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Validity and utility of urinary CXCL10/Cr immune monitoring in pediatric kidney transplant recipients |
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| Authors: | Tom D. Blydt-Hansen Atul Sharma Ian W. Gibson Chris Wiebe Ajay P. Sharma Valerie Langlois Chia W. Teoh David Rush Peter Nickerson David Wishart Julie Ho |
| Affiliation: | 1. Pediatric Nephrology, The University of British Columbia, Vancouver, British Columbia, Canada;2. Biostatistical Consulting Unit, George, Fay Yee Center for Healthcare Innovation, University of Manitoba, Winnipeg, Manitoba, Canada;3. Pathology, University of Manitoba, Winnipeg, Manitoba, Canada;4. Nephrology, University of Manitoba, Winnipeg, Manitoba, Canada;5. Pediatric Nephrology, University of Western Ontario, London, Ontario, Canada;6. Pediatric Nephrology, University of Toronto, Toronto, Ontario, Canada;7. Computing Science, University of Alberta, Edmonton, Alberta, Canada The Metabolomics Innovation Center, Edmonton, Alberta, Canada;8. Nephrology, University of Manitoba, Winnipeg, Manitoba, Canada Manitoba Centre for Proteomics & Systems Biology, Winnipeg, Manitoba, Canada |
| Abstract: | Individualized posttransplant immunosuppression is hampered by suboptimal monitoring strategies. To validate the utility of urinary CXCL10/Cr immune monitoring in children, we conducted a multicenter prospective observational study in children <21 years with serial and biopsy-associated urine samples (n = 97). Biopsies (n = 240) were categorized as normal (NOR), rejection (>i1t1; REJ), indeterminate (IND), BKV infection, and leukocyturia (LEU). An independent pediatric cohort of 180 urines was used for external validation. Ninety-seven patients aged 11.4 ± 5.5 years showed elevated urinary CXCL10/Cr in REJ (3.1, IQR 1.1, 16.4; P < .001) and BKV nephropathy (median = 5.6, IQR 1.3, 26.9; P < .001) vs. NOR (0.8, IQR 0.4, 1.5). The AUC for REJ vs. NOR was 0.76 (95% CI 0.66–0.86). Low (0.63) and high (4.08) CXCL10/Cr levels defined high sensitivity and specificity thresholds, respectively; validated against an independent sample set (AUC = 0.76, 95% CI 0.66–0.86). Serial urines anticipated REJ up to 4 weeks prior to biopsy and declined within 1 month following treatment. Elevated mean CXCL10/Cr was correlated with first-year eGFR decline (ρ = −0.37, P ≤ .001), particularly when persistently exceeding ≥4.08 (ratio = 0.81; P < .04). Useful thresholds for urinary CXCL10/Cr levels reproducibly define the risk of rejection, immune quiescence, and decline in allograft function for use in real-time clinical monitoring in children. |
| Keywords: | biomarker biopsy chemokines/chemokine receptors clinical research/practice kidney (allograft) function/dysfunction kidney transplantation/nephrology pediatrics rejection: acute |