Manuel Sanchez1,2,3, Ronan Roussel1,3,4, Samy Hadjadj5,6,7, Abdul Moutairou1, Michel Marre1,3,4, Gilberto Velho1, Kamel Mohammedi8,9. 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.
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.
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