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Observational Study
. 2021 Apr;21(4):1545-1555.
doi: 10.1111/ajt.16336. Epub 2020 Oct 30.

Validity and utility of urinary CXCL10/Cr immune monitoring in pediatric kidney transplant recipients

Tom D Blydt-Hansen  1 , Atul Sharma  2 , Ian W Gibson  3 , Chris Wiebe  4   5 , Ajay P Sharma  6 , Valerie Langlois  7 , Chia W Teoh  7 , David Rush  4 , Peter Nickerson  4   5 , David Wishart  8   9 , Julie Ho  4   10
Affiliations
Free article
Observational Study

Validity and utility of urinary CXCL10/Cr immune monitoring in pediatric kidney transplant recipients

Tom D Blydt-Hansen et al. Am J Transplant. 2021 Apr.
Free article

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.

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References

REFERENCES

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