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

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.

Kidney Inflammation, Injury and Regeneration

“…In addition, the potential of cell-based therapy approaches that use mesenchymal stromal/stem cells (MSCs) or their derivates is summarized [23][24][25]. This edition is complemented by a series of reviews that deal with the current data situation on other very specific topics like diabetes and diabetic nephropathy [26][27][28], as well as new therapeutic targets [29].In this Special Issue, twelve original research articles are presented that dealt with different questions and the research models used within. The findings of Mocker and co-workers demonstrate that renal chemerin expression, a chemoattractant adipokine, is associated with processes of inflammation and fibrosis during renal damage [2].…”

“…In addition, the potential of cell-based therapy approaches that use mesenchymal stromal/stem cells (MSCs) or their derivates is summarized [23][24][25]. This edition is complemented by a series of reviews that deal with the current data situation on other very specific topics like diabetes and diabetic nephropathy [26][27][28], as well as new therapeutic targets [29].…”

“…MSCs predominantly act through secreted factors, including microRNAs that are contained within extracellular vesicles, cytoprotective effects anti-inflammatory effects, anti-apoptotic effects, and the suppression of oxidative stress. In addition, further reviews summarized the inflammation-mediated mechanisms or the inflammasome in various renal diseases [15][16][17][18]26,27]. Very interesting and new approaches shed a light on the role of non-coding RNAs, either in the progression of glomerular or tubulointerstitial kidney diseases [20] or as new therapeutic targets or biomarkers for fibrotic changes [29].…”

Targeting Inflammation in Diabetic Kidney Disease: Is There a Role for Pentoxifylline?

“…The source of cytokine production by the kidneys in DM is from both infiltrating macrophages and resident kidney cells. Production of reactive oxygen species (ROS), pro-inflammatory factors, and certain growth factors (such as transforming growth factor-beta) can induce renal damage, and macrophage depletion studies in rodent models have shown a causal role for macrophages in the progression of DKD [21]. In a human biopsy study, Nguyen et al reported that accumulation of macrophages was more prevalent in the interstitium than in the glomeruli and that interstitial macrophages correlated strongly with proteinuria, decline in renal function, and extent of interstitial fibrosis [22].…”

“…Several approaches have been proposed to treat inflammation in DKD, including lifestyle modifications (diet and exercise) and medications. Anti-inflammatory effects may explain some of the benefits of SGLT2 inhibitors and possibly also GLP-1 receptor agonists [21]. In addition, three large randomized controlled trials specifically targeting inflammation in DKD have been or are currently being performed.…”