Pathogenesis of Diabetic Kidney Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 1220

Special Issue Editor


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Guest Editor
Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Interests: her major research interest has been in the field of exploring pathogenesis of diabetic kidney disease by utilizing molecular profiling of specific cell types in murine and human kidneys. Her lab is currently deploying cutting-edge technologies to deeply understand cell type specific response and cellular crosstalk after kidney injuries, in particular, single cell RNA-seq and spatial transcriptomes

Special Issue Information

Dear Colleagues,

Diabetic kidney disease (DKD) is a significant and growing health concern, being one of the most common complications of diabetes and a leading cause of chronic kidney disease and end-stage renal failure worldwide. Recent studies have unveiled new findings in the pathogenesis of DKD, including novel insights into the roles of genetic modification, inflammatory pathways, and metabolic dysfunction. These discoveries underscore the complexity of DKD and highlight the need for continued research to develop more effective diagnostic and therapeutic strategies.
This Special Issue aims to gather cutting-edge research and comprehensive reviews that explore the multifaceted pathogenesis of diabetic kidney disease. We invite all scientists working in the field of diabetic kidney disease to participate in this Special Issue. Original research articles, reviews, and communications related to diabetic kidney disease are welcome, including molecular and cellular mechanisms, inflammation and oxidative stress, metabolic dysregulation, renal hemodynamics and hypertension, biomarkers and early diagnostic tools, and innovative therapeutic targets and strategies. By addressing these critical areas, this Special Issue seeks to enhance our understanding of DKD pathogenesis and to identify novel therapeutic targets that could lead to improved patient outcomes.
We look forward to your submissions and to advancing the field of diabetic kidney disease research together.

Dr. Jia Fu
Guest Editor

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Keywords

  • diabetic kidney disease (DKD)
  • molecular mechanism, oxidative stress
  • chronic kidney disease
  • pathogenesis
  • diagnostic and therapeutic strategies
  • inflammation
  • metabolic dysfunction

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Published Papers (1 paper)

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Research

18 pages, 10535 KiB  
Article
Finerenone Alleviates Over-Activation of Complement C5a-C5aR1 Axis of Macrophages by Regulating G Protein Subunit Alpha i2 to Improve Diabetic Nephropathy
by Zi-Han Li, Zi-Jun Sun, Sydney C. W. Tang, Ming-Hui Zhao, Min Chen and Dong-Yuan Chang
Cells 2025, 14(5), 337; https://doi.org/10.3390/cells14050337 - 26 Feb 2025
Viewed by 761
Abstract
Diabetic nephropathy (DN), one of the most common complications of diabetes mellitus (DM), accounts for a major cause of chronic kidney disease (CKD) worldwide, with a complicated pathogenesis and limited effective strategies nowadays. The mineralocorticoid receptor (MR) is a classical ligand-activated nuclear transcription [...] Read more.
Diabetic nephropathy (DN), one of the most common complications of diabetes mellitus (DM), accounts for a major cause of chronic kidney disease (CKD) worldwide, with a complicated pathogenesis and limited effective strategies nowadays. The mineralocorticoid receptor (MR) is a classical ligand-activated nuclear transcription factor. It is expressed in the renal intrinsic and immune cells, especially macrophages. Over-activation of the MR was observed in patients with DN and was associated with DN prognosis. The renoprotective role of a new generation of non-steroidal selective mineralocorticoid receptor antagonist (MRA), finerenone, has been confirmed in DM and CKD patients. However, the mechanism by which finerenone improves renal inflammation in DN has yet to be completely understood. It was found in this research that the oral administration of finerenone attenuated the kidney injuries in established DN in db/db mice, and particularly improved the pathological changes in the renal tubulointerstitia. Specifically, finerenone inhibited the over-activation of the MR in macrophages, thereby reducing the expression of G protein subunit alpha i2 (GNAI2, Gnαi2), a key downstream component of the C5aR1 pathway. Animal experiments demonstrated that C5aR1 knockout alleviated renal injuries, confirming the critical pathogenic role of C5aR1 in DN. Moreover, finerenone mitigated inflammatory and chemotaxis responses by downregulating Gnαi2 in macrophages. These effects were reflected by reduced expressions of the pro-inflammatory chemokines CXCL15 and CCL2, the regulation of macrophage polarization and improvements in apoptosis. This study intends to understand the protective role of finerenone in DN, which is conducive to revealing the pathophysiological mechanism of DN and further optimizing the treatment of DN patients. Full article
(This article belongs to the Special Issue Pathogenesis of Diabetic Kidney Disease)
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