Article ; Online: Kidney Fibrosis and Oxidative Stress: From Molecular Pathways to New Pharmacological Opportunities.
2024 Volume 14, Issue 1
Abstract: Kidney fibrosis, diffused into the interstitium, vessels, and glomerulus, is the main pathologic feature associated with loss of renal function and chronic kidney disease (CKD). Fibrosis may be triggered in kidney diseases by different genetic and ... ...
| Abstract | Kidney fibrosis, diffused into the interstitium, vessels, and glomerulus, is the main pathologic feature associated with loss of renal function and chronic kidney disease (CKD). Fibrosis may be triggered in kidney diseases by different genetic and molecular insults. However, several studies have shown that fibrosis can be linked to oxidative stress and mitochondrial dysfunction in CKD. In this review, we will focus on three pathways that link oxidative stress and kidney fibrosis, namely: (i) hyperglycemia and mitochondrial energy imbalance, (ii) the mineralocorticoid signaling pathway, and (iii) the hypoxia-inducible factor (HIF) pathway. We selected these pathways because they are targeted by available medications capable of reducing kidney fibrosis, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (MRAs), and HIF-1alpha-prolyl hydroxylase inhibitors. These drugs have shown a reduction in oxidative stress in the kidney and a reduced collagen deposition across different CKD subtypes. However, there is still a long and winding road to a clear understanding of the anti-fibrotic effects of these compounds in humans, due to the inherent practical and ethical difficulties in obtaining sequential kidney biopsies and the lack of specific fibrosis biomarkers measurable in easily accessible matrices like urine. In this narrative review, we will describe these three pathways, their interconnections, and their link to and activity in oxidative stress and kidney fibrosis. |
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| MeSH term(s) | Humans ; Kidney/metabolism ; Renal Insufficiency, Chronic/pathology ; Oxidative Stress ; Collagen/metabolism ; Fibrosis |
| Chemical Substances | Collagen (9007-34-5) |
| Language | English |
| Publishing date | 2024-01-22 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Review |
| ZDB-ID | 2701262-1 |
| ISSN | 2218-273X ; 2218-273X |
| ISSN (online) | 2218-273X |
| ISSN | 2218-273X |
| DOI | 10.3390/biom14010137 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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