cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.27145671.v1
title: The relationship between serum uric acid and gastrointestinal bleeding in peritoneal dialysis patients: a propensity score analysis

description: Gastrointestinal bleeding is an important gastrointestinal complication among peritoneal dialysis patients and correlated with a higher risk of mortality. Increased uric acid levels are a significant complication for peritoneal dialysis patients and have been associated with an increased risk of hemorrhagic stroke. The objective of the present study was to investigate the relationship between serum uric acid levels and gastrointestinal bleeding in peritoneal dialysis patients. A total of 2498 peritoneal dialysis patients were recruited. Based on the optimal uric acid cutoff value, two groups of patients were divided. We constructed a propensity-score-matched population of 1762 patients by matching sex, age, and body mass index. Survival outcomes between the two groups were compared using adjusted Kaplan–Meier curves. We constructed the restricted cubic splines regression to assess the correlation between levels of uric acid and gastrointestinal bleeding. A multivariate Cox proportional hazards regression was performed to test whether higher levels of uric acid are an independent risk factor for gastrointestinal bleeding. We performed a forest plot to show interaction effects in different subgroups. According to restricted cubic splines regression, uric acid levels were positively correlated with the risk of gastrointestinal bleeding events. After adjusted different confounding factors, patients with high levels of uric acid were prone to experience gastrointestinal bleeding (HR 1.868, 95%CI 1.001–3.486). In subgroups, the interaction between higher levels of uric acid and utilizing proton pump inhibitors was significant (P for interaction = 0.034). Further research found that taking proton pump inhibitors could decrease the risk of gastrointestinal bleeding in peritoneal dialysis patients accompanied high levels of uric acid. The baseline high levels of uric acid are an independent risk factor for gastrointestinal bleeding in patients undergoing peritoneal dialysis.
DOI: 10.6084/m9.figshare.27317264.v1
title: Association between albumin-corrected anion gap and kidney function in individuals with hypertension – NHANES 2009–2016 cycle

description: Long-term uncontrolled hypertension increases the risk of kidney decompensation. This study aimed to explore the connection between albumin-corrected anion gap (ACAG) and kidney function in hypertensive patients. This study utilized data from 1988 participants diagnosed with hypertension sourced from the NHANES database. Binary logistic regression analysis and subgroup analysis were utilized to investigate the relationship between ACAG and kidney function. The study employed restricted cubic spline (RCS) to assess the non-linear associations between ACAG and eGFR, as well as ACAG and ACR. Furthermore, mediation and moderation effect analyses were carried out, with blood pressure serving as the mediator and moderator, ACAG as the independent variable, and eGFR and ACR as the dependent variables. Finally, the study developed ACAG-based models for predicting kidney function decline. Higher ACAG is identified as an independent risk factor for eGFR &lt; 60 mL/minute/1.73 m<sup>2</sup> and ACR ≥ 30 mg/g. Results from RCS indicate a non-linear relationship between ACAG and eGFR, as well as between ACAG and ACR. The mediation effect analysis revealed that DBP mediated the relationship between ACAG and eGFR. Analysis on moderation effect demonstrated that SBP played a significant role in moderating the interaction between ACAG and ACR. Moreover, the models based on ACAG showed strong performance. The levels of ACAG are found to be independently associated with both eGFR and ACR. Additionally, ACAG shows promise as a new and dependable biomarker for predicting the decline in kidney function in hypertensive patients.
DOI: 10.6084/m9.figshare.27152679
title: Integrin subunit beta 6 is a potential diagnostic marker for acute kidney injury in patients with diabetic kidney disease: a single cell sequencing data analysis

description: Diabetic kidney disease (DKD), a prevalent complication of diabetes mellitus, is often associated with acute kidney injury (AKI). Thus, the development of preventive and therapeutic strategies is crucial for delaying the progression of AKI and DKD. The GSE183276 dataset, comprising the data of 20 healthy controls and 12 patients with AKI, was downloaded from the Gene Expression Omnibus (GEO) database to analyze the AKI group. For analyzing the DKD group, the GSE131822 dataset, comprising the data of 3 healthy controls and 3 patients with DKD, was downloaded from the GEO database. The common differentially expressed genes (DEGs) in renal tubular epithelial cells (TECs) were subjected to enrichment analyses. Next, a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes database to analyze gene-related regulatory networks. Finally, the AKI animal models and the DKD and AKI cell models were established, and the reliability of the identified genes was validated using quantitative real-time polymerase chain reaction analysis. Functional analysis was performed with 40 common DEGs in TECs. Eight hub genes were identified using the PPI and gene-related networks. Finally, validation experiments with the <i>in vivo</i> animal model and the <i>in vitro</i> cellular model revealed the four common DEGs. Four DEGs that share molecular mechanisms in the pathogenesis of DKD and AKI were identified. In particular, the expression of Integrin Subunit Beta 6(<i>ITGB6)</i>, a hub and commonly upregulated gene, was upregulated in the <i>in vitro</i> models. <i>ITGB6</i> may serve as a biomarker for early AKI diagnosis in patients with DKD and as a target for early intervention therapies.
DOI: 10.6084/m9.figshare.27152679.v1
title: Integrin subunit beta 6 is a potential diagnostic marker for acute kidney injury in patients with diabetic kidney disease: a single cell sequencing data analysis

description: Diabetic kidney disease (DKD), a prevalent complication of diabetes mellitus, is often associated with acute kidney injury (AKI). Thus, the development of preventive and therapeutic strategies is crucial for delaying the progression of AKI and DKD. The GSE183276 dataset, comprising the data of 20 healthy controls and 12 patients with AKI, was downloaded from the Gene Expression Omnibus (GEO) database to analyze the AKI group. For analyzing the DKD group, the GSE131822 dataset, comprising the data of 3 healthy controls and 3 patients with DKD, was downloaded from the GEO database. The common differentially expressed genes (DEGs) in renal tubular epithelial cells (TECs) were subjected to enrichment analyses. Next, a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes database to analyze gene-related regulatory networks. Finally, the AKI animal models and the DKD and AKI cell models were established, and the reliability of the identified genes was validated using quantitative real-time polymerase chain reaction analysis. Functional analysis was performed with 40 common DEGs in TECs. Eight hub genes were identified using the PPI and gene-related networks. Finally, validation experiments with the <i>in vivo</i> animal model and the <i>in vitro</i> cellular model revealed the four common DEGs. Four DEGs that share molecular mechanisms in the pathogenesis of DKD and AKI were identified. In particular, the expression of Integrin Subunit Beta 6(<i>ITGB6)</i>, a hub and commonly upregulated gene, was upregulated in the <i>in vitro</i> models. <i>ITGB6</i> may serve as a biomarker for early AKI diagnosis in patients with DKD and as a target for early intervention therapies.
DOI: 10.6084/m9.figshare.27317264
title: Association between albumin-corrected anion gap and kidney function in individuals with hypertension – NHANES 2009–2016 cycle

description: Long-term uncontrolled hypertension increases the risk of kidney decompensation. This study aimed to explore the connection between albumin-corrected anion gap (ACAG) and kidney function in hypertensive patients. This study utilized data from 1988 participants diagnosed with hypertension sourced from the NHANES database. Binary logistic regression analysis and subgroup analysis were utilized to investigate the relationship between ACAG and kidney function. The study employed restricted cubic spline (RCS) to assess the non-linear associations between ACAG and eGFR, as well as ACAG and ACR. Furthermore, mediation and moderation effect analyses were carried out, with blood pressure serving as the mediator and moderator, ACAG as the independent variable, and eGFR and ACR as the dependent variables. Finally, the study developed ACAG-based models for predicting kidney function decline. Higher ACAG is identified as an independent risk factor for eGFR &lt; 60 mL/minute/1.73 m<sup>2</sup> and ACR ≥ 30 mg/g. Results from RCS indicate a non-linear relationship between ACAG and eGFR, as well as between ACAG and ACR. The mediation effect analysis revealed that DBP mediated the relationship between ACAG and eGFR. Analysis on moderation effect demonstrated that SBP played a significant role in moderating the interaction between ACAG and ACR. Moreover, the models based on ACAG showed strong performance. The levels of ACAG are found to be independently associated with both eGFR and ACR. Additionally, ACAG shows promise as a new and dependable biomarker for predicting the decline in kidney function in hypertensive patients.
DOI: 10.6084/m9.figshare.26463203
title: Causal relationship between 731 immune cells and the risk of diabetic nephropathy: a two‑sample bidirectional Mendelian randomization study

description: Previous observational studies have indicated associations between various immune cells and diabetic nephropathy (DN). However, the causality remains unclear. We aimed to further evaluate the causal association between immune cells and DN using bidirectional two-sample Mendelian randomization (MR) analysis. The DN data were retrieved from the IEU OpenGWAS Project database, while the data for 731 immune cells were sourced from GWAS summary statistics by Orru ̀ et al. The investigation into the causal relationship between immune cells and DN employed the inverse variance weighted (IVW), weighted median (WME), and MR-Egger methods. The stability and reliability of the findings underwent evaluation through Cochran’s Q test, MR-Egger intercept’s <i>P</i>-value, MR-PRESSO, and Leave-One-Out (LOO) method. The IVW estimates suggested a positive causal effect of CD25 on IgD-CD38dim B cell, CD25 on naive-mature B cell, CD127 on granulocyte, SSC-A on HLA DR + Natural Killer, HLA DR on plasmacytoid Dendritic Cell, and HLA DR on Dendritic Cell on DN. Conversely, the abundance of Myeloid Dendritic Cell, CD62L- Dendritic Cell �ndritic Cell, CD86+ myeloid Dendritic Cell �ndritic Cell, CD14- CD16-, CX3CR1 on CD14- CD16-, and SSC-A on CD4+ T cell had negative causal effects on DN. However, after correcting the <i>P</i> value for significant causality results using the FDR method, it was concluded that only Myeloid Dendritic Cells had a causal relationship with DN (FDR-<i>p</i> = 0.041), while the other immune cells showed no significant association with DN, so their relationship was suggestive. The results were stable with no observed horizontal pleiotropy and heterogeneity. Reverse MR analysis indicated no causal relationship between DN and the increased risk of positively identified immune cells. This study provides an initial insight into the genetic perspective of the causal relationship between immune cells and DN. It establishes a crucial theoretical foundation for future endeavors in precision medicine and individualized treatment.
DOI: 10.6084/m9.figshare.26232708
title: The importance of paraoxonase 1 activity in chronic kidney disease

description: Paraoxonase 1 (PON1) is one of the most significant antioxidative enzymes associated with high-density lipoprotein (HDL). It has been proved that is involved in the pathogenesis of many diseases including chronic kidney disease (CKD). The association between PON1 and CKD seems to be mutual, such that the disease produces a significant decrease in PON1 activity levels, while the genetics of PON1 may affect the risk of susceptibility to CKD. Recent studies reveal that the decrease in serum PON1 activity observed in non-dialyzed and dialyzed CKD patients as well as in renal transplant (RT) patients is linked to an increased vulnerability to atherosclerosis. We intend to summarize current literature concerning PON1 activity in CKD, highlighting on the main determinants of PON1 activity, its association with oxidative stress, the impact of its genetic polymorphism on the disease development, the effect of drugs and nutritional state. Furthermore, evidence supporting the implication of reduced PON1 activity in the incident of cardiovascular disease in CKD patients, is also examined. It appears that despite the lack of standardization of PON1 activity measurement, PON1 remains a valuable biomarker for the researchers through the last decades, which contributes to the assessment of the antioxidant status having prognostic benefit on adverse clinical outcomes at various stages and etiologies of kidney disease.
DOI: 10.6084/m9.figshare.26232708.v1
title: The importance of paraoxonase 1 activity in chronic kidney disease

description: Paraoxonase 1 (PON1) is one of the most significant antioxidative enzymes associated with high-density lipoprotein (HDL). It has been proved that is involved in the pathogenesis of many diseases including chronic kidney disease (CKD). The association between PON1 and CKD seems to be mutual, such that the disease produces a significant decrease in PON1 activity levels, while the genetics of PON1 may affect the risk of susceptibility to CKD. Recent studies reveal that the decrease in serum PON1 activity observed in non-dialyzed and dialyzed CKD patients as well as in renal transplant (RT) patients is linked to an increased vulnerability to atherosclerosis. We intend to summarize current literature concerning PON1 activity in CKD, highlighting on the main determinants of PON1 activity, its association with oxidative stress, the impact of its genetic polymorphism on the disease development, the effect of drugs and nutritional state. Furthermore, evidence supporting the implication of reduced PON1 activity in the incident of cardiovascular disease in CKD patients, is also examined. It appears that despite the lack of standardization of PON1 activity measurement, PON1 remains a valuable biomarker for the researchers through the last decades, which contributes to the assessment of the antioxidant status having prognostic benefit on adverse clinical outcomes at various stages and etiologies of kidney disease.
DOI: 10.6084/m9.figshare.26463203.v1
title: Causal relationship between 731 immune cells and the risk of diabetic nephropathy: a two‑sample bidirectional Mendelian randomization study

description: Previous observational studies have indicated associations between various immune cells and diabetic nephropathy (DN). However, the causality remains unclear. We aimed to further evaluate the causal association between immune cells and DN using bidirectional two-sample Mendelian randomization (MR) analysis. The DN data were retrieved from the IEU OpenGWAS Project database, while the data for 731 immune cells were sourced from GWAS summary statistics by Orru ̀ et al. The investigation into the causal relationship between immune cells and DN employed the inverse variance weighted (IVW), weighted median (WME), and MR-Egger methods. The stability and reliability of the findings underwent evaluation through Cochran’s Q test, MR-Egger intercept’s <i>P</i>-value, MR-PRESSO, and Leave-One-Out (LOO) method. The IVW estimates suggested a positive causal effect of CD25 on IgD-CD38dim B cell, CD25 on naive-mature B cell, CD127 on granulocyte, SSC-A on HLA DR + Natural Killer, HLA DR on plasmacytoid Dendritic Cell, and HLA DR on Dendritic Cell on DN. Conversely, the abundance of Myeloid Dendritic Cell, CD62L- Dendritic Cell �ndritic Cell, CD86+ myeloid Dendritic Cell �ndritic Cell, CD14- CD16-, CX3CR1 on CD14- CD16-, and SSC-A on CD4+ T cell had negative causal effects on DN. However, after correcting the <i>P</i> value for significant causality results using the FDR method, it was concluded that only Myeloid Dendritic Cells had a causal relationship with DN (FDR-<i>p</i> = 0.041), while the other immune cells showed no significant association with DN, so their relationship was suggestive. The results were stable with no observed horizontal pleiotropy and heterogeneity. Reverse MR analysis indicated no causal relationship between DN and the increased risk of positively identified immune cells. This study provides an initial insight into the genetic perspective of the causal relationship between immune cells and DN. It establishes a crucial theoretical foundation for future endeavors in precision medicine and individualized treatment.
DOI: 10.6084/m9.figshare.28296208
title: Mendelian randomization analysis revealed that albuminuria is the key factor affecting socioeconomic status in CKD patients

description: Previous studies indicate a strong correlation between the incidence of chronic kidney disease (CKD) and lower economic status. However, these studies often struggle to delineate a clear cause–effect relationship, leaving healthcare providers uncertain about how to manage kidney disease in a way that improves patients’ financial outcomes. Our study aimed to explore and establish a causal relationship between CKD and socioeconomic status, identifying critical influencing factors. We utilized summary meta-analysis data from the CKDGen Consortium and UK Biobank. Genetic variants identified from these sources served as instrumental variables (IVs) to estimate the association between CKD and socioeconomic status. The presence or absence of CKD, estimated glomerular filtration rate (eGFR), and albuminuria were used as exposures, while income and regional deprivation were analyzed as outcomes. We employed the R packages ‘TwoSampleMR’ and ‘Mendelianrandomization’ to conduct both univariable and multivariable Mendelian randomization (MR) analyses, assessing for potential pleiotropy and heterogeneity. Our univariable MR analysis revealed a significant causal relationship between high levels of albuminuria and lower income (OR = 0.84, 95% CI: 0.73–0.96, <i>p</i> = 0.013), with no significant pleiotropy detected. In the multivariable MR analysis, both CKD (OR = 0.867, 95% CI: 0.786–0.957, <i>p</i> = 0.0045) and eGFR (OR = 0.065, 95% CI: 0.010–0.437, <i>p</i> = 0.0049) exhibited significant effects on income. This study underscores that higher albuminuria levels in CKD patients are associated with decreased income and emphasizes the importance of effective management and treatment of albuminuria in CKD patients to mitigate both social and personal economic burdens.
DOI: 10.6084/m9.figshare.28296208.v1
title: Mendelian randomization analysis revealed that albuminuria is the key factor affecting socioeconomic status in CKD patients

description: Previous studies indicate a strong correlation between the incidence of chronic kidney disease (CKD) and lower economic status. However, these studies often struggle to delineate a clear cause–effect relationship, leaving healthcare providers uncertain about how to manage kidney disease in a way that improves patients’ financial outcomes. Our study aimed to explore and establish a causal relationship between CKD and socioeconomic status, identifying critical influencing factors. We utilized summary meta-analysis data from the CKDGen Consortium and UK Biobank. Genetic variants identified from these sources served as instrumental variables (IVs) to estimate the association between CKD and socioeconomic status. The presence or absence of CKD, estimated glomerular filtration rate (eGFR), and albuminuria were used as exposures, while income and regional deprivation were analyzed as outcomes. We employed the R packages ‘TwoSampleMR’ and ‘Mendelianrandomization’ to conduct both univariable and multivariable Mendelian randomization (MR) analyses, assessing for potential pleiotropy and heterogeneity. Our univariable MR analysis revealed a significant causal relationship between high levels of albuminuria and lower income (OR = 0.84, 95% CI: 0.73–0.96, <i>p</i> = 0.013), with no significant pleiotropy detected. In the multivariable MR analysis, both CKD (OR = 0.867, 95% CI: 0.786–0.957, <i>p</i> = 0.0045) and eGFR (OR = 0.065, 95% CI: 0.010–0.437, <i>p</i> = 0.0049) exhibited significant effects on income. This study underscores that higher albuminuria levels in CKD patients are associated with decreased income and emphasizes the importance of effective management and treatment of albuminuria in CKD patients to mitigate both social and personal economic burdens.
DOI: 10.6084/m9.figshare.27965171
title: Risk factors for mortality in patients with sepsis on extracorporeal membrane oxygenation and/or continuous renal replacement therapy: a retrospective cohort study based on MIMIC-IV database

description: This study aimed to identify risk factors for mortality in septic patients undergoing extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapy (CRRT). Data from the MIMIC-IV database were retrospectively reviewed for 24,502 septic patients treated with ECMO or CRRT between 2008 and 2019. After applying inclusion and exclusion criteria, 70 patients receiving ECMO, 513 receiving CRRT, and 22 receiving both were included in the final analysis. Univariate and multivariate stepwise Cox regression analyses were performed to identify independent risk factors for mortality. Model performance was assessed using receiver operating characteristic (ROC) curve analysis. We also provided model-agnostic explanations for each Cox regression model. For septic patients on ECMO, prothrombin time (per 1-s increase, HR 1.037, 95% CI 1.007–1.068, <i>p</i> = .015) was the key independent risk factor. For septic patients undergoing CRRT, SOFA score (per one-point increase, HR 1.100, 95% CI 1.055–1.147, <i>p</i> &lt; .001) was the most significant factor. For septic patients requiring both ECMO and CRRT, prior history of hypertension (HR 4.342, 95% CI 1.332–14.153, <i>p</i> = .015) was the sole independent risk factor. ROC analysis showed satisfactory model performance (AUC &gt; 0.75). For septic patients requiring ECMO, prothrombin time was the key independent risk factor. For those needing CRRT, SOFA score was the most significant independent risk factor. Prior history of hypertension was the primary independent risk factor for septic patients needing both CRRT and ECMO.