Increased intracellular adenosine triphosphate level as an index to predict acute rejection in kidney transplant recipients

Background: Peripheral blood CD4 + T cell adenosine triphosphate (ATP) release has been reported to be an adjunct tool to evaluate global cellular immune response in solid-organ transplant recipients. However, the correlation between the ATP level and rejection was controversial. The aim of this prospective clinical study was to explore the association between the intracellular ATP level and the occurrence, progression, and treatment of acute rejection (AR) episodes, determine the predicting value of intracellular ATP level for AR in kidney transplant (KT) recipients. Patients and methods: In the period of October 2011 to October 2012, 140 KT recipients were recruited and followed for six months after transplantation. Patients were categorized into stable group and AR group according to their clinical course. Whole blood samples were collected pretransplantation, and at 7, 14, 21, and 28 days, and at 2, 3, 4, 5 and 6 months post-transplantation. Additional blood samples were obtained from AR patients on the day AR occurred, on the day before and 3 and 7 days after intravenous anti-rejection therapy started, and on the day when AR reversed. The intracellular ATP in CD4 + T cells was detected by ImmuKnow Immune Cell Function Assay according to the manufacturer's instruction. The absolute number of CD4 + T cells and the trough levels of tacrolimus and cyclosporine were also measured. Results: The ATP level detected on the day AR occurred (627.07 ± 149.85 ng/ml) was obviously higher than that of the stable group (320.48 ± 149.11 ng/ml, P < 0.05). ATP value decreased to 265.35 ± 84.33 ng/m at the end of anti-rejection therapy, which was obviously lower than that measured on the day before the anti-rejection therapy started (665.87 ± 162.85 ng/ml, P < 0.05). ROC analysis revealed that increased intracellular adenosine triphosphate level showed better sensitivity and specificity than those obtained using single time point detection (89.5% vs 85.0%;95.0% vs 88.9%). The best cutoff value was 172.55 ng/ml. A positive correlation between the intracellular ATP level and absolute CD4 + T cell number (r = 0.656, P < 0.001) was found in the patients with CD4 + T cell counts < 200/μl.