title: Increased intracellular adenosine triphosphate level as an index to predict acute rejection in kidney transplant recipients.
abstract: 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.
  
  
  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 28days, and at 2, 3, 4, 5 and 6months post-transplantation. Additional blood samples were obtained from AR patients on the day AR occurred, on the day before and 3 and 7days 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±149.85ng/ml) was obviously higher than that of the stable group (320.48±149.11ng/ml, P<0.05). ATP value decreased to 265.35±84.33ng/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±162.85ng/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 172.55ng/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.
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Xu-Zhen
authors.initials: XZ
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Shaanxi Provincial People's Hospital (The Third Affiliated Hospital of Medical College of Xi'an Jiaotong University), Xi'an, Shaanxi, China.
authors.forename: Zhan-Kui
authors.initials: ZK
authors.lastname: Jin
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Tian
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address: xwujun@126.com.
authors.forename: Wu-Jun
authors.initials: WJ
authors.lastname: Xue
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Pu-Xun
authors.initials: PX
authors.lastname: Tian
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Ding
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jing
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Zi-Zhen
authors.initials: ZZ
authors.lastname: Luo
mesh_terms: D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002452:Cell Count; D016572:Cyclosporine / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D042541:Intracellular Space / Q000378:metabolism*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage; D014180:Transplantation
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D016559:Tacrolimus
keywords: Acute rejection; Adenosine triphosphate (ATP); Kidney transplantation