Urinary C-X-C Motif Chemokines 13 is a Noninvasive Biomarker of Antibody-Mediated Renal Allograft Rejection

Abstract

Background Since acute rejection remains one of the major complications which necessitate periodic surveillance, noninvasive diagnostic/prognostic methods are preferred by renal transplant recipients. Here we explored whether urinary C-X-C motif chemokines 13(CXCL13) could be apotential candidate to reflect ongoing immune processes within the renal graft. Methods We investigated urinary CXCL13 levels by a cross-sectional analysisof 146 renal allograft recipients and 40 healthy controls. Besides, a subset of patients (n = 57) were followed-up for kinetic monitoring of immune status. Results Urinary CXCL13/Cr was lower in normal transplants compared to those withacute tubular necrosis (ATN, P = 0.001), chronic allograft nephropathy (CAN, P = 0.01) andacute rejection (AR, P < 0.0001), which yielded a good diagnosis performance of urinary CXCL13 for AR (AUC = 0.818, P< 0.0001). Interestingly, urinary CXCL13 furtherdistinguished acute antibody mediated rejection (ABMR)from acute cellular rejection, with an AUC of 0.856. Besides,patients with steroid-resistant acute rejection had distinctly greater urinary CXCL13/Cr levels than patients with reversible acute rejection, P =0.001. Follow-up data revealed that urinary CXCL13/Cr varied in line with the occurrence of ABMR. Furthermore, elevated levels of urinary CXCL13/Cr within the first monthwas predictive of graft function at 3, 6 months, P=0.044 and 0.4. Conclusion This study demonstrated that monitoring of urinary CXCL13/Cr might be a valuable noninvasive approach for the detection of AR, especially ABMR. Additionally, high urinary CXCL13/Cr levels related to the poor response to steroid treatment and predicted a compromised graft function after AR. Key Words:C-X-C motif chemokines 13; kidney transplantation; rejection; urine Key Laboratory of Multiple Organ Transplantation, Ministry ofHealth.