Iron metabolism and chronic inflammation in IgA nephropathy

Abstract

IgA nephropathy (IgAN), an immune-mediated chronic inflammatory kidney disease, is the most common primary glomerular disease in Asia, especially in China and Japan. The pathogenesis of IgAN is complex, and the main cause of IgAN is explained by the ‘multiple hit’ theory, which states that the deposition of immune complexes in renal mesangial cells induces chronic inflammation that leads to kidney damage. Chronic inflammation is associated with iron metabolism, which also plays an essential role in the pathogenesis, progression, diagnosis and prognosis of IgAN. Overall, this review aimed to explore the application of iron metabolism in IgAN by systematically elaborating the relationship between iron metabolism and chronic inflammation in IgAN to speculate on the possible diagnostic and therapeutic significance of iron metabolism indicators in IgAN.

Mendelian Randomization Analysis of Systemic Iron Status and Risk of Different Types of Kidney Disease

“…More and more studies have proven that iron is related to kidney disease; perhaps, iron can provide a potential strategy for treating kidney disease. Observational studies have recognized the associations between biomarkers of iron and several autoimmune diseases, such as systemic lupus erythematosus [62], adult Still's disease [63], and systemic juvenile rheumatoid arthritis [64], as well as IgAN [65]; however a causal relationship is yet to be defined. There is evidence from experimental and clinical studies that increased non-transferrin bound iron (NTBI) is a risk factor for the severity of AKI and poor clinical outcomes [66].…”

Emerging significance and therapeutic targets of ferroptosis: a potential avenue for human kidney diseases

“…Previous studies have demonstrated that the relationship between ferroptosis and iron metabolism is mutually reinforcing and complementary. IgAN induces the dysregulation of iron metabolism, and disturbed iron homeostasis aggravates IgAN progression [ 266 , 267 ]. A recent study demonstrated that approximately 40% of IgAN patients presented with iron deposition in renal tissues [ 266 ].…”

“…TFR1 mediates iron homeostasis by regulating iron uptake through the endocytosis of iron-loaded TF. Urinary TF has been positively linked with endothelial cell hyperplasia, mesangial cell hyperplasia, tubular atrophy or interstitial fibrosis, according to the Oxford classification of IgAN patients [ 267 ]. Recent studies have suggested that TFR1 functions as a specific ferroptosis marker and plays an essential role in ferroptosis [ 268 ].…”

“…Moreover, IgA1-CD89 complexes promoted the binding of sCD89 with TFR1 to induce the expression of transglutaminase 2 (TGase2) on the surface of HMCs, thereby facilitating the upregulation of TFR1 [ 272 ]. The levels of soluble transferrin receptor (sTFR), a fragment of TFR1 on the cell membrane secreted into the circulation, were obviously higher in the blood and urine of IgAN patients than in normal individuals [ 267 , 273 ]. Moreover, urinary sTFR levels were markedly decreased when IgAN patients were in complete remission [ 270 ].…”

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

“…Indeed, tubular epithelial cell EVs loaded with functional cargoes such as chemokines, TGF-β1, CCL2 mRNA, and osteopontin transferred these cargoes to interstitial macrophages, aggravating kidney damage [ 145 ]. In kidney diseases such as IgA nephropathy [ 147 ] and diabetic kidney disease [ 148 ], increased inflammation leads to cellular oxidative damage. The spread of inflammation between tubules and renal interstitium may lead to significant kidney damage.…”