cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.26555164.v1
title: Risk factors for unplanned weaning of continuous renal replacement therapy in ICU patients: a meta-analysis

description: To systematically review the risk factors for unplanned weaning during continuous renal replacement therapy in ICU patients. A combination of subject words + free words was used to search the relevant literature published in CNKI, Wanfang, VIP, CBM, PubMed, EMbase, Web of Science, Cochrane Library, Mediline and other databases. The search period was from the establishment of the databases to June 25, 2024. Revman 5.4 software and Stata15.0 software was used to meta-analyze the risk factors for unplanned weaning during continuous renal replacement therapy in ICU patients. A total of 23 studies were included in this meta-analysis, describing 15 variables, 3793 patients, and using 7197 filters. Meta-analysis results showed that risk factors for unplanned weaning during continuous renal replacement therapy in ICU patients were as follows: Low mean arterial pressure [OR = 1.02, 95%CI (1.00, 1.03), <i>p</i> &lt; 0.05], hypothermia [OR = 3.40, 95%CI (1.78, 6.47), <i>p</i> &lt; 0.05], age (≥60 years) [OR = 4.45, 95%CI (3.18, 6.22), <i>p</i> &lt; 0.05], comorbid underlying disease [OR = 3.63, 95%CI (2.70, 4.88), <i>p</i> &lt; 0.05], agitation [OR = 4.97, 95%CI (3.20, 7.74), <i>p</i> &lt; 0.05], no anticoagulant use [OR = 1.65, 95%CI (1.25, 2.17), <i>p</i> &lt; 0.05], short activated partial prothrombin time [OR = 1.23, 95%CI (1.13, 1.34), <i>p</i> &lt; 0.05], hyper-hematocrit [OR = 1.73, 95%CI (1.13, 2.66), <i>p</i> = 0.01], low ionized calcium concentration [OR = 1.48, 95% CI (1.08, 2.02), <i>p</i> = 0.01], CRRT that was treated at a high dose [OR = 1.42, 95%CI (1.14, 1.76), <i>p</i> &lt; 0.05], mechanical ventilation [OR = 4.25, 95%CI (2.67, 6.77), <i>p</i> &lt; 0.05], and lack of dedicated care [OR = 5.08, 95%CI (2.51, 10.28), <i>p</i> &lt; 0.05]. However, it is unclear whether platelet count, prothrombin activity, and blood flow velocity are risk factors for unplanned weaning during CRRT in ICU patients, and more studies are needed for further validation. Available evidence suggests that a variety of factors contribute to unplanned weaning of CRRT in ICU patients. Early detection of these risk factors is essential for healthcare professionals to develop preventive and curative strategies. This study is registered on the PROSERO website under registration number CRD42024543554.
DOI: 10.6084/m9.figshare.27088795
title: <i>EIF2AK2</i> protein targeted activation of <i>AIM2</i>-mediated PANoptosis promotes sepsis-induced acute kidney injury

description: Acute kidney injury (AKI) frequently occurs as a complication of sepsis. PANoptosis refers to a type of inflammatory programmed cell death that exhibits key characteristics of apoptosis, necroptosis, and pyroptosis. Here, we evaluated the role of absent in melanoma 2 (AIM2) and eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) in septic AKI. A septic AKI model was created through cecal ligation and puncture (CLP), while an <i>in vitro</i> model was developed using lipopolysaccharide (LPS)-stimulated HK2 cells. Hematoxylin and eosin (HE), Periodic acid-Schiff (PAS), and TUNEL staining were conducted to assess kidney injury in mice. Levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were detected by kits. Gene expression was detected utilizing RT-qPCR, and Western blot was used to test protein levels. Immunofluorescence was employed to measure EIF2AK2 and AIM2 expression in mouse kidney tissue. Lactate dehydrogenase (LDH) activity assay was conducted to evaluate cytotoxicity. Co-immunoprecipitation (Co-IP) was performed to verify the binding relationship between EIF2AK2 and AIM2. AIM2 expression was increased in the renal tissue of mice subjected to CLP. Activation of the inflammasome and PANoptosis were observed in the renal tissue of CLP mice. AIM2 depletion attenuated PANoptosis in LPS-treated HK-2 cells. Additionally, EIF2AK2 could directly target AIM2, leading to a positive regulation of AIM2 expression. Notably, EIF2AK2 induced PANoptosis through upregulating AIM2 in HK-2 cells stimulated by LPS. Our results revealed the important role of EIF2AK2-induced AIM2 upregulation in the activation of PANoptosis during septic AKI. Renal tissue from CLP mice exhibited an increase in AIM2 expression.Renal tissue from CLP mice demonstrated inflammasome activation and PANoptosis.AIM2 silencing reduced PANoptosis in LPS-treated HK-2 cells.EIF2AK2 directly targeted AIM2 and positively regulated its expression.EIF2AK2 promoted PANoptosis via AIM2 in LPS-triggered HK-2 cells. Renal tissue from CLP mice exhibited an increase in AIM2 expression. Renal tissue from CLP mice demonstrated inflammasome activation and PANoptosis. AIM2 silencing reduced PANoptosis in LPS-treated HK-2 cells. EIF2AK2 directly targeted AIM2 and positively regulated its expression. EIF2AK2 promoted PANoptosis via AIM2 in LPS-triggered HK-2 cells.
DOI: 10.6084/m9.figshare.27088795.v1
title: <i>EIF2AK2</i> protein targeted activation of <i>AIM2</i>-mediated PANoptosis promotes sepsis-induced acute kidney injury

description: Acute kidney injury (AKI) frequently occurs as a complication of sepsis. PANoptosis refers to a type of inflammatory programmed cell death that exhibits key characteristics of apoptosis, necroptosis, and pyroptosis. Here, we evaluated the role of absent in melanoma 2 (AIM2) and eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) in septic AKI. A septic AKI model was created through cecal ligation and puncture (CLP), while an <i>in vitro</i> model was developed using lipopolysaccharide (LPS)-stimulated HK2 cells. Hematoxylin and eosin (HE), Periodic acid-Schiff (PAS), and TUNEL staining were conducted to assess kidney injury in mice. Levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were detected by kits. Gene expression was detected utilizing RT-qPCR, and Western blot was used to test protein levels. Immunofluorescence was employed to measure EIF2AK2 and AIM2 expression in mouse kidney tissue. Lactate dehydrogenase (LDH) activity assay was conducted to evaluate cytotoxicity. Co-immunoprecipitation (Co-IP) was performed to verify the binding relationship between EIF2AK2 and AIM2. AIM2 expression was increased in the renal tissue of mice subjected to CLP. Activation of the inflammasome and PANoptosis were observed in the renal tissue of CLP mice. AIM2 depletion attenuated PANoptosis in LPS-treated HK-2 cells. Additionally, EIF2AK2 could directly target AIM2, leading to a positive regulation of AIM2 expression. Notably, EIF2AK2 induced PANoptosis through upregulating AIM2 in HK-2 cells stimulated by LPS. Our results revealed the important role of EIF2AK2-induced AIM2 upregulation in the activation of PANoptosis during septic AKI. Renal tissue from CLP mice exhibited an increase in AIM2 expression.Renal tissue from CLP mice demonstrated inflammasome activation and PANoptosis.AIM2 silencing reduced PANoptosis in LPS-treated HK-2 cells.EIF2AK2 directly targeted AIM2 and positively regulated its expression.EIF2AK2 promoted PANoptosis via AIM2 in LPS-triggered HK-2 cells. Renal tissue from CLP mice exhibited an increase in AIM2 expression. Renal tissue from CLP mice demonstrated inflammasome activation and PANoptosis. AIM2 silencing reduced PANoptosis in LPS-treated HK-2 cells. EIF2AK2 directly targeted AIM2 and positively regulated its expression. EIF2AK2 promoted PANoptosis via AIM2 in LPS-triggered HK-2 cells.
DOI: 10.6084/m9.figshare.27188614
title: Identification of serum biomarkers for chronic kidney disease using serum metabolomics

description: This study aimed to identify biomarkers for chronic kidney disease (CKD) by studying serum metabolomics. Serum samples were collected from 194 non-dialysis CKD patients and 317 healthy controls (HC). Using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS), untargeted metabolomics analysis was conducted. A random forest model was developed and validated in separate sets of HC and CKD patients. The serum metabolomic profiles of patients with chronic kidney disease (CKD) exhibited significant differences compared to healthy controls (HC). A total of 314 metabolites were identified as significantly different, with 179 being upregulated and 135 being downregulated in CKD patients. KEGG enrichment analysis revealed several key pathways, including arginine biosynthesis, phenylalanine metabolism, linoleic acid metabolism, and purine metabolism. The diagnostic efficacy of the classifier was high, with an area under the curve of 1 in the training and validation sets and 0.9435 in the cross-validation set. This study provides comprehensive insights into serum metabolism in non-dialysis CKD patients, highlighting the potential involvement of abnormal biological metabolism in CKD pathogenesis. Exploring metabolites may offer new possibilities for the management of CKD.
DOI: 10.6084/m9.figshare.27188614.v1
title: Identification of serum biomarkers for chronic kidney disease using serum metabolomics

description: This study aimed to identify biomarkers for chronic kidney disease (CKD) by studying serum metabolomics. Serum samples were collected from 194 non-dialysis CKD patients and 317 healthy controls (HC). Using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS), untargeted metabolomics analysis was conducted. A random forest model was developed and validated in separate sets of HC and CKD patients. The serum metabolomic profiles of patients with chronic kidney disease (CKD) exhibited significant differences compared to healthy controls (HC). A total of 314 metabolites were identified as significantly different, with 179 being upregulated and 135 being downregulated in CKD patients. KEGG enrichment analysis revealed several key pathways, including arginine biosynthesis, phenylalanine metabolism, linoleic acid metabolism, and purine metabolism. The diagnostic efficacy of the classifier was high, with an area under the curve of 1 in the training and validation sets and 0.9435 in the cross-validation set. This study provides comprehensive insights into serum metabolism in non-dialysis CKD patients, highlighting the potential involvement of abnormal biological metabolism in CKD pathogenesis. Exploring metabolites may offer new possibilities for the management of CKD.
DOI: 10.6084/m9.figshare.26346750
title: Elucidating the causal nexus and immune mediation between frailty and chronic kidney disease: integrative multi-omics analysis

description: Empirical research has consistently documented the concurrent manifestation of frailty and chronic kidney disease (CKD). However, the existence of a reverse causal association or the influence of confounding variables on these correlations remains ambiguous. Our analysis of 7,078 participants from National Health and Nutrition Examination Survey(NHANES) (1999–2018) applied weighted logistic regression and Mendelian Randomization (MR) to investigate the correlation between the frailty index (FI) and renal function. The multivariate MR analysis was specifically adjusted for type 2 diabetes and hypertension. Further analysis explored 3282 plasma proteins to link FI to CKD. A two-step network MR highlighted immune cells’ mediating roles in the FI-CKD relationship Genetically inferred FI and various renal function markers are significantly correlated, as supported by NHANES analyses. Multivariate MR analysis revealed a direct causal association between the FI and CKD. Additionally, our investigation into plasma proteins identified Tmprss11D and MICB correlated with FI and CKD, respectively. A two-step network MR to reveal 15 immune cell types, notably Central Memory CD4+ T cells and Lymphocytes, as crucial mediators between FI and CKD. Our work establishes a causal connection between frailty and CKD, mediated by specific immune cell profiles. These findings highlight the importance of immune mechanisms in the frailty-CKD interplay and suggest that targeting shared risk factors and immune pathways could improve management strategies for these conditions. Our research contributes to a more nuanced understanding of frailty and CKD, offering new avenues for intervention and patient care in an aging population.
DOI: 10.6084/m9.figshare.26346750.v1
title: Elucidating the causal nexus and immune mediation between frailty and chronic kidney disease: integrative multi-omics analysis

description: Empirical research has consistently documented the concurrent manifestation of frailty and chronic kidney disease (CKD). However, the existence of a reverse causal association or the influence of confounding variables on these correlations remains ambiguous. Our analysis of 7,078 participants from National Health and Nutrition Examination Survey(NHANES) (1999–2018) applied weighted logistic regression and Mendelian Randomization (MR) to investigate the correlation between the frailty index (FI) and renal function. The multivariate MR analysis was specifically adjusted for type 2 diabetes and hypertension. Further analysis explored 3282 plasma proteins to link FI to CKD. A two-step network MR highlighted immune cells’ mediating roles in the FI-CKD relationship Genetically inferred FI and various renal function markers are significantly correlated, as supported by NHANES analyses. Multivariate MR analysis revealed a direct causal association between the FI and CKD. Additionally, our investigation into plasma proteins identified Tmprss11D and MICB correlated with FI and CKD, respectively. A two-step network MR to reveal 15 immune cell types, notably Central Memory CD4+ T cells and Lymphocytes, as crucial mediators between FI and CKD. Our work establishes a causal connection between frailty and CKD, mediated by specific immune cell profiles. These findings highlight the importance of immune mechanisms in the frailty-CKD interplay and suggest that targeting shared risk factors and immune pathways could improve management strategies for these conditions. Our research contributes to a more nuanced understanding of frailty and CKD, offering new avenues for intervention and patient care in an aging population.
DOI: 10.6084/m9.figshare.28244073
title: Effects of resistant starch supplementation on renal function and inflammatory markers in patients with chronic kidney disease: a meta-analysis of randomized controlled trials

description: Recent studies have shown that consumption of resistant starch (RS) has beneficial effects on the gut microbiota and immune function in patients with chronic kidney disease (CKD). The objective of this study was to evaluate the effects of RS on inflammation, uremic toxins, and renal function in patients with CKD through a systematic review and meta-analysis. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-2020. We included randomized controlled trials comparing RS supplementation to placebo. The National Library of Medicine (PubMed), Excerpta Medica Database (Embase), Cochrane Library, Web of Science, China National Knowledge Internet (CNKI) databases, and two gray literature sources – Baidu and Research Gate, were used for search, up to 28 August 2024. There was no limitation on publication date, but only manuscripts published in English and Chinese were included. A total of 645 articles were retrieved. Ten articles met the inclusion criteria, and a total of 355 subjects were included. The analysis revealed that RS dietary intervention can significantly reduce indoxyl sulfate (IS) levels (SMD: −0.37, 95% confidence interval (CI): −0.70 to −0.04, <i>p</i> = .03) and blood urea nitrogen (BUN) levels (SMD: −0.30, 95% CI: −0.57 to −0.02, <i>p</i> = .03). There were no significant differences in the levels of interleukin-6 (IL-6), p-cresyl sulfate (p-CS), albumin, phosphorus, or tumor necrosis factor-α. The RS diet has potential beneficial effects on uremic toxin levels and renal function indices in patients with CKD. RS supplementation can reduce uremic toxin levels and improve renal function but does not reduce the inflammatory response in patients with CKD. Nevertheless, results should be cautiously interpreted, because of the limited sample size and different treatment dosages. Further research is necessary to corroborate the beneficial effects of RS2 supplementation in this population.
DOI: 10.6084/m9.figshare.28244073.v1
title: Effects of resistant starch supplementation on renal function and inflammatory markers in patients with chronic kidney disease: a meta-analysis of randomized controlled trials

description: Recent studies have shown that consumption of resistant starch (RS) has beneficial effects on the gut microbiota and immune function in patients with chronic kidney disease (CKD). The objective of this study was to evaluate the effects of RS on inflammation, uremic toxins, and renal function in patients with CKD through a systematic review and meta-analysis. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-2020. We included randomized controlled trials comparing RS supplementation to placebo. The National Library of Medicine (PubMed), Excerpta Medica Database (Embase), Cochrane Library, Web of Science, China National Knowledge Internet (CNKI) databases, and two gray literature sources – Baidu and Research Gate, were used for search, up to 28 August 2024. There was no limitation on publication date, but only manuscripts published in English and Chinese were included. A total of 645 articles were retrieved. Ten articles met the inclusion criteria, and a total of 355 subjects were included. The analysis revealed that RS dietary intervention can significantly reduce indoxyl sulfate (IS) levels (SMD: −0.37, 95% confidence interval (CI): −0.70 to −0.04, <i>p</i> = .03) and blood urea nitrogen (BUN) levels (SMD: −0.30, 95% CI: −0.57 to −0.02, <i>p</i> = .03). There were no significant differences in the levels of interleukin-6 (IL-6), p-cresyl sulfate (p-CS), albumin, phosphorus, or tumor necrosis factor-α. The RS diet has potential beneficial effects on uremic toxin levels and renal function indices in patients with CKD. RS supplementation can reduce uremic toxin levels and improve renal function but does not reduce the inflammatory response in patients with CKD. Nevertheless, results should be cautiously interpreted, because of the limited sample size and different treatment dosages. Further research is necessary to corroborate the beneficial effects of RS2 supplementation in this population.
DOI: 10.6084/m9.figshare.28244076
title: Circulating RAC1 contributed to steroid-sensitive nephrotic syndrome: Mendelian randomization, single-cell RNA-sequencing, proteomic, and experimental evidence

description: The small GTPase Rac1 (RAC1) has been linked to podocyte disorders and steroid-sensitive nephrotic syndrome (SSNS). The aim of this study was to explore and validate the potential causal association between circulating RAC1 and SSNS. The association between circulating RAC1 and SSNS at both gene expression and proteomic levels was investigated using Mendelian randomization analysis, and further validated by single-cell RNA-sequencing, proteomic analysis, and experimental studies. The genetic instruments comprised cis-expression quantitative trait loci (cis-eQTLs) associated with <i>RAC1</i> gene expression and protein QTLs correlated with plasma RAC1 protein levels. Causal associations were estimated utilizing the inverse variance weighted and MR-PRESSO methods. Validation of <i>RAC1</i> expression was conducted through single-cell RNA-sequencing of peripheral blood mononuclear cells from patients with SSNS and healthy controls. Proteomic analysis was performed among patients with minimal change nephrotic syndrome. Experimental validation was conducted using a puromycin aminonucleoside (PAN)-induced nephrosis model. Increased expression of <i>RAC1</i> was associated with a higher risk of SSNS (gene expression level: odds ratio [OR], 1.53; 95% confidence interval [CI], 1.02–2.28; protein level: OR, 1.82; 95% CI, 1.05–3.17). The results of MR-PRESSO were consistent (gene expression level: OR, 1.49; 95% CI, 1.17–1.92; protein level: OR, 1.81; 95% CI, 1.16–2.85). Single-cell RNA sequencing and proteomic analysis confirmed elevated <i>RAC1</i> expression in patients with SSNS compared to healthy controls. Experimental data further supported increased <i>RAC1</i> expression in PAN-induced nephropathy. Increased expression of <i>RAC1</i> might be causally associated with SSNS, suggesting that targeting RAC1 might represent a potential therapeutic strategy for SSNS.
DOI: 10.6084/m9.figshare.28244076.v1
title: Circulating RAC1 contributed to steroid-sensitive nephrotic syndrome: Mendelian randomization, single-cell RNA-sequencing, proteomic, and experimental evidence

description: The small GTPase Rac1 (RAC1) has been linked to podocyte disorders and steroid-sensitive nephrotic syndrome (SSNS). The aim of this study was to explore and validate the potential causal association between circulating RAC1 and SSNS. The association between circulating RAC1 and SSNS at both gene expression and proteomic levels was investigated using Mendelian randomization analysis, and further validated by single-cell RNA-sequencing, proteomic analysis, and experimental studies. The genetic instruments comprised cis-expression quantitative trait loci (cis-eQTLs) associated with <i>RAC1</i> gene expression and protein QTLs correlated with plasma RAC1 protein levels. Causal associations were estimated utilizing the inverse variance weighted and MR-PRESSO methods. Validation of <i>RAC1</i> expression was conducted through single-cell RNA-sequencing of peripheral blood mononuclear cells from patients with SSNS and healthy controls. Proteomic analysis was performed among patients with minimal change nephrotic syndrome. Experimental validation was conducted using a puromycin aminonucleoside (PAN)-induced nephrosis model. Increased expression of <i>RAC1</i> was associated with a higher risk of SSNS (gene expression level: odds ratio [OR], 1.53; 95% confidence interval [CI], 1.02–2.28; protein level: OR, 1.82; 95% CI, 1.05–3.17). The results of MR-PRESSO were consistent (gene expression level: OR, 1.49; 95% CI, 1.17–1.92; protein level: OR, 1.81; 95% CI, 1.16–2.85). Single-cell RNA sequencing and proteomic analysis confirmed elevated <i>RAC1</i> expression in patients with SSNS compared to healthy controls. Experimental data further supported increased <i>RAC1</i> expression in PAN-induced nephropathy. Increased expression of <i>RAC1</i> might be causally associated with SSNS, suggesting that targeting RAC1 might represent a potential therapeutic strategy for SSNS.