Abstract
Lupus nephritis is a potentially reversible cause of severe acute kidney injury and is an important cause of end-stage renal failure in Asians and patients of African or Hispanic descent. It is characterized by aberrant exaggerated innate and adaptive immune responses, autoantibody production and their deposition in the kidney parenchyma, triggering complement activation, activation and proliferation of resident renal cells, and expression of pro-inflammatory and chemotactic molecules leading to the influx of inflammatory cells, all of which culminate in destruction of normal nephrons and their replacement by fibrous tissue. Anti-double-stranded DNA (anti-dsDNA) antibody level correlates with disease activity in most patients. There is evidence that apart from mediating pathogenic processes through the formation of immune complexes, pathogenic anti-dsDNA antibodies can bind to resident renal cells and induce downstream pro-apoptotic, pro-inflammatory, or pro-fibrotic processes or a combination of these. Recent data also highlight the critical role of macrophages in acute and chronic kidney injury. Though clinically effective, current treatments for lupus nephritis encompass non-specific immunosuppression and the anti-inflammatory action of high-dose corticosteroids. The clinical and histological impact of novel biologics targeting pro-inflammatory molecules remains to be investigated. Insight into the underlying mechanisms that induce inflammatory and fibrotic processes in the kidney of lupus nephritis could present opportunities for more specific novel treatment options to improve clinical outcomes while minimizing off-target untoward effects. This review discusses recent advances in the understanding of pathogenic mechanisms leading to inflammation and fibrosis of the kidney in lupus nephritis in the context of established standard-of-care and emerging therapies.
Highlights
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) and is associated with a sixfold increase in mortality compared with the general population[1]
We reported that anti-double-stranded DNA (dsDNA) antibodies isolated from patients with LN during nephritic flare can induce secretion of pro-inflammatory mediators such as IL-6, IL-8, TNF-α, and monocyte chemoattractant protein-1 (MCP-1) through distinct mitogen-activated protein kinase (MAPK) pathways in cultured PTECs14,39 and contribute to the establishment of chemotactic gradients that permit infiltration of immune cells into the tubulo-interstitium
We reported that anti-dsDNA antibodies can induce both soluble and fibrillar fibronectin synthesis in mesangial cells and proximal tubular epithelial cells (PTECs) through increased protein kinase C (PKC) and MAPK signaling and TGF-β1, MCP-1, IL-6, IL-8, and TNF-α secretion[14,16]
Summary
Faculty Reviews are review articles written by the prestigious Members of Faculty Opinions. The articles are commissioned and peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations. Any comments on the article can be found at the end of the article
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.