Recent advances in drug discovery for diabetic kidney disease

ABSTRACT

Introduction

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD), and 40% of patients with diabetes develop DKD. Although some pathophysiological mechanisms and drug targets of DKD have been described, the effectiveness or clinical usefulness of such treatment has not been well validated. Therefore, searching for new targets and potential therapeutic candidates has become an emerging research area.

Areas covered

The pathophysiological mechanisms, new drug targets and potential therapeutic compounds for DKD are addressed in this review.

Expert opinion

Although preclinical and clinical evidence has shown some positive results for controlling DKD progression, treatment regimens have not been well developed to reduce the mortality in patients with DKD globally. Therefore, the discovery of new therapeutic targets and effective target-based drugs to achieve better and safe treatment are urgently required. Preclinical screening and clinical trials for such drugs are needed.

KEYWORDS:

• Diabetic complications
• diabetic nephropathy
• drug discovery
• endothelin receptor blockers
• oxidative stress
• renin-angiotensin-aldosterone system
• SGLT-2 inhibitors

Article highlights

• Diabetic kidney disease (DKD) is the single most common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD), which is clinically characterized by persistent albuminuria of 30-300mg/day.

• 40% of patients with diabetes develop DKD.

• Multiple pathophysiological mechanisms have been proposed; therefore, the treatment could be difficult with single-drug therapy.

• Current treatment of DKD is not able to stop its pathological progression completely and reduce mortality rate.

• The discovery of new therapeutic targets and effective target-based drugs to achieve better and safe treatment are urgently required.

The box summarizes key points contained in the article.

Declaration of interest

CC Danta is as a post-doctoral research associate for SZ Xu who received support via grant No 115,974 supported from the Innovative Medicines Initiative 2 Joint Undertaking. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115974. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme together with the European Federation of Pharmaceutical Industries and Associations (EFPIA) and the JDRF (to SZ Xu).