Urinary excretion of 8-oxo-7, 8-dihydro-2'-deoxyguanosine as a predictor of the development of diabetic nephropathy.
OBJECTIVE
The increased oxidative stress in diabetes is known to contribute to the progression of diabetes and its complications. We have reported a significant relation between the content of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a product of oxidative DNA damage in urine or leukocytes and the severity of diabetic nephropathy and retinopathy [1]. We investigated whether 8-oxodG in urine or leukocytes is associated with the progression of diabetic nephropathy.


METHODS
We measured urinary 8-oxodG contents at entry and carried out a prospective longitudinal study to assess the progression of nephropathy over 5 years.


RESULTS
There was a significant progression of diabetic nephropathy in the patients with higher excretion of 8-oxodG in urine compared with the patients with moderate or lower excretion of 8-oxodG. There was no significant association between the leukocyte 8-oxodG contents and the development of nephropathy. The multivariate logistic regression analysis suggests that the urinary 8-oxodG was the strongest predictor of nephropathy among several known risk factors.


CONCLUSIONS
This study provides evidence that increased oxidative stress has a primary role in the pathogenesis of diabetic nephropathy. A local enhancement of oxidative stress in diabetic kidney might explain the possible linkage between the increased urinary excretion of 8-oxodG and the development of nephropathy. 8-oxodG in urine is a useful clinical marker to predict the development of diabetic nephropathy in diabetic patients.
Hinokio
Y
Y
Department of Molecular Metabolism and Diabetes, Tohoku University, Graduate School of Medicine, Sendai, Japan.
Suzuki
S
S
Hirai
M
M
Suzuki
C
C
Suzuki
M
M
Toyota
T
T
D017668:Age of Onset; D015415:Biomarkers / Q000652:urine*; D003839:Deoxyadenosines / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000652:urine; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012016:Reference Values; D013997:Time Factors
D015415:Biomarkers; D003839:Deoxyadenosines; C078251:2'-deoxy-7,8-dihydro-8-oxoadenosine