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

Diabetologia. 2018 Apr;61(4):977-984. doi: 10.1007/s00125-017-4510-1. Epub 2017 Nov 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adult
  • Cross-Sectional Studies
  • DNA Damage
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / blood
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / mortality
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Humans
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / mortality
  • Male
  • Middle Aged
  • Oxidative Stress
  • Oxygen / chemistry
  • Prospective Studies
  • Risk Factors
  • Sensitivity and Specificity

Substances

  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine
  • Oxygen