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2017 ; 8
(3
): 261-271
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Mechanisms of metabolic memory and renal hypoxia as a therapeutic target in
diabetic kidney disease
#MMPMID28097824
Hirakawa Y
; Tanaka T
; Nangaku M
J Diabetes Investig
2017[May]; 8
(3
): 261-271
PMID28097824
show ga
Diabetic kidney disease (DKD) is a worldwide public health problem. The
definition of DKD is under discussion. Although the term DKD was originally
defined as 'kidney disease specific to diabetes,' DKD frequently means chronic
kidney disease with diabetes mellitus and includes not only classical diabetic
nephropathy, but also kidney dysfunction as a result of nephrosclerosis and other
causes. Metabolic memory plays a crucial role in the progression of various
complications of diabetes, including DKD. The mechanisms of metabolic memory in
DKD are supposed to include advanced glycation end-products, deoxyribonucleic
acid methylation, histone modifications and non-coding ribonucleic acid including
micro ribonucleic acid. Regardless of the presence of diabetes mellitus, the
final common pathway in chronic kidney disease is chronic kidney hypoxia, which
influences epigenetic processes, including deoxyribonucleic acid methylation,
histone modification, and conformational changes in micro ribonucleic acid and
chromatin. Therefore, hypoxia and oxidative stress are appropriate targets of
therapies against DKD. Prolyl hydroxylase domain inhibitor enhances the defensive
mechanisms against hypoxia. Bardoxolone methyl protects against oxidative stress,
and can even reverse impaired renal function; a phase 2 trial with considerable
attention to heart complications is currently ongoing in Japan.