Optimizing the approach to monitoring allograft inflammation using serial urinary CXCL10/creatinine testing in pediatric kidney transplant recipients

Abstract

BackgroundUrinary CXCL10/creatinine (uCXCL10/Cr) is proposed as an effective biomarker of subclinical rejection in pediatric kidney transplant recipients. This study objective was to model implementation in the clinical setting.MethodsBanked urine samples at a single center were tested for uCXCL10/Cr to validate published thresholds for rejection diagnosis (>80% specificity). The positive predictive value (PPV) for rejection diagnosis for uCXCL10/Cr‐indicated biopsy was modeled with first‐positive versus two‐test‐positive approaches, with accounting for changes associated with urinary tract infection (UTI), BK and CMV viremia, and subsequent recovery.ResultsSeventy patients aged 10.5 ± 5.6 years at transplant (60% male) had n = 726 urine samples with n = 236 associated biopsies (no rejection = 167, borderline = 51, and Banff 1A = 18). A threshold of 12 ng/mmol was validated for Banff 1A versus no‐rejection diagnosis (AUC = 0.74, 95% CI = 0.57–0.92). The first‐positive test approach (n = 69) did not resolve a clinical diagnosis in 38 cases (55%), whereas the two‐test approach resolved a clinical diagnosis in the majority as BK (n = 17/60, 28%), CMV (n = 4/60, 7%), UTI (n = 8/60, 13%), clinical rejection (n = 5/60, 8%), and transient elevation (n = 18, 30%). In those without a resolved clinical diagnosis, PPV from biopsy for subclinical rejection is 24% and 71% (p = .017), for first‐test versus two‐test models, respectively. After rejection treatment, uCXCL10/Cr level changes were all concordant with change in it‐score. Sustained uCXCL10/Cr after CMV and BK viremia resolution was associated with later acute rejection.ConclusionsUrinary CXCL10/Cr reliably identifies kidney allograft inflammation. These data support a two‐test approach to reliably exclude other clinically identifiable sources of inflammation, for kidney biopsy indication to rule out subclinical rejection.