Elevated Urinary CXCL10-to-Creatinine Ratio Is Associated With Subclinical and Clinical Rejection in Pediatric Renal Transplantation

Abstract

This study demonstrates that urinary CXCL10:Cr corresponds with microvascular inflammation and is a sensitive and specific biomarker for subclinical and clinical TCMR in children. This may provide a noninvasive monitoring tool for posttransplant immune surveillance for pediatric renal transplant recipients.

Urinary biomarkers of renal transplant outcome

“…This work builds on previous data that demonstrate urinary CXCR3 chemokines (CXCL9, CXCL10) are sensitive, noninvasive markers of subclinical and clinical TCMR [27,[49][50][51][52][53][54][55][56][57][58][59] and validates it in a large, unselected multicentre cohort [48]. Notably, in a prospective, observational single centre study Matz et al described that elevated urinary CXCL10 within the first month posttransplant was associated with GFR <45 ml/min at 6 months (AUC 0.68).…”

Early Low Urinary CXCL9 and CXCL10 Might Predict Immunological Quiescence in Clinically and Histologically Stable Kidney Recipients

“…2 The 95% confidence intervals were generated by 10 000 stratified bootstrap replicates. 3 In this context evaluating the performance of a given biomarker for predicting subsequent events, the sensitivity represents the proportion of at-risk patients among those who developed AR up to 400 days posttransplantation, and the specificity is the proportion of risk-free patients among those who did not develop AR up to 400 days posttransplantation.…”

“…2 Chronic histologic score defined by ci + ct + cv + ah + cg + mm Banff scores. 3 Including subclinical and clinical rejection episodes. 4 The urinary chemokine burden was calculated as the arithmetic mean of all of the available quantifications during the first 3 months.…”

“…Urinary chemokines, mainly the CXCR3-binding chemokines known as chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10, are secreted by infiltrating inflammatory cells and renal tubular and endothelial cells (2) and have been thoroughly investigated as noninvasive biomarkers of acute rejection (AR) (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Many observational crosssectional studies performed at the time of indication biopsies have clearly demonstrated their diagnostic performance in the setting of acute T cell-mediated rejection (TCMR) of renal allografts (5,6,8,12,13), and we recently reported that the urine level of CXCL10 at the time of an indication biopsy is also strongly indicative of antibody-mediated rejection (ABMR) (11).…”

Chemokines and transplant outcome

“…Furthermore, post-transplant CXCL10 detected as transcript in urinary cells predicts kidney acute rejection with a cut-off value of 9.11 mRNA [89], while high CXCL10 plasma level measured after lung transplantation associated with grade 3 graft dysfunction [90]. Urinary CXCL10 and CXCL9 tested in pediatric (CTOT in Children 3U01AI077821-02S1) and adult kidney recipients are able to detect rejection earlier than traditionally monitoring with serum creatinine, thus retaining high potentiality to improve long-term outcome and life quality [91,92]. Furthermore, serum and intrahepatic CXCL10 has been associated with higher necroinflammation and fibrosis in patients after liver transplantation for hepatitis C [93,94]; remarkably, CXCL10 emerged to be the only independent parameter associated with fibrosis progression post-transplantation.…”