Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine

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@article{70b6e36a8f834b01924fe925fbaf9634,
title = "Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine",
abstract = "Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.",
author = "Lars Barregard and Peter Moller and Trine Henriksen and Vilas Mistry and Gudrun Koppen and {Rossner Jr.}, Pavel and Sram, {Radim J.} and Allan Weimann and Poulsen, {Henrik E.} and Robert Nataf and Roberta Andreoli and Paola Manini and Tim Marczylo and Patricia Lam and Evans, {Mark D.} and Hiroshi Kasai and Kazuaki Kawai and Yun-Shan Li and Kazuo Sakai and Rajinder Singh and Friederike Teichert and Farmer, {Peter B.} and Rafal Rozalski and Daniel Gackowski and Agnieszka Siomek and Saez, {Guillermo T.} and Concha Cerda and {Broberg Palmgren}, Karin and Christian Lindh and Bakhtiar Hossain and Siamak Haghdoost and Chiung-Wen Hu and Mu-Rong Chao and Kuen-Yuh Wu and Hilmi Orhan and Nilufer Senduran and Smith, {Raymond J.} and Santella, {Regina M.} and Yali Su and Czarina Cortez and Susan Yeh and Ryszard Olinski and Steffen Loft and Cooke, {Marcus S.}",
year = "2013",
doi = "10.1089/ars.2012.4714",
language = "English",
volume = "18",
pages = "2377--2391",
journal = "Antioxidants and Redox Signaling",
issn = "1557-7716",
publisher = "Mary Ann Liebert, Inc.",
number = "18",

}