Recent advances in the understanding of renal inflammation and fibrosis in lupus nephritis

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.

α2AP is associated with the development of lupus nephritis through the regulation of plasmin inhibition and inflammatory responses

“…Severe LN is characterized by inflammatory glomerular lesions resulting in fibrosis and a loss of the renal function. 42 The chronic inflammation response is known to cause the development of fibrosis. 43 Fibrosis is characterized by the deposition of myofibroblasts and extracellular matrix.…”

Curcumin attenuates autoimmunity and renal injury in an experimental model of systemic lupus erythematosus

“…The kidneys have a central role in the long-term control of blood pressure, and the lower GFR with increased BUN in SLE mice are consistent with renal function changes that contribute to hypertension. Hypertension is prevalent among SLE patients and is a contributing factor to cardiovascular morbidity and mortality (Anders & Weening, 2013;Mayes et al, 2003;Yu, Gershwin, & Chang, 2014;Yung & Chan, 2012Yung, Ng, et al, 2017), and is evident in female NZBWF1 SLE mice (Han et al, 2015;Yung, Yap, & Chan, 2017). The present study demonstrates curcumin treatment had no significant effect on MAP in control or SLE mice.…”

An Exosomal Urinary miRNA Signature for Early Diagnosis of Renal Fibrosis in Lupus Nephritis

“…The exact mechanism of fibrosis in LN is unknown, but the persistence of wound-healing processes with prolonged production of growth factors, fibrogenic cytokines, and proteolytic enzymes, leading to increased synthesis and degradation of the extracellular matrix [47] seems to play a role. Previous studies in LN focused on the fibrotic role of miR-150 by targeting SOCS1, a negative regulator of profibrotic proteins [26] and miR-29c downregulation [25].…”