Role of Chemokine (C–X–C Motif) Ligand 10 (CXCL10) in Renal Diseases

Gao, Jie; Wu, Lingling; Wang, Siyang; Chen, Xiangmei

doi:10.1155/2020/6194864

Cited by 39 publications

(33 citation statements)

References 148 publications

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“…In normal condition, CXCL10 is expressed at low levels in the kidney, but their expression levels are upregulated in renal tubular cells after insult, involving in the pathogenesis of AKI [11,12,27]. Higher uCXCL10 levels were found among the critically ill children with AKI in our study, which was in consistent with a prospective nested case-control study performed by Ho J et al [17].…”

Section: Discussionsupporting

confidence: 91%

Urinary CXCL10 is Associated with Acute Kidney Injury and Sepsis, and Predicts Mortality in Critically Ill Children

Huang¹,

Zhou²,

Wang³

et al. 2020

Preprint

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Background: Acute kidney injury (AKI) biomarkers are often susceptible to confounding factors, limiting their utility as a specific biomarker, in the prediction of AKI, especially in heterogeneous population. The urinary CXC motif chemokine 10 (uCXCL10), as an inflammatory mediator, has been proposed to be a biomarker for AKI in a specific setting. Whether uCXCL10 is associated with AKI and predicts AKI in critically ill patients remains unclear. The aims of the study were to investigate clinical variables potentially associated with uCXCL10 levels and determine the associations of uCXCL10 with AKI, sepsis and PICU mortality in critically ill children, as well as its predictive values of aforementioned issues. Methods: Urinary CXCL10 levels were serially measured in a heterogeneous group of children during the first week after pediatric intensive care unit (PICU) admission. AKI diagnosis was based on the criteria of Kidney Disease: Improving Global Outcomes with serum creatinine and urine output. Sepsis was diagnosed according to surviving sepsis campaign international guidelines for children. Mortality was defined as all-cause death occurring during the PICU stay.Results: Among 342 critically ill children, 52 (15.2%) developed AKI during the first week after PICU admission, and 132 (38.6%) were diagnosed as sepsis and 30 (12.3%) died during PICU stay. Both the initial and peak values of uCXCL10 remained independently associated with AKI with adjusted odds ratios (AORs) of 1.791 (P = 0.010) and 2.002 (P = 0.002), sepsis with AORs of 1.679 (P = 0.003) and 1.752 (P = 0.002), septic AKI with AORs of 3.281 (P <0.001) and 3.172 (P <0.001), and PICU mortality with AORs of 2.779 (P = 0.001) and 3.965 (P <0.001), respectively. The AUCs of the initial uCXCL10 for predicting AKI, sepsis, septic AKI, and PICU mortality were 0.63 (0.53-0.72), 0.62 (0.56-0.68), 0.75 (0.64-0.87), and 0.77 (0.68-0.86), respectively. The AUCs for prediction by using peak uCXCL10 were as follows: AKI 0.65 (0.56-0.75), sepsis 0.63 (0.57-0.69), septic AKI 0.76 (0.65-0.87), and PICU mortality 0.84 (0.76-0.91).Conclusions: Urinary CXCL10 is independently associated with AKI and sepsis, and may be a potential indicator of septic AKI and PICU mortality in critically ill children.

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Section: Discussionsupporting

confidence: 91%

Urinary CXCL10 is Associated with Acute Kidney Injury and Sepsis, and Predicts Mortality in Critically Ill Children

Huang¹,

Zhou²,

Wang³

et al. 2020

Preprint

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“…To the best of our knowledge, no other studies have been performed except our previous study on serum NGAL [ 43 ]. Therefore, we aimed to evaluate the diagnostic value of the serum concentrations of biomarkers whose urine concentrations have exhibited promising results for detection of VIKI (osteopontin, NGAL, clusterin) or other drug-induced kidney injury (TFF3) and those that have shown to reflect renal tubular injury (CXCL10, IL-18, TNF-R1, osteopontin, RBP4, and cystatin C) for the diagnosis of VIKI [ 37 , 39 , 44 ]. In our study, serum TFF3, cystatin C, TNF-R1, and osteopontin showed the best diagnostic value for VIKI.…”

Section: Discussionmentioning

confidence: 99%

“…Based on experimental animal model studies, VIKI is suggested to be associated with oxidative stress caused by reabsorbed vancomycin accumulated in the lysosomes of proximal tubular cells [ 12 , 35 , 36 ]. Therefore, the biomarkers shown to reflect tubular injury in previous publications were also evaluated, such as cystatin C, tumor necrosis factor receptor 1 (TNF-R1), interleukin-18 (IL-18), C-X-C motif chemokine ligand 10 (CXCL10), osteopontin, and retinol binding protein 4 (RBP4) [ 37 , 38 , 39 ]. Here, we aim to identify candidate serum biomarkers for the diagnosis of VIKI.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Value of Multiple Serum Biomarkers for Vancomycin-Induced Kidney Injury

Kim

Lee

Kim

et al. 2021

JCM

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Acute kidney injury (AKI) is a major contributor to in-hospital morbidity and mortality. Vancomycin, one of the most commonly used antibiotics in a clinical setting, is associated with AKI, with its incidence ranging up to 43%. Despite the high demand, few studies have investigated serum biomarkers to detect vancomycin-induced kidney injury (VIKI). Here, we evaluated the diagnostic value of nine candidate serum biomarkers for VIKI. A total of 23,182 cases referred for vancomycin concentration measurement from January 2018 to December 2019 were screened and 28 subjects with confirmed VIKI were enrolled (VIKI group). Age- and sex- matched control group consisted of 21 subjects who underwent vancomycin therapy without developing VIKI (non-VIKI group), and 23 healthy controls (HC group). The serum concentrations of clusterin, retinol binding protein 4 (RBP4), interleukin-18 (IL-18), tumor necrosis factor receptor 1 (TNF-R1), C-X-C motif chemokine ligand 10 (CXCL10), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, trefoil factor-3 (TFF3), and cystatin C were compared among the three groups, and their correlations with estimated glomerular filtration rate (eGFR) and diagnostic values for VIKI were assessed. All of the biomarkers except clusterin and RBP4 exhibited significant elevation in the VIKI group. Serum TFF3, cystatin C, TNF-R1, and osteopontin demonstrated an excellent diagnostic value for VIKI (TFF3, area under the curve (AUC) 0.932; cystatin C, AUC 0.917; TNF-R1, AUC 0.866; osteopontin, AUC 0.787); and except osteopontin, a strong negative correlation with eGFR (TFF3, r = −0.71; cystatin C, r = −0.70; TNF-R1, r = −0.60). IL-18, CXCL10, and NGAL showed weak correlation with eGFR and moderate diagnostic value for VIKI. This study tested multiple serum biomarkers for VIKI and showed that serum TFF3, cystatin C, TNF-R1, and osteopontin could efficiently discriminate VIKI patients. Further studies are warranted to clarify the diagnostic value of these biomarkers in VIKI.

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“…To demonstrate the anti-inflammatory and anti-fibrosis therapeutic efficacy, we evaluated the therapeutic effects of DXMS/CAP@PLGA-ILs in a mouse model of mesangial proliferative glomerulonephritis (MesPGN), the most common pathological form of GN, which is characterized by MC proliferation and mesangial matrix accumulation, and inflammation-related cytokines play an important role in its pathology. 30 , 31 Habu snake venom (HSV) was used to induce the mouse model of MesPGN. 32 , 33 To improve the success rate of modeling, HSV was injected twice through the caudal vein.…”

Section: Methodsmentioning

confidence: 99%

Co-Delivery of Dexamethasone and Captopril by α8 Integrin Antibodies Modified Liposome-PLGA Nanoparticle Hybrids for Targeted Anti-Inflammatory/Anti-Fibrosis Therapy of Glomerulonephritis

Zhou

Zhang³

et al. 2022

IJN

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Purpose Mesangial cells-mediated glomerulonephritis refers to a category of immunologically mediated glomerular injuries characterized by infiltration of circulating inflammatory cells, proliferation of mesangial cells, and the common pathological manifestation to the later stage is renal fibrosis, accompanied by excessive accumulation of extracellular matrix (ECM). Treatment regimens include glucocorticoids and immunosuppressive agents, but their off-target distribution causes severe systemic toxicity. Hence, specific co-delivery of “anti-inflammatory/anti-fibrosis” drugs to the glomerular mesangial cell (MC) region is expected to produce better therapeutic effects. Methods A novel kidney-targeted nanocarrier drug delivery system targeting MCs was constructed using passive targeting resulting from the difference in pore size between the glomerular endothelial layer and the basement membrane, and active targeting based on the specific binding of antibodies and antigens. Specifically, a liposome-nanoparticle hybrid (PLGA-LNHy) was formed by coating the surface of PLGA nanoparticles (NPs) with a phospholipid bilayer, and then PLGA-LNHy was co-modified with PEG and α8 integrin antibodies to obtain PLGA immunoliposomes (PLGA-ILs). Results The results showed that the obtained NPs had a core-shell structure, uniform and suitable particle size (119.1 ± 2.31 nm), low cytotoxicity, and good mesangial cell-entry ability, which can successfully accumulate in the glomerular MC region. Both dexamethasone (DXMS) and captopril (CAP) were loaded onto PLGA-ILs with a drug loading of 10.22 ± 1.00% for DXMS and 6.37 ± 0.25% for CAP (DXMS/CAP@PLGA-ILs). In vivo pharmacodynamics showed that DXMS/CAP@PLGA-ILs can effectively improve the pathological changes in the mesangial area and positive expression of proliferating cell nuclear antigen (PCNA) in glomeruli as well as reduce the expression of inflammatory factors, fibrotic factors and reactive oxygen species (ROS). Thus, renal inflammation and fibrosis were relieved. Conclusion We have provided a strategy to increase nanoparticle accumulation in MCs with the potential to implement regulatory effects of anti-inflammatory and anti-fibrosis in glomerulonephritis (GN).

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Role of Chemokine (C–X–C Motif) Ligand 10 (CXCL10) in Renal Diseases

Cited by 39 publications

References 148 publications

Urinary CXCL10 is Associated with Acute Kidney Injury and Sepsis, and Predicts Mortality in Critically Ill Children

Urinary CXCL10 is Associated with Acute Kidney Injury and Sepsis, and Predicts Mortality in Critically Ill Children

Diagnostic Value of Multiple Serum Biomarkers for Vancomycin-Induced Kidney Injury

Co-Delivery of Dexamethasone and Captopril by α8 Integrin Antibodies Modified Liposome-PLGA Nanoparticle Hybrids for Targeted Anti-Inflammatory/Anti-Fibrosis Therapy of Glomerulonephritis

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