Role of inflammation and inflammasome activation in human bile cast nephropathy

Giuliani, K.; Kassianos, Andrew J.; Kildey, Katrina; Grivei, Anca; Wang, Xiangju; Ungerer, Jacobus; Francis, Leo; Healy, Helen; Gois, Pedro Henrique França

doi:10.1111/nep.13696

Cited by 5 publications

(2 citation statements)

References 21 publications

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“…As an antigen-presenting protein, CD1C can combine lipid and glycolipid antigens and submit them to T-cell receptors on NK-T cells to further activate the immune system (38). While CD1C is rarely expressed in normal kidneys, an increase in its expression has been significantly associated with renal interstitial immune cell infiltration and fibrosis (39,40). A member of the interleukin-1 family, IL33, can bind to IL1RL1/ ST2 receptors to activate the NF-κB and MAPK signaling pathways in Th2 cells, and induce the secretion of type 2-related cytokines in T-helper cells (41).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis identifies diagnostic biomarkers and their correlation with immune infiltration in diabetic nephropathy

et al. 2022

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Background: Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD). Currently, microalbuminuria is mainly used as a diagnostic indicator of DN, but there are still limitations and lack of immune-related diagnostic markers. In this study, we aimed to explore diagnostic biomarkers associated with immune infiltration of DN.Methods: Immune-related differentially expressed genes (DEGs) were derived from those at the intersection of the ImmPort database and DEGs identified from 3 datasets, which were based on the Gene Expression Omnibus (GEO). Functional enrichment analyses were performed; a protein-protein interaction (PPI) network was constructed; and hub genes were identified by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). After screening the key genes using least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE), a prediction model for DN was constructed. The predictive performance of the model was quantified by receiver-operating characteristic curve, decision curve analysis, and nomogram. Next, infiltration of 22 types of immune cells in DN kidney tissue was evaluated using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). Expression of diagnostic markers was analyzed in DN and control patient groups to determine the genes with the maximum diagnostic potential. Finally, we explored the correlation between diagnostic markers and immune cells.Results: Overall, 191 immune-related DEGs were identified, that primarily positively regulated with cell adhesion, T cell activation, leukocyte proliferation and migration, urogenital system development, lymphocyte differentiation and proliferation, and mononuclear cell proliferation. Gene sets were related to the PI3K-Akt, MAPK, Rap1, and WNT signaling pathways. Finally, CCL19, CD1C, and IL33 were identified as diagnostic markers of DN and recognized in the 3 datasets [area under the curve (AUC) =0.921]. Immune cell infiltration analysis demonstrated that CCL19 was positively correlated with macrophages M1 (R=0.47, P<0.001) and macrophages M2 (R=0.75, P<0.001). CD1C was positively correlated with macrophages M1 (R=0.47, P<0.05), macrophages M2 (R=0.75, P<0.01), and monocytes (R=0.42, P<0.01). IL33 was positively correlated with macrophages M1 (R=0.45, P<0.05), macrophages M2 (R=0.74, P<0.01), and monocytes (R=0.41, P<0.01).Conclusions: Our results provide evidence that CCL19, CD1C, and IL33, which are associated with immune infiltration, are the potential diagnostic biomarkers for DN candidates.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis identifies diagnostic biomarkers and their correlation with immune infiltration in diabetic nephropathy

et al. 2022

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“…Recent studies have considered the extra-hepatic effects of bile salts on the myocardium, where it was shown that elevated levels of bile salts elicited a negative inotropic and chronotropic effect leading to renal hypo-perfusion [2]. Interestingly, it has been suggested that bile casts may trigger the inflammasome signalling cascade via built up oxidative stress, hence leading to interstitial inflammation and driving bile cast nephropathy pathobiology [5]. Although kidney biopsy is the solitary means of establishing definitive diagnosis, it is often too invasive, or not practical.…”

Section: Discussionmentioning

confidence: 99%

Bile Cast Nephropathy an Important Biliary Culprit of Kidney Injury

Yusuf

Weissman

Qureshi

et al. 2021

Journal of Community Hospital Internal Medicine Perspectives

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Bile cast nephropathy (BCN) is a rare form of acute kidney injury (AKI) that occurs in the setting of hyperbilirubinemia. We present the case of a 67 year-old male with severe kidney injury who was found to have obstructive cholestasis. By way of this report, we aim to expand upon the existing literature and showcase the importance of timely endoscopic retrograde cholangio-pancreatography (ERCP) in this setting, in order to prevent irreversible kidney damage.

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Cholemic Nephropathy: Role in Acute Kidney Injury in Cholestasis and Cirrhosis

Pinter,

Rosenkranz

2024

Advances in Kidney Disease and Health

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Role of inflammation and inflammasome activation in human bile cast nephropathy

Cited by 5 publications

References 21 publications

Bioinformatics analysis identifies diagnostic biomarkers and their correlation with immune infiltration in diabetic nephropathy

Bioinformatics analysis identifies diagnostic biomarkers and their correlation with immune infiltration in diabetic nephropathy

Bile Cast Nephropathy an Important Biliary Culprit of Kidney Injury

Cholemic Nephropathy: Role in Acute Kidney Injury in Cholestasis and Cirrhosis

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