Randomized Trial to Assess the Clinical Utility of Renal Allograft Monitoring by Urine CXCL10 Chemokine

Abstract

Significance Statement This study is the first randomized controlled trial to investigate the clinical utility of a noninvasive monitoring biomarker in renal transplantation. Although urine CXCL10 monitoring could not demonstrate a beneficial effect on 1-year outcomes, the study is a rich source for future design of trials aiming to explore the clinical utility of noninvasive biomarkers. In addition, the study supports the use of urine CXCL10 to assess the inflammatory status of the renal allograft. Background Urine CXCL10 is a promising noninvasive biomarker for detection of renal allograft rejection. The aim of this study was to investigate the clinical utility of renal allograft monitoring by urine CXCL10 in a randomized trial. Methods We stratified 241 patients, 120 into an intervention and 121 into a control arm. In both arms, urine CXCL10 levels were monitored at three specific time points (1, 3, and 6 months post-transplant). In the intervention arm, elevated values triggered performance of an allograft biopsy with therapeutic adaptations according to the result. In the control arm, urine CXCL10 was measured, but the results concealed. The primary outcome was a combined end point at 1-year post-transplant (death-censored graft loss, clinical rejection between month 1 and 1-year, acute rejection in 1-year surveillance biopsy, chronic active T-cell–mediated rejection in 1-year surveillance biopsy, development of de novo donor-specific HLA antibodies, or eGFR <25 ml/min). Results The incidence of the primary outcome was not different between the intervention and the control arm (51% versus 49%; relative risk (RR), 1.04 [95% confidence interval, 0.81 to 1.34]; P = 0.80). When including 175 of 241 (73%) patients in a per-protocol analysis, the incidence of the primary outcome was also not different (55% versus 49%; RR, 1.11 [95% confidence interval, 0.84 to 1.47]; P = 0.54). The incidence of the individual end points was not different as well. Conclusions This study could not demonstrate a beneficial effect of urine CXCL10 monitoring on 1-year outcomes (ClinicalTrials.gov_NCT03140514).

Urine CXCL10 to Assess BK Polyomavirus Replication After Kidney Transplantation

“…Additionally, urine CXCL10 levels ≤3 ng/mmol were observed in about 50% of samples collected between 1 and 6 mo posttransplant and are associated with a low risk for rejection. 18 Taken together, low urine CXCL10 defines patients with a low risk for rejection and BKPyV replication. Therefore, urine CXCL10 could serve as a combined first-line monitoring test for the exclusion of 2 very important allograft pathologies.…”

“…This is a secondary analysis of the interventional, randomized trial investigating the clinical utility of urine CXCL10 for renal allograft monitoring in 241 patients. 18 The study was approved by the local ethics committee (EKNZ 2017-00742). Urine samples for CXCL10 analyses were collected at weeks 4, 5, 10, 11, 22, and 24, as well as at 1 y.…”

“…We recently completed a randomized controlled trial investigating the clinical utility of urine CXCL10 for renal allograft monitoring. 18 This cohort includes urine samples that were collected at specific screening time points allowing us to explore the diagnostic characteristics of urine CXCL10 for the detection of BKPyV replication. Additionally, it allowed us to validate the conflicting results obtained by Weseslindtner and Tinel regarding the correlation of urine CXCL10 and BKPyV infection stages.…”

Authors' Reply: Of End Points and Context of Use: A Reasonable Silver Lining for Urinary Chemokines Monitoring

“…We highly appreciate the thoughtful comments of Pagliazzi et al 1 They raise three very important questions, which we only touched on partially in the discussion of our publication. 2 Biomarker-driven management is a complex process involving a combined diagnostic and therapeutic concept. The therapeutic intervention on detection of subclinical rejection in the intervention arm was not strictly standardized, as Pagliazzi et al correctly point out.…”

“…We highly appreciate the thoughtful comments of Pagliazzi et al 1 They raise three very important questions, which we only touched on partially in the discussion of our publication. 2…”