Plasma Concentrations of 8-hydroxy-2'-deoxyguanosine and Risk of Kidney Disease and Death in Individuals with Type 1 Diabetes

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2017 Nov 30

PMID 29185011

Citations 18

Authors

Manuel Sanchez

Ronan Roussel

Samy Hadjadj

Abdul Moutairou

Michel Marre

Gilberto Velho

Kamel Mohammedi

Affiliations

Soon will be listed here.

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 1.73 m; tertile 2, 88 [82, 94] ml min 1.73 m; tertile 3, 74 [68, 80] ml min 1.73 m; 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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