Plasma concentrations of 8-hydroxy-2′-deoxyguanosine and risk of kidney disease and death in individuals with type 1 diabetes
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Oxidative stress is involved in the pathogenesis of diabetic kidney disease. We evaluated the association between 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of DNA oxidative damage, and end-stage renal disease (ESRD) or death in individuals with type 1 diabetes.
Plasma 8-OHdG concentrations were measured at baseline in participants with type 1 diabetes from GENEDIAB (n = 348) and GENESIS (n = 571) cohorts. A follow-up was conducted in 205 and 499 participants for a mean ± SD duration of 8.9 ± 2.3 years and 5.2 ± 1.9 years, respectively. We tested associations between 8-OHdG concentrations and urinary albumin concentration (UAC) or eGFR at baseline, and the risk of ESRD or all-cause mortality during follow-up. Analyses were performed in pooled cohorts.
The highest UAC (geometric mean [95% CI]) was observed in the third 8-OHdG tertile (tertile 1, 9 [6, 13] mg/l; tertile 2, 10 [7, 16] mg/l; tertile 3, 16 [10, 25] mg/l; p = 0.36 for tertile 1 vs tertile 2 and p = 0.003 for tertile 3 vs tertile 1) after adjustment for potential confounding covariates. The lowest eGFR (mean [95% CI]) was observed in the third tertile (tertile 1, 87 [82, 93] ml min−1 1.73 m−2; tertile 2, 88 [82, 94] ml min−1 1.73 m−2; tertile 3, 74 [68, 80] ml min−1 1.73 m−2; p = 0.61 for tertile 1 vs tertile 2; p < 0.001 for tertile 3 vs tertile 1). ESRD and death occurred in 48 and 64 individuals, respectively. The HR for ESRD, but not death, was higher in the third tertile than in the first (tertile 2 vs tertile 1, 1.45 [0.45, 5.04], p = 0.54; tertile 3 vs tertile 1, 3.05 [1.16, 9.60], p = 0.02) after multiple adjustments.
Higher plasma concentrations of 8-OHdG were independently associated with increased risk of kidney disease in individuals with type 1 diabetes, suggesting that this marker can be used to evaluate the progression of diabetic kidney disease.
KeywordsAlbuminuria End-stage renal disease Glomerular filtration rate Kidney disease Mortality Oxidative stress Type 1 diabetes
Advanced oxidation protein products
Angiotensin receptor blocker
End-stage renal disease
Génétique de la Néphropathie Diabétique study
The GENESIS France–Belgium study
Reactive oxygen species
Urinary albumin concentration
The datasets analysed during the current study are not publicly available due to consideration of intellectual property, many ongoing active collaborations and to continuing analyses by the study investigators, but are available from the principal investigator on reasonable request.
KM was supported by grants from the ‘Fibrosis, Inflammation, Remodeling in cardiovascular, respiratory and renal diseases’ hospital and university department (DHU FIRE).
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
MS and KM designed the study, researched data and drafted the manuscript. AM researched data and reviewed/edited the manuscript. RR, SH, MM and GV designed the study, researched data, contributed to the discussion and reviewed/edited the manuscript. KM is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analyses. All authors approved the current version of the manuscript.
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