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
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2021 AprIndividualized 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. © 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.
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. Validity and utility of urinary CXCL10/Cr immune monitoring in pediatric kidney transplant recipients. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2021 Apr;21(4):1545-1555
PMID: 33034126
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