Deciphering the Prognostic and Predictive Value of Urinary CXCL10 in Kidney Recipients With BK Virus Reactivation.

Claire Tinel,Anne Scemla,Fabiola Terzi,Xavier Lebreton,Dany Anglicheau,Marc Olivier Timsit,Lise Morin,Daniela Picciotto,Séverine Brabant,Laïla Aouni,Agathe Vermorel,Marion Rabant,Arnaud Devresse,Véronique Avettand-Fenoel,Virginia Sauvaget,Renaud Snanoudj,Dominique Prié,Christophe Legendre

doi:10.3389/fimmu.2020.604353

Abstract

BK virus (BKV) replication increases urinary chemokine C-X-C motif ligand 10 (uCXCL10) levels in kidney transplant recipients (KTRs). Here, we investigated uCXCL10 levels across different stages of BKV replication as a prognostic and predictive marker for functional decline in KTRs after BKV-DNAemia. uCXCL10 was assessed in a cross-sectional study (474 paired urine/blood/biopsy samples and a longitudinal study (1,184 samples from 60 KTRs with BKV-DNAemia). uCXCL10 levels gradually increased with urine (P-value < 0.0001) and blood BKV viral load (P < 0.05) but were similar in the viruria and no BKV groups (P > 0.99). In viremic patients, uCXCL10 at biopsy was associated with graft functional decline [HR = 1.65, 95% CI (1.08–2.51), P = 0.02], irrespective of baseline eGFR, blood viral load, or BKVN diagnosis. uCXL10/cr (threshold: 12.86 ng/mmol) discriminated patients with a low risk of graft function decline from high-risk patients (P = 0.01). In the longitudinal study, the uCXCL10 and BKV-DNAemia trajectories were superimposable. Stratification using the same uCXCL10/cr threshold at first viremia predicted the subsequent inflammatory response, assessed by time-adjusted uCXCL10/cr AUC (P < 0.001), and graft functional decline (P = 0.03). In KTRs, uCXCL10 increases in BKV-DNAemia but not in isolated viruria. uCXCL10/cr is a prognostic biomarker of eGFR decrease, and a 12.86 ng/ml threshold predicts higher inflammatory burdens and poor renal outcomes.

Highlights

Almost 50 years after its first description in kidney transplant recipients (KTRs) [1], BK polyomavirus (BKV) remains a clinical concern, with BKV-DNAemia still found in 10–30% of KTRs, leading to BKV-associated nephropathy (BKVN) in 1–10% [2]
BKV-DNAemia was detectable in 16% of cases, with a median viral load of 3.32 [interquartile range (IQR): 3.1] Log10 copies/ml, and 5.3% met the criteria for BKVN (N = 25)
chemokine CX-C motif ligand 10 (CXCL10) groups are defined according to uCXCL10/cr at first DNAemia: ≤12.86 ng/mmol or >12.86 ng/mmol

Summary

Introduction

Almost 50 years after its first description in kidney transplant recipients (KTRs) [1], BK polyomavirus (BKV) remains a clinical concern, with BKV-DNAemia still found in 10–30% of KTRs, leading to BKV-associated nephropathy (BKVN) in 1–10% [2]. Upon development as a biomarker for the noninvasive diagnosis of allograft rejection [5,6,7,8,9], increased levels of urinary chemokines have repeatedly been reported in patients with BKV infection [8, 10,11,12,13,14]. It has been regarded as a confounding factor to date, we aimed to investigate urinary CX-C motif chemokine 10 (uCXCL10) as a diagnostic biomarker in the course of BKV infection by determining uCXCL10 levels across different stages of BKV replication, evaluating its potential as a prognostic biomarker in comparison to conventional biological and histological markers, and describing the longitudinal course of uCXCL10 in BKV infection

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Conclusion