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Diabetologia

, Volume 61, Issue 4, pp 977–984 | Cite as

Plasma concentrations of 8-hydroxy-2′-deoxyguanosine and risk of kidney disease and death in individuals with type 1 diabetes

  • Manuel Sanchez
  • Ronan Roussel
  • Samy Hadjadj
  • Abdul Moutairou
  • Michel Marre
  • Gilberto Velho
  • Kamel Mohammedi
Article

Abstract

Aims/hypothesis

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.

Methods

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.

Results

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.

Conclusions/interpretation

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.

Keywords

Albuminuria End-stage renal disease Glomerular filtration rate Kidney disease Mortality Oxidative stress Type 1 diabetes 

Abbreviations

AOPP

Advanced oxidation protein products

ARB

Angiotensin receptor blocker

ESRD

End-stage renal disease

GENEDIAB

Génétique de la Néphropathie Diabétique study

GENESIS

The GENESIS France–Belgium study

IQR

Interquartile range

8-OHdG

8-Hydroxy-2′-deoxyguanosine

ROS

Reactive oxygen species

UAC

Urinary albumin concentration

Notes

Data availability

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.

Funding

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.

Contribution statement

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.

Supplementary material

125_2017_4510_MOESM1_ESM.pdf (301 kb)
ESM (PDF 300 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Manuel Sanchez
    • 1
    • 2
    • 3
  • Ronan Roussel
    • 1
    • 3
    • 4
  • Samy Hadjadj
    • 5
    • 6
    • 7
  • Abdul Moutairou
    • 1
  • Michel Marre
    • 1
    • 3
    • 4
  • Gilberto Velho
    • 1
  • Kamel Mohammedi
    • 1
    • 4
  1. 1.Inserm, UMRS 1138, Centre de Recherche des CordeliersParisFrance
  2. 2.Department of Geriatric Medicine, Assistance Publique Hôpitaux de ParisBichat HospitalParisFrance
  3. 3.UFR de MédecineUniversité Paris Diderot, Sorbonne Paris CitéParisFrance
  4. 4.Department of Diabetology, Endocrinology and Nutrition, Assistance Publique Hôpitaux de ParisBichat Hospital, DHU FIREParis Cedex 18France
  5. 5.Department of Endocrinology and DiabetologyCentre Hospitalier Universitaire de PoitiersPoitiersFrance
  6. 6.Inserm, Research Unit 1082PoitiersFrance
  7. 7.Université de Poitiers, UFR de Médecine et PharmaciePoitiersFrance

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