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.

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 November 22, 2024.

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