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

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

Author information

1
Inserm, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France.
2
Department of Geriatric Medicine, Assistance Publique Hôpitaux de Paris, Bichat Hospital, Paris, France.
3
UFR de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
4
Department of Diabetology, Endocrinology and Nutrition, Assistance Publique Hôpitaux de Paris, Bichat Hospital, DHU FIRE, 46 rue Henri Huchard, 75877, Paris Cedex 18, France.
5
Department of Endocrinology and Diabetology, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
6
Inserm, Research Unit 1082, Poitiers, France.
7
Université de Poitiers, UFR de Médecine et Pharmacie, Poitiers, France.
8
Inserm, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France. km.mmohammedi@gmail.com.
9
Department of Diabetology, Endocrinology and Nutrition, Assistance Publique Hôpitaux de Paris, Bichat Hospital, DHU FIRE, 46 rue Henri Huchard, 75877, Paris Cedex 18, France. km.mmohammedi@gmail.com.

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

PMID:
29185011
DOI:
10.1007/s00125-017-4510-1
[Indexed for MEDLINE]

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