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Review
. 2019 Jul 10;20(14):3393.
doi: 10.3390/ijms20143393.

Unraveling the Role of Inflammation in the Pathogenesis of Diabetic Kidney Disease

Keiichiro Matoba  1 , Yusuke Takeda  2 , Yosuke Nagai  2 , Daiji Kawanami  3 , Kazunori Utsunomiya  4 , Rimei Nishimura  2
Affiliations
Review

Unraveling the Role of Inflammation in the Pathogenesis of Diabetic Kidney Disease

Keiichiro Matoba et al. Int J Mol Sci. .

Abstract

Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease (ESRD) and is therefore a major burden on the healthcare system. Patients with DKD are highly susceptible to developing cardiovascular disease, which contributes to increased morbidity and mortality rates. While progress has been made to inhibit the acceleration of DKD, current standards of care reduce but do not eliminate the risk of DKD. There is growing appreciation for the role of inflammation in modulating the process of DKD. The focus of this review is on providing an overview of the current status of knowledge regarding the pathologic roles of inflammation in the development of DKD. Finally, we summarize recent therapeutic advances to prevent DKD, with a focus on the anti-inflammatory effects of newly developed agents.

Keywords: diabetic kidney disease; diabetic nephropathy; inflammation; signaling cascade.

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Conflict of interest statement

Kazunori Utsunomiya has received research support from Terumo, Novo Nordisk Pharma, Taisho Pharmaceutical, Böehringer Ingelheim, Kyowa Hakko Kirin, Sumitomo Dainippon Pharma, and Ono Pharmaceutical as well as speaker honoraria from Tanabe Pharma, Sanofi Kabushiki Kaisya, Sumitomo Dainippon Pharma, Eli Lilly, and Böehringer Ingelheim. Rimei Nishimura has received speaker honoraria from Astellas Pharma, Nippon Boehringer Ingelheim, Eli Lilly Japan Kabushiki Kaisya, Kissei Pharmaceutical, Medtronic Japan, MSD, Novartis Pharma Kabushiki Kaisya, Novo Nordisk Pharma, Sanofi Kabushiki Kaisya, and Takeda Pharmaceutical and contract research fees for collaborative research with the Japan Diabetes Foundation.

Figures

Figure 1
Figure 1
In the diabetic kidney, advanced glycation end products (AGEs) and oxidative stress activate a variety of signaling cascades to induce monocyte infiltration. In addition, chemokines drive inflammation, leading to macrophage-mediated tissue injury. DKD, Diabetic kidney disease; RAGE, receptor for AGE; VCAM1, vascular cell adhesion molecule 1; ICAM1, intercellular adhesion molecule 1; JAK-STAT, Janus kinase/signal transducer and activator of transcription; NF-κB, Nuclear factor Κb; Nrf2, nuclear factor-2 erythroid related factor 2; TNF-α, tumor necrosis factor α; TGF-β, transforming growth factor β.
See this image and copyright information in PMC

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