Kidney Research and Clinical Practice

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Editorial

Diabetic kidney disease, revisited: where do we stand?

Dae Ryong Cha

Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea

Study Summary: Diabetic kidney disease (DKD) is the leading cause of end stage renal disease and a major cause of morbidity and mortality in diabetic patients. Since complexity of mechanisms of DKD, there are still high medical unmet needs for the management of DKD. Although recent trials provides some promise, the residual risk for progression of renal disease still high. In this paper, we briefly introduce current therapeutic strategies in DKD, role of NADPH oxidase and development of Nox inhibitor in DKD, adenosine receptors as emerging therapeutic targets in DKD, new molecular targets in DKD, and promising novel biomarkers for DKD.

Suggestion for future study: Although there are huge progress in the management of DKD, there is still high risk for the progression of DKD. It is, therefore, necessary to identify new molecular target and biomarker to overcome the current limitation.

Review Articles

Novel biomarkers for diabetic kidney disease

Chan-Young Jung, Tae-Hyun Yoo

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea

Study Summary: Although diabetic kidney disease (DKD) remains one of the leading causes of reduced lifespan in patients with diabetes mellitus, its prevalence has failed to decline over the past 30 years. In order to identify those at high risk of developing DKD and disease progression at an early stage, extensive research has been ongoing in the search for prognostic and surrogate endpoint biomarkers for DKD. This review article describes the biomarkers used in current practice and their limitations, and then summarizes the current status of novel biomarkers for DKD.

Suggestion for future study: Although novel biomarkers have enormous potential in the field of DKD, future studies should not only look into using these biomarkers as surrogates of study endpoints, but also obtain comparable and reproducible data among collaborators.

Adenosine receptors as emerging therapeutic targets for diabetic kidney disease

Eun Seon Pak, Hunjoo Ha et al.

Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea

Study Summary: Adenosine and adenosine receptors (ARs) play important roles in regulating homeostatic kidney function, such as kidney blood flow, glomerular filtration rate, renin release, as well as tubuloglomerular feedback. However, chronically increased adenosine and ARs contribute to various tissue injuries including diabetic kidney disease (DKD). This review summarizes our current understanding on the (patho)physiological role of adenosine and ARs and proposes AR modulators as a new therapeutic option to treat DKD.

Suggestion for future study: Protective effect of AR modulators has been shown in experimental DKD, yet future detailed mechanistic studies on the pharmacology of AR modulators remain to develop effective first-in-class AR modulator against DKD.

NADPH oxidase inhibitor development for diabetic nephropathy through water tank model

Hye Eun Lee, Yongseok Choi, Yun Soo Bae et al.

Celros Biotech, Seoul, Republic of Korea
Institute of Life Science and Natural Resources, Korea University, Seoul, Republic of Korea

Study Summary: Several lines of evidences suggest that transient reactive oxygen species (ROS) generation serves as a secondary messenger in cell signaling. We discusses two faces of ROS functions in cell physiology through water tank model. Receptor-mediated NADPH oxidase (Nox) stimulates transient ROS generation regulating normal physiology including cell growth, differentiation and tissue regeneration, whereas uncontrolled ROS generation by overexpression and hyperactivation of Nox is associated with various diseases such as acute kidney injury and diabetic nephropathy (DN). This review discusses the theoretical basis for development of Nox inhibitor as a regulator of ROS homeostasis to provide emerging therapeutic opportunities for DN.

Suggestion for future study: Uncontrolled ROS generation through over-activation of Nox is associated with pathogenesis of DN. Uncontrolled Nox activation should be suppressed by Nox inhibitors as an emerging therapy for DN. We believe that these Nox inhibitors provide new hope for DN patients.

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