Recent Advances in the Management of Diabetic Kidney Disease: Slowing Progression

Abstract

Diabetic kidney disease (DKD) is a major cause of chronic kidney disease (CKD), and it heightens the risk of cardiovascular incidents. The pathogenesis of DKD is thought to involve hemodynamic, inflammatory, and metabolic factors that converge on the fibrotic pathway. Genetic predisposition and unhealthy lifestyle practices both play a significant role in the development and progression of DKD. In spite of the recent emergence of angiotensin receptors blockers (ARBs)/angiotensin converting enzyme inhibitor (ACEI), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid receptors antagonists (NS-MRAs), current therapies still fail to effectively arrest the progression of DKD. Glucagon-like peptide 1 receptor agonists (GLP-1RAs), a promising class of agents, possess the potential to act as renal protectors, effectively slowing the progression of DKD. Other agents, including pentoxifylline (PTF), selonsertib, and baricitinib hold great promise as potential therapies for DKD due to their anti-inflammatory and antifibrotic properties. Multidisciplinary treatment, encompassing lifestyle modifications and drug therapy, can effectively decelerate the progression of DKD. Based on the treatment of heart failure, it is recommended to use multiple drugs in combination rather than a single-use drug for the treatment of DKD. Unearthing the mechanisms underlying DKD is urgent to optimize the management of DKD. Inflammatory and fibrotic factors (including IL-1, MCP-1, MMP-9, CTGF, TNF-a and TGF-β1), along with lncRNAs, not only serve as diagnostic biomarkers, but also hold promise as therapeutic targets. In this review, we delve into the potential mechanisms and the current therapies of DKD. We also explore the additional value of combing these therapies to develop novel treatment strategies. Drawing from the current understanding of DKD pathogenesis, we propose HIF inhibitors, AGE inhibitors, and epigenetic modifications as promising therapeutic targets for the future.

Cross-Domain Text Mining of Pathophysiological Processes Associated with Diabetic Kidney Disease

“…The cellular signaling responses include growth factor signaling, the response to nitric oxide, the response to oxidative stress, the cytokine response, macrophage signaling, the TLR pathway, the T-cell-mediated response, NFκB factor activity, ERK/MAPK signaling, the JAK/STAT pathway, the WNT/β-catenin pathway, and NADPH oxidase activity. Several of these pathways are known to be implicated in GEC injury, inflammation, and fibrosis associated with DKD [6,8,11,17]. Similarly, the analyses suggested that the apoptotic processes, the response to cytokines, the T-cell-mediated response, the immune response, calcium channel activity, and growth factor signaling were the most frequent and active biological processes in DKD (Figures 6 and 7).…”

“…Metabolic abnormalities activate the mononuclear phagocyte system, which releases pro-inflammatory cytokines and paracrine signals, leading to immune cell infiltration [6][7][8][9]. In the early stages of diabetes, glomerular and tubular cells have increased expression of tumor necrosis factor (TNF) α, interleukin (IL)-6, IL-1, and adhesion molecules [10,11]. Previous experimental studies showed that hyperglycemia promotes the imbalance in macrophage phenotypes and chronic glucose exacerbates the regulation of inflammatory responses [12,13].…”