Transforming kidney transplant monitoring with urine CXCL9 and CXCL10: practical clinical implementation.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 Sep 2024
02 Sep 2024
Historique:
received:
24
06
2024
accepted:
16
08
2024
medline:
3
9
2024
pubmed:
3
9
2024
entrez:
2
9
2024
Statut:
epublish
Résumé
In kidney transplant recipients, urine CXCL9 and CXCL10 (uCXCL9/10) chemokines have reached a sufficiently high level of evidence to be recommended by the European Society of Organ Transplantation for the monitoring of immune quiescence. To assess the risk of acute rejection (AR), the advantage of uCXCL9/10 is their cost-effectiveness and their high diagnostic performance. Here, we evaluated the feasibility of a next-generation immunoassay for quantifying uCXCL9/10 levels. It demonstrated high efficiency with minimal workflow and a 90-min time to result. Preanalytical studies indicated stability of uCXCL9/10 levels and analytical studies confirmed excellent linearity and precision. In a cohort of 1048 samples collected at biopsy, the results correlated significantly with ELISA quantification and were integrated into a previously validated 8-parameter urine chemokine model. The next generation immunoassay achieved an accuracy of 0.84 for AR diagnosis. This study validates this technology as a robust, locally available and unexpensive platform and marks a significant step towards the widespread implementation of uCXCL9/10, for immune quiescence monitoring. Therefore, we developed an open-access web application using uCXCL9/10 to calculate AR risk and improve clinical decision-making to perform biopsy, ushering in a new era in kidney transplantation, where personalized, data-driven care becomes the norm.
Identifiants
pubmed: 39223175
doi: 10.1038/s41598-024-70390-x
pii: 10.1038/s41598-024-70390-x
doi:
Substances chimiques
Chemokine CXCL10
0
Chemokine CXCL9
0
CXCL9 protein, human
0
CXCL10 protein, human
0
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
20357Informations de copyright
© 2024. The Author(s).
Références
Naesens, M. & Anglicheau, D. Precision transplant medicine: Biomarkers to the rescue. J. Am. Soc. Nephrol. 29, 24–34 (2018).
doi: 10.1681/ASN.2017010004
pubmed: 28993504
Anglicheau, D., Naesens, M., Essig, M., Gwinner, W. & Marquet, P. Establishing biomarkers in transplant medicine: A critical review of current approaches. Transplantation 100, 2024–2038 (2016).
doi: 10.1097/TP.0000000000001321
pubmed: 27479159
Halloran, P. F. et al. Review: The transcripts associated with organ allograft rejection. Am. J. Transplant. 18, 785–795. https://doi.org/10.1111/ajt.14600 (2018).
doi: 10.1111/ajt.14600
pubmed: 29178397
Mas, V. R., Dumur, C. I., Scian, M. J., Gehrau, R. C. & Maluf, D. G. MicroRNAs as biomarkers in solid organ transplantation. Am. J. Transplant 13, 11–19 (2013).
doi: 10.1111/j.1600-6143.2012.04313.x
pubmed: 23136949
Bontha, S. V., Maluf, D. G., Mueller, T. F. & Mas, V. R. Systems biology in kidney transplantation: The application of multi-omics to a complex model. Am. J. Transplant. 17, 11–21 (2017).
doi: 10.1111/ajt.13881
pubmed: 27214826
Tinel, Claire et al. Modulation of monocyte response by microrna-15b/106a/374a during antibody-mediated rejection in kidney transplantation. Transplantation 107(5), 1089–1101. https://doi.org/10.1097/TP.0000000000004393 (2023).
doi: 10.1097/TP.0000000000004393
pubmed: 36398319
Tinel, C. et al. Integrative omics analysis unravels microvascular inflammation-related pathways in kidney allograft biopsies. Front. Immunol. 12, 738795 (2021).
doi: 10.3389/fimmu.2021.738795
pubmed: 34795664
pmcid: 8593247
Van Loon, E. et al. Biological pathways and comparison with biopsy signals and cellular origin of peripheral blood transcriptomic profiles during kidney allograft pathology. Kidney Int. https://doi.org/10.1016/j.kint.2022.03.026 (2022).
doi: 10.1016/j.kint.2022.03.026
pubmed: 35526671
pmcid: 9231008
Naesens, M., Friedewald, J., Mas, V., Kaplan, B. & Abecassis, M. M. A practical guide to the clinical implementation of biomarkers for subclinical rejection following kidney transplantation. Transplantation 104, 700–707. https://doi.org/10.1097/TP.0000000000003064 (2020).
doi: 10.1097/TP.0000000000003064
pubmed: 31815910
Mannon, R. B. Immune monitoring and biomarkers to predict chronic allograft dysfunction. Kidney Int. Suppl. 78, S59-65. https://doi.org/10.1038/ki.2010.425 (2010).
doi: 10.1038/ki.2010.425
Hu, H. et al. Elevation of CXCR3-binding chemokines in urine indicates acute renal-allograft dysfunction. Am. J. Transplant. https://doi.org/10.1111/j.1600-6143.2004.00354.x (2004).
doi: 10.1111/j.1600-6143.2004.00354.x
pubmed: 15476487
Jackson, J. A. et al. Urinary chemokines CXCL9 and CXCL10 are noninvasive markers of renal allograft rejection and BK viral infection. Am. J. Transplant. 11, 2228–2234 (2011).
doi: 10.1111/j.1600-6143.2011.03680.x
pubmed: 21812928
pmcid: 3184377
Hirt-Minkowski, P. et al. Detection of clinical and subclinical tubulo-interstitial inflammation by the urinary CXCL10 chemokine in a real-life setting. Am. J. Transplant. 12, 1811–1823 (2012).
doi: 10.1111/j.1600-6143.2012.03999.x
pubmed: 22390571
Suthanthiran, M. et al. Urinary-cell mRNA profile and acute cellular rejection in kidney allografts. N. Engl. J. Med. 369, 20–31 (2013).
doi: 10.1056/NEJMoa1215555
pubmed: 23822777
pmcid: 3786188
Rabant, M. et al. Urinary C-X-C motif chemokine 10 independently improves the noninvasive diagnosis of antibody-mediated kidney allograft rejection. J. Am. Soc. Nephrol. 26, 2840–51 (2015).
doi: 10.1681/ASN.2014080797
pubmed: 25948873
pmcid: 4625672
Sigdel, T. K. et al. A urinary common rejection module (uCRM) score for non-invasive kidney transplant monitoring. PLoS One 14, e0220052 (2019).
doi: 10.1371/journal.pone.0220052
pubmed: 31365568
pmcid: 6668802
Blydt-Hansen, T. D. et al. Validity and utility of urinary CXCL10/Cr immune monitoring in pediatric kidney transplant recipients. Am. J. Transplant. 21, 1545–1555 (2021).
doi: 10.1111/ajt.16336
pubmed: 33034126
Rabant, M. et al. Early low urinary CXCL9 and CXCL10 might predict immunological quiescence in clinically and histologically stable kidney recipients. Am. J. Transplant. 16, 1868–81 (2016).
doi: 10.1111/ajt.13677
pubmed: 26694099
Hricik, D. E. et al. Multicenter validation of urinary CXCL9 as a risk-stratifying biomarker for kidney transplant injury. Am. J. Transplant. 13, 2634–2644 (2013).
doi: 10.1111/ajt.12426
pubmed: 23968332
pmcid: 3959786
Ho, J. et al. Urinary CXCL10 chemokine is associated with alloimmune and virus compartment-specific renal allograft inflammation. Transplantation https://doi.org/10.1097/TP.0000000000001931 (2018).
doi: 10.1097/TP.0000000000001931
pubmed: 28902772
Tinel, C. et al. Development and validation of an optimized integrative model using urinary chemokines for noninvasive diagnosis of acute allograft rejection. Am. J. Transplant. https://doi.org/10.1111/ajt.15959 (2020).
doi: 10.1111/ajt.15959
pubmed: 32342614
Tinel, C. et al. Deciphering the prognostic and predictive value of urinary CXCL10 in kidney recipients with BK virus reactivation. Front. Immunol. 11, 604353 (2020).
doi: 10.3389/fimmu.2020.604353
pubmed: 33362789
pmcid: 7759001
Park, S. et al. European society of organ transplantation consensus statement on testing for non-invasive diagnosis of kidney allograft rejection. Transpl. Int. 36, 12115 (2023).
doi: 10.3389/ti.2023.12115
pubmed: 38239762
Sturgeon, C., Hill, R., Hortin, G. L. & Thompson, D. Taking a new biomarker into routine use–a perspective from the routine clinical biochemistry laboratory. Proteomics Clin. Appl. 4, 892–903 (2010).
doi: 10.1002/prca.201000073
pubmed: 21137030
pmcid: 3060337
Rabant, M. et al. Early low urinary CXCL9 and CXCL10 might predict immunological quiescence in clinically and histologically stable kidney recipients. Am. J. Transplant. 16, 1868–1881 (2016).
doi: 10.1111/ajt.13677
pubmed: 26694099
U.S. Food and Drug Administration. Bioanalytical Method Validation. Guidance for Industry. https://www.fda.gov/files/drugs/published/Bioanalytical-Method-Validation-Guidance-for-Industry.pdf (2018).
Van Loon, E. et al. Automated urinary chemokine assays for noninvasive detection of kidney transplant rejection: A prospective cohort study. Am. J. Kidney Dis. 83, 467–476 (2024).
doi: 10.1053/j.ajkd.2023.07.022
pubmed: 37777058
Park, S. et al. European society of organ transplantation consensus statement on testing for non-invasive diagnosis of kidney allograft rejection. Transplant. Int. https://doi.org/10.3389/ti.2023.12115 (2024).
doi: 10.3389/ti.2023.12115
Rabant, M. et al. Urinary C-X-C motif chemokine 10 independently improves the noninvasive diagnosis of antibody-mediated kidney allograft rejection. J. Am. Soc. Nephrol. 26, 2840–2851 (2015).
doi: 10.1681/ASN.2014080797
pubmed: 25948873
pmcid: 4625672
Tinel, C. et al. Development and validation of an optimized integrative model using urinary chemokines for noninvasive diagnosis of acute allograft rejection. Am. J. Transplant. 20, 3462–3476 (2020).
doi: 10.1111/ajt.15959
pubmed: 32342614