, IL-10, IFN-gamma and TNF-alpha. Analysis showed significantly higher pretransplant concentrations of IFN-gamma (P > .001), TNF-alpha (P < .05) and IL-10 (P < .001) in the urine of patients with diagnosed AR. No significant differences in the concentrations of IL-2, IL-4, IL-5 between the two groups were observed. Elevated pretransplant concentrations of urine IFN-gamma and TNF-alpha in AR patients, not accompanied by higher concentrations of IL-2, may suggest an ongoing undetected and local, non-specific Th1 immune response, capable of amplifying the alloimmune response in the early phase postsurgery. While higher concentrations of IL-10 can partially result from activation of monocytes/macrophages, and partially from peripheral regulatory mechanisms controlling the ongoing immune reaction.