About this Research Topic
Kidney stone formation is a common urological disorder causing significant morbidity and financial burden. The stone formation can lead to other renal and vascular diseases such as hypertension, chronic kidney disease, and end-stage renal disease. Kidney stones are mineral deposits, mostly in the pelvis, free or attached to the renal papillae. Calcium oxalate (CaOx) is the main component of approximately 80% of the kidney stones. Most idiopathic CaOx stones develop attached to sub-epithelial deposits of calcium phosphate (CaP) on the renal papillary surface, called Randall’s plaques (RP).
The development of RPs in the renal interstitium is considered as the first step in the development of the majority of idiopathic CaOx stones and cannot be accomplished simply through increased supersaturation of calcium and oxalate ions in the tubular fluid. It has been proposed that RP formation is similar to vascular calcification which is associated with the production of ROS, inflammation, and osteogenic changes.
Different studies indicate increased expression of genes related to inflammation, immunity, and complement activation pathways in the renal tissue of stone patients. Macrophages appear to be critically involved in this process. M1 related genes appear to be associated with the promotion of stone formation while M2 related genes with stone suppression. M2 macrophages phagocytose and degrade CaOx stone fragments while CaOx crystals induce M1 macrophages polarization and stimulate inflammatory responses in monocytes. Androgen receptor also influences macrophage differentiation by regulating macrophage colony-stimulating factor, polarizing monocytes, and naïve macrophages into anti-inflammatory macrophages.
Additionally, high oxalate can impact mitochondria of circulating monocytes, perhaps leading to altered macrophage polarization, promoting M1 over M2. Immune dysfunction in stone patients may involve oxalate and CaOx crystals mediated production of reactive oxygen species (ROS) within monocytes damaging their mitochondria and impairing stone crystal clearance.
In addition to oxidative stress, high oxalate and CaOx crystals can induce inflammatory responses through the activation of NLRP3 inflammasome, which triggers the release of proinflammatory cytokines IL-1B and IL-18. Inactivating NLRP3 may prevent oxalate-induced damage by altering macrophage polarization. It has been shown that antioxidant treatment of experimentally induced hyperoxaluria in rats leads to a reduction in the inflammatory responses and production of inflammatory molecules.
Despite the aforementioned knowledge, the immunity and inflammatory response in kidney stone disease remain unclear and need further elucidations This Research Topic aims at better understanding the pathogenic mechanisms of kidney stone disease and may also lead to a new hope to lessen the recurrent stone formation and complications.
In this Research Topic, we welcome Original Research, Reviews/Mini-reviews, Perspective, and Opinion articles focusing on any aspects of the immunity and inflammatory response in kidney stone disease. The themes that are covered include (but are not limited to):
- In vitro and in vivo studies of the immunity and inflammatory cascades related to kidney stone disease.
- Tissue, cellular and subcellular investigations of the kidney, interstitium as well as extracellular matrix at all stages of kidney stone disease-related immunity and inflammation.
- Roles of immune cells in kidney stone disease.
- Inflammasome and non-inflammasome mediated immune response related to kidney stone disease.
- Roles of cytokines/chemokines in kidney stone disease.
- Molecular trafficking and signal transduction involving inflammatory pathways in kidney stone disease.
- DNAs, RNAs, microRNAs, proteins, metabolites, macromolecules, chemicals, and other small molecules that mediate immunity and inflammatory response in kidney stone disease.
- Roles of ROS in immune response in kidney stone disease.
- Roles for renin-angiotensin-aldosterone system (RAAS) in kidney stone disease.
- Omics and technical advances to address the immunity and inflammatory cascades related to kidney stone formation.
- Therapeutic intervention of inflammation in kidney stone disease.
The development of RPs in the renal interstitium is considered as the first step in the development of the majority of idiopathic CaOx stones and cannot be accomplished simply through increased supersaturation of calcium and oxalate ions in the tubular fluid. It has been proposed that RP formation is similar to vascular calcification which is associated with the production of ROS, inflammation, and osteogenic changes.
Different studies indicate increased expression of genes related to inflammation, immunity, and complement activation pathways in the renal tissue of stone patients. Macrophages appear to be critically involved in this process. M1 related genes appear to be associated with the promotion of stone formation while M2 related genes with stone suppression. M2 macrophages phagocytose and degrade CaOx stone fragments while CaOx crystals induce M1 macrophages polarization and stimulate inflammatory responses in monocytes. Androgen receptor also influences macrophage differentiation by regulating macrophage colony-stimulating factor, polarizing monocytes, and naïve macrophages into anti-inflammatory macrophages.
Additionally, high oxalate can impact mitochondria of circulating monocytes, perhaps leading to altered macrophage polarization, promoting M1 over M2. Immune dysfunction in stone patients may involve oxalate and CaOx crystals mediated production of reactive oxygen species (ROS) within monocytes damaging their mitochondria and impairing stone crystal clearance.
In addition to oxidative stress, high oxalate and CaOx crystals can induce inflammatory responses through the activation of NLRP3 inflammasome, which triggers the release of proinflammatory cytokines IL-1B and IL-18. Inactivating NLRP3 may prevent oxalate-induced damage by altering macrophage polarization. It has been shown that antioxidant treatment of experimentally induced hyperoxaluria in rats leads to a reduction in the inflammatory responses and production of inflammatory molecules.
Despite the aforementioned knowledge, the immunity and inflammatory response in kidney stone disease remain unclear and need further elucidations This Research Topic aims at better understanding the pathogenic mechanisms of kidney stone disease and may also lead to a new hope to lessen the recurrent stone formation and complications.
In this Research Topic, we welcome Original Research, Reviews/Mini-reviews, Perspective, and Opinion articles focusing on any aspects of the immunity and inflammatory response in kidney stone disease. The themes that are covered include (but are not limited to):
- In vitro and in vivo studies of the immunity and inflammatory cascades related to kidney stone disease.
- Tissue, cellular and subcellular investigations of the kidney, interstitium as well as extracellular matrix at all stages of kidney stone disease-related immunity and inflammation.
- Roles of immune cells in kidney stone disease.
- Inflammasome and non-inflammasome mediated immune response related to kidney stone disease.
- Roles of cytokines/chemokines in kidney stone disease.
- Molecular trafficking and signal transduction involving inflammatory pathways in kidney stone disease.
- DNAs, RNAs, microRNAs, proteins, metabolites, macromolecules, chemicals, and other small molecules that mediate immunity and inflammatory response in kidney stone disease.
- Roles of ROS in immune response in kidney stone disease.
- Roles for renin-angiotensin-aldosterone system (RAAS) in kidney stone disease.
- Omics and technical advances to address the immunity and inflammatory cascades related to kidney stone formation.
- Therapeutic intervention of inflammation in kidney stone disease.
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