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

摘要

Objective: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 a potential candidate to reflect ongoing immune processes within the renal graft.Methods:We investigated urinary CXCL13 levels by a cross-sectional analysis of 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 with acute tubular necrosis (ATN,P=0.001),chronic allograft nephropathy (CAN,P=0.01) and acute 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 further distinguished 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 month was predictive of graft function at 3,6 months,P=0.044 and 0.4.Conclusion:This study demonstrates 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.