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dc.contributor.authorKirkwood, John
dc.contributor.authorSmallwood, Miranda
dc.contributor.authorWinyard, Paul G.
dc.contributor.authorKnight, Beatrice
dc.contributor.authorShore, Angela
dc.contributor.authorGilchrist, Mark
dc.date.accessioned2021-04-20T11:35:30Z
dc.date.available2021-04-20T11:35:30Z
dc.date.issued2020-10-20
dc.identifier.citationRiddell A et al. Urinary nitrate concentration as a marker for kidney transplant rejection. BMC Nephrol. 2020 Oct 20;21(1):441.en_US
dc.identifier.pmid33081704
dc.identifier.doi10.1186/s12882-020-02096-x
dc.identifier.urihttps://rde.dspace-express.com/handle/11287/621709
dc.description.abstractBackground: Early identification and treatment of kidney transplant rejection episodes is vital to limit loss of function and prolong the life of the transplanted kidney and recipient. Current practice depends on detecting a creatinine rise. A biomarker to diagnose transplant rejection at an earlier time point than current practice, or to inform earlier decision making to biopsy, could be transformative. It has previously been shown that urinary nitrate concentration is elevated in renal transplant rejection. Nitrate is a nitric oxide (NO) oxidation product. Transplant rejection upregulates NO synthesis via inducible nitric oxide synthase leading to elevations in urinary nitrate concentration. We have recently validated a urinary nitrate concentration assay which could provide results in a clinically relevant timeframe. Our aim was to determine whether urinary nitrate concentration is a useful tool to predict renal transplant rejection in the context of contemporary clinical practice. Methods: We conducted a prospective observational study, recruiting renal transplant participants over an 18-month period. We made no alterations to the patients' clinical care including medications, immunosuppression, diet and frequency of visits. We collected urine samples from every clinical attendance. We assessed the urinary nitrate to creatinine ratio (uNCR) between patient groups: routine attendances, biopsy proven rejection, biopsy proven no rejection and other call backs. uNCR was examined over time for those with biopsy proven transplant rejection. These four groups were compared using an ANOVA test. Results: A total of 2656 samples were collected. uNCR during biopsy proven rejection, n = 15 (median 49 μmol/mmol, IQR 23-61) was not significantly different from that of routine samples, n = 164 (median 55 μmol/mmol, IQR 37-82) (p = 0.55), or biopsy proven no rejection, n = 12 (median 39 μmol/mmol, IQR 21-89) (P = 0.77). Overall uNCR was highly variable with no diagnostic threshold for kidney transplant rejection. Furthermore, within-patient uNCR was highly variable over time, and thus it was not possible to produce individualised patient thresholds to identify rejection. The total taking Tacrolimus was 204 patients, with no statistical difference between the uNCR of all those on Tacrolimus, against those not, p = 0.18. Conclusion: The urinary nitrate to creatinine ratio is not a useful biomarker for renal transplant rejection.en_US
dc.language.isoenen_US
dc.publisherBioMed Centralen_US
dc.relation.urlhttps://www.biomedcentral.com/1471-2369/21/441en_US
dc.rights© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver hhttp://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the dataen_US
dc.rightsCC0 1.0 Universal*
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.subjectBiomarkeren_US
dc.subjectKidneyen_US
dc.subjectNitrateen_US
dc.subjectRejectionen_US
dc.subjectTransplanten_US
dc.titleUrinary nitrate concentration as a marker for kidney transplant rejectionen_US
dc.typeJournal Articleen_US
dc.identifier.journalBMC Nephrologyen_US
dc.identifier.pmcidPMC7576839
dc.description.noteThis article is available to RD&E staff via NHS OpenAthens. Click on the Publisher URL, and log in with NHS OpenAthens if prompted.en_US
dc.description.fundingWe thank the Mason Medical Research Trust for supporting this work. Funding was provided for research nurse time, technician time, and laboratory skills and consumables for processing the samples.en_US
dc.type.versionPublisheden_US
dc.description.admin-notepublished version, accepted versionen_US


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© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
The Creative Commons Public Domain Dedication waiver hhttp://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data
Except where otherwise noted, this item's license is described as © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver hhttp://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data