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Validity and Utility of Urinary CXCL10/Cr Monitoring in Pediatric Kidney Transplant Recipients

T. Blydt-Hansen1, A. Sharma2, I. Gibson2, C. Weibe2, A. Sharma3, V. Langlois4, C. Teoh4, D. Rush2, P. Nickerson2, D. Wishart5, J. Ho2

1University of British Columbia, Vancouver, BC, Canada, 2University of Manitoba, Winnipeg, MB, Canada, 3University of Western Ontaria, London, ON, Canada, 4University of Toronto, Toronto, ON, Canada, 5University of Alberta, Edmonton, AB, Canada

Meeting: 2020 American Transplant Congress

Abstract number: A-311

Keywords: Monitoring, Outcome, Pediatric, Rejection

Session Information

Session Name: Poster Session A: Biomarkers, Immune Assessment and Clinical Outcomes

Session Type: Poster Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:00pm

 Presentation Time: 3:30pm-4:00pm

Location: Virtual

*Purpose: Effective post-transplant monitoring is hampered by a lack of effective biomarkers. We sought to validate the utility of urinary CXCL10/Cr monitoring of rejection in children.

*Methods: A multi-center, prospective, cohort study enrolled children <21 years old peri-transplant. Urine samples were collected at timed intervals and with biopsy, and analyzed for CXCL10 and creatinine (Cr). Biopsies were graded as no rejection (NOR), rejection (>i1,t1; REJ), indeterminate (>NOR, *Results: 97 patients with mean age 11.4 ± 5.5 years provided 1013 urine samples. 240 biopsy samples (REJ=41, NOR=84, BKV=21, LEU=24) were for surveillance (52%), indication (23%) or follow-up (24%). Median urinary CXCL10/Cr was elevated in REJ (3.1, IQR 1.1, 16.4) vs. NOR (0.8, IQR 0.4, 1.5; p<0.001) or IND (1.0, IQR 0.4,2.8; p=0.004). The AUC for REJ vs. NOR was 0.76 (95% CI 0.66-0.86). Samples with BKV (median=5.6, IQR 1.3, 26.9) also show significantly higher CXCL10/Cr compared with NOR (p<0.001) and IND (p<0.001). Low (0.63) and high (4.08) CXCL10/Cr thresholds defined high sensitivity (>90%) and high specificity (>90%), respectively; and had similar validity against an external sample set (AUC=0.76, 95% CI 0.66-0.86, with comparable sensitivity and specificity from the two distinct diagnostic thresholds). Discrimination remained robust when IND+NOR were grouped vs. REJ (AUC=0.73, 95% CI 0.64-0.82). Serial monitoring anticipated REJ up to 4 weeks prior to biopsy (median=43.5, IQR 10.4, 78.4) vs. NOR (median=1.8, IQR 0.9, 3.0; p<0.001), and declined within 1 month following treatment (1.8, IQR 0.5, 3.8; p=0.018 vs. biopsy day). Mean CXCL10/Cr over the first post-transplant year was correlated with eGFR decline (ρ= -0.37, p=<0.001), with mean CXCL10/Cr ≥4.08 demonstrating significantly greater decline (median ratio=0.81) vs. mid-range (0.63-4.08, median ratio=0.93; p=0.04) or low (≤0.63; median ratio=0.96; p=0.005) mean urinary CXCL10/Cr.

*Conclusions: Urinary CXCL10/Cr levels reproducibly define a low threshold that may avoid surveillance biopsy (high sensitivity) and a high threshold to indicate biopsy (high specificity), and vary predictably prior to and following treatment of rejection. Persistent elevation of CXCL10/Cr identifies an increased risk for functional decline in the first post-transplant year.

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To cite this abstract in AMA style:

Blydt-Hansen T, Sharma A, Gibson I, Weibe C, Sharma A, Langlois V, Teoh C, Rush D, Nickerson P, Wishart D, Ho J. Validity and Utility of Urinary CXCL10/Cr Monitoring in Pediatric Kidney Transplant Recipients [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/validity-and-utility-of-urinary-cxcl10-cr-monitoring-in-pediatric-kidney-transplant-recipients/. Accessed May 11, 2025.

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