cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.29039750.v1
title: Inflammatory markers mediate association of AIP with kidney failure risk: data from National Health and Nutrition Examination Survey (NHANES) 2005–2018

description: Dyslipidemia and inflammation often coexist in the progression of kidney failure, with the atherosclerosis index of plasma (AIP) serving as a valuable marker for monitoring dyslipidemia. This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2018, involving a total of 10,358 participants. AIP was calculated as the logarithmic ratio (base 10) of triglycerides to high-density lipoprotein cholesterol (log10[TG/HDL-C]), while kidney failure was assessed through self-reported physician diagnosis. Logistic regression models and restricted cubic splines (RCS) were utilized to examine the association between AIP and the risk of kidney failure, with additional subgroup analyses performed to explore potential interactions. Mediation analyses were conducted to investigate whether inflammatory markers mediated the relationship between AIP and kidney failure. In logistic regression, after adjusting for all covariates, AIP was found to be positively associated with the risk of kidney failure [OR = 1.74 (95% CI: 1.04–2.92)], and a linear relationship between AIP and kidney failure risk was observed (P-non-linear = 0.4050). Mediation analysis revealed that segmented neutrophils, eosinophils, and monocytes partially mediated the association between AIP and kidney failure, with mediation proportions of 19.65%, 2.44%, and 7.25%, respectively. These findings suggest that Higher AIP was associated with an increased risk of kidney failure, with segmented neutrophils, eosinophils, and monocytes serving as partial mediators. The results provide valuable insights into the role of inflammation in kidney failure and highlight potential avenues for its prevention.
DOI: 10.6084/m9.figshare.28522570
title: The association between immune cells and acute kidney injury: insights from Mendelian randomization

description: Immune disorder is a prominent feature of acute kidney injury (AKI). However, the specific role of different immune cell phenotypes in the pathogenesis of AKI remains poorly understood. The aim of this study was to investigate the relevance of 731 immune phenotypes to AKI. We obtained data on 731 immune cell phenotypes from the GWAS Catalog and Open GWAS databases and undertook a series of quality control measures to identify exposure-related instrumental variables (IV). Data on acute renal failure (ARF) and rapid kidney function decline were obtained from the Finngen R11 and CKDGen databases as an outcome. Subsequently, we performed two-sample Mendelian randomization (MR) using inverse variance weights to explore the causal relationship between 731 immune cell characteristics and ARF and rapid kidney function declineas at the gene level. Sensitivity analyses, including leave-one-out and other MR analysis models, were performed. At the significance level corrected by Bonferroni, 9 immune phenotypes, including CD25 on IgD + CD24- B cell, were associated with ARF; 4 immune phenotypes, including SSC-A on plasmacytoid dendritic cell, were associated with rapid kidney function decline. Sensitivity analysis indicated robust results. Our study demonstrates a strong causal relationship between specific types of immune cells and AKI by genetic means, providing valuable insights for future clinical studies.
DOI: 10.6084/m9.figshare.28522570.v1
title: The association between immune cells and acute kidney injury: insights from Mendelian randomization

description: Immune disorder is a prominent feature of acute kidney injury (AKI). However, the specific role of different immune cell phenotypes in the pathogenesis of AKI remains poorly understood. The aim of this study was to investigate the relevance of 731 immune phenotypes to AKI. We obtained data on 731 immune cell phenotypes from the GWAS Catalog and Open GWAS databases and undertook a series of quality control measures to identify exposure-related instrumental variables (IV). Data on acute renal failure (ARF) and rapid kidney function decline were obtained from the Finngen R11 and CKDGen databases as an outcome. Subsequently, we performed two-sample Mendelian randomization (MR) using inverse variance weights to explore the causal relationship between 731 immune cell characteristics and ARF and rapid kidney function declineas at the gene level. Sensitivity analyses, including leave-one-out and other MR analysis models, were performed. At the significance level corrected by Bonferroni, 9 immune phenotypes, including CD25 on IgD + CD24- B cell, were associated with ARF; 4 immune phenotypes, including SSC-A on plasmacytoid dendritic cell, were associated with rapid kidney function decline. Sensitivity analysis indicated robust results. Our study demonstrates a strong causal relationship between specific types of immune cells and AKI by genetic means, providing valuable insights for future clinical studies.
DOI: 10.6084/m9.figshare.28929905
title: Uremic toxins removal and iron status: a medium-term comparison between 4 dialysis techniques (EMPIRE study)

description: Recent evidence documented that dialyzers and hemodialytic techniques yield different dialytic performances. The study aims to compare uremic toxins removal and iron status between on-line hemodiafiltration (OL-HDF), high-flux hemodialysis (HF-HD), expanded hemodialysis (HDx), and HFR Aequilibrium (HFR-Aeq). A single-center retrospective observational study enrolled 52 patients on chronic HD. Each study group (HFR-Aeq, HDx, HF-HD, and OL-HDF) included 13 patients. Naïve patients for each of the treatments were considered. Serum samples were collected at baseline and after 12–24–48 weeks from the enrollment. Intragroup comparison was performed using Friedman’s test whereas longitudinal data were compared using linear mixed models (LMMs). HDx showed a progressive improvement in the removal of urea (<i>p</i> = 0.043), λ -free light chains (<i>p</i> = 0.033), and transferrin saturation (<i>p</i> = 0.011) compared to other techniques. A nearly significant slope of β2 M was observed (<i>p</i> = 0.066). Also HFR-Aeq showed a near significant reduction in λ FLC values (<i>p</i> = 0.05) and a nearly significant increase in albumin levels (<i>p</i> = 0.07). HFR-Aeq provides uremic toxins removal comparable to other traditional techniques (HF-HD, OL-HDF). HDx confirmed its superiority in the removal of uremic toxins as urea and λ FLC and surprisingly enhanced TSAT by a possible anti-inflammatory effect not ascertained in the present study. The utilization of non-optimal convective volumes likely vanishes the promising findings of OL-HDF.
DOI: 10.6084/m9.figshare.28929905.v1
title: Uremic toxins removal and iron status: a medium-term comparison between 4 dialysis techniques (EMPIRE study)

description: Recent evidence documented that dialyzers and hemodialytic techniques yield different dialytic performances. The study aims to compare uremic toxins removal and iron status between on-line hemodiafiltration (OL-HDF), high-flux hemodialysis (HF-HD), expanded hemodialysis (HDx), and HFR Aequilibrium (HFR-Aeq). A single-center retrospective observational study enrolled 52 patients on chronic HD. Each study group (HFR-Aeq, HDx, HF-HD, and OL-HDF) included 13 patients. Naïve patients for each of the treatments were considered. Serum samples were collected at baseline and after 12–24–48 weeks from the enrollment. Intragroup comparison was performed using Friedman’s test whereas longitudinal data were compared using linear mixed models (LMMs). HDx showed a progressive improvement in the removal of urea (<i>p</i> = 0.043), λ -free light chains (<i>p</i> = 0.033), and transferrin saturation (<i>p</i> = 0.011) compared to other techniques. A nearly significant slope of β2 M was observed (<i>p</i> = 0.066). Also HFR-Aeq showed a near significant reduction in λ FLC values (<i>p</i> = 0.05) and a nearly significant increase in albumin levels (<i>p</i> = 0.07). HFR-Aeq provides uremic toxins removal comparable to other traditional techniques (HF-HD, OL-HDF). HDx confirmed its superiority in the removal of uremic toxins as urea and λ FLC and surprisingly enhanced TSAT by a possible anti-inflammatory effect not ascertained in the present study. The utilization of non-optimal convective volumes likely vanishes the promising findings of OL-HDF.
DOI: 10.6084/m9.figshare.28902016
title: Causal associations between circulating metabolites and chronic kidney disease: a Mendelian randomization study

description: Circulating metabolites have been associated with cross-sectional renal function in population-based research. Nevertheless, there is currently little proof to support the idea that metabolites either cause or prevent renal function. New treatment targets and ways to screen individuals with impaired renal function will be made possible <i>via</i> an in-depth analysis of the causal relationship between blood metabolites and renal function. We assessed the causal relationship between 452 serum metabolites and six renal phenotypes (CKD, rapid progression to CKD [CKDi25], rapid eGFR decline [CKD rapid3], dialysis, estimated glomerular filtration rate, and blood urea nitrogen) using univariate Mendelian randomization, primarily employing the inverse variance weighted method with robust sensitivity analyses. Heterogeneity and pleiotropy were examined <i>via</i> Cochrane’s Q test and MR-Egger regression, and statistical significance was adjusted using Bonferroni correction. To assess potential adverse effects of metabolite modulation, we conducted a phenome-wide Mendelian randomization analysis, followed by multivariate Mendelian randomization to adjust for confounders. We identified glycine and N-acetylornithine as potential causal mediators of CKD and renal dysfunction. Notably, lowering glycine levels may increase the risk of cholelithiasis and cholecystitis, while reducing N-acetylornithine could have unintended effects on tinnitus. Glycine and N-acetylornithine represent promising therapeutic targets for CKD and renal function preservation, but their modulation requires careful risk-benefit assessment to avoid adverse effects.
DOI: 10.6084/m9.figshare.28902016.v1
title: Causal associations between circulating metabolites and chronic kidney disease: a Mendelian randomization study

description: Circulating metabolites have been associated with cross-sectional renal function in population-based research. Nevertheless, there is currently little proof to support the idea that metabolites either cause or prevent renal function. New treatment targets and ways to screen individuals with impaired renal function will be made possible <i>via</i> an in-depth analysis of the causal relationship between blood metabolites and renal function. We assessed the causal relationship between 452 serum metabolites and six renal phenotypes (CKD, rapid progression to CKD [CKDi25], rapid eGFR decline [CKD rapid3], dialysis, estimated glomerular filtration rate, and blood urea nitrogen) using univariate Mendelian randomization, primarily employing the inverse variance weighted method with robust sensitivity analyses. Heterogeneity and pleiotropy were examined <i>via</i> Cochrane’s Q test and MR-Egger regression, and statistical significance was adjusted using Bonferroni correction. To assess potential adverse effects of metabolite modulation, we conducted a phenome-wide Mendelian randomization analysis, followed by multivariate Mendelian randomization to adjust for confounders. We identified glycine and N-acetylornithine as potential causal mediators of CKD and renal dysfunction. Notably, lowering glycine levels may increase the risk of cholelithiasis and cholecystitis, while reducing N-acetylornithine could have unintended effects on tinnitus. Glycine and N-acetylornithine represent promising therapeutic targets for CKD and renal function preservation, but their modulation requires careful risk-benefit assessment to avoid adverse effects.
DOI: 10.6084/m9.figshare.29039756
title: HIF-PHIs associated with embolic and thrombotic events: a real-world pharmacovigilance study based on the Japan Adverse Drug Event Report database

description: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) play an important role in the treatment of renal anemia. However, some studies suggest a potential link between HIF-PHIs and increased thrombosis risk, though these findings are inconsistent and lack large-scale clinical support. We aim to summarize embolic and thrombotic events associated with HIF-PHIs in different populations in real world, especially among high-risk patients. Using the Japan Adverse Drug Event Report (JADER) database from January 1, 2020, to September 30, 2023, a disproportionality analysis was employed to identify embolic and thrombotic events associated with HIF-PHIs using the reporting odds ratios (ROR) and information component (IC). We also evaluated the time to onset among different populations. From January 2020 to September 2023, the JADER database reported a total of 253,599 cases, including 1,222 cases of embolic and thrombotic events, which represented 30.44% of all HIF-PHIs reported. Embolic and thrombotic events (ROR = 6.68) related to HIF-PHIs is positive signal, with the strongest signal observed for vessel type unspecified and mixed arterial and venous (ROR = 7.97). The signal intensity is higher in females than in males (<i>p</i> = 0.008) and also greater in the non-dialysis population compared to the dialysis population (<i>p</i> &lt; 0.001). The median onset time was shorter in the dialysis population than in the non-dialysis population (days: 27 vs. 47, <i>p</i> = 0.016). Attention to embolic and thrombotic events associated with HIF-PHIs is essential, with careful selection of specific types based on underlying diseases, sex, age, and indications.
DOI: 10.6084/m9.figshare.29039756.v1
title: HIF-PHIs associated with embolic and thrombotic events: a real-world pharmacovigilance study based on the Japan Adverse Drug Event Report database

description: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) play an important role in the treatment of renal anemia. However, some studies suggest a potential link between HIF-PHIs and increased thrombosis risk, though these findings are inconsistent and lack large-scale clinical support. We aim to summarize embolic and thrombotic events associated with HIF-PHIs in different populations in real world, especially among high-risk patients. Using the Japan Adverse Drug Event Report (JADER) database from January 1, 2020, to September 30, 2023, a disproportionality analysis was employed to identify embolic and thrombotic events associated with HIF-PHIs using the reporting odds ratios (ROR) and information component (IC). We also evaluated the time to onset among different populations. From January 2020 to September 2023, the JADER database reported a total of 253,599 cases, including 1,222 cases of embolic and thrombotic events, which represented 30.44% of all HIF-PHIs reported. Embolic and thrombotic events (ROR = 6.68) related to HIF-PHIs is positive signal, with the strongest signal observed for vessel type unspecified and mixed arterial and venous (ROR = 7.97). The signal intensity is higher in females than in males (<i>p</i> = 0.008) and also greater in the non-dialysis population compared to the dialysis population (<i>p</i> &lt; 0.001). The median onset time was shorter in the dialysis population than in the non-dialysis population (days: 27 vs. 47, <i>p</i> = 0.016). Attention to embolic and thrombotic events associated with HIF-PHIs is essential, with careful selection of specific types based on underlying diseases, sex, age, and indications.
DOI: 10.6084/m9.figshare.28193467
title: Moderate-severe aortic arch calcification and high serum alkaline phosphatase co-modify the risk of cardiovascular events and mortality among chronic hemodialysis patients

description: Patients with end-stage kidney disease undergoing chronic hemodialysis (HD) have an unparalleled risk of vascular calcification (VC) and high alkaline phosphatase (Alk-P) levels. However, whether VC contributed to the cardiovascular risk modified by serum Alk-P levels was not addressed in the population. A retrospective cohort study was conducted on chronic HD patients, between October 1 and December 31, 2018, with aortic arch calcification (AoAC) scores and serum Alk-P levels. Patients were categorized into four groups: non-to-mild AoAC/low Alk-P, non-to-mild AoAC/high Alk-P, moderate-to-severe AoAC/low Alk-P, and moderate-to-severe AoAC/high Alk-P. The Cox proportional hazard model and Kaplan–Meier analysis were used to evaluate the risks of major adverse cardiovascular effects (MACEs) and cardiovascular and all-cause mortality after multivariate adjustment. Among 376 chronic HD patients recruited, 125 (33%) had non-to-mild AoAC/low Alk-P, 76 (20%) had non-to-mild AoAC/high Alk-P, 89 (24%) had moderate-to-severe AoAC/low Alk-P, and 86 (23%) had moderate-to-severe AoAC/high Alk-P. After 3 years of follow-up, patients with coexisting moderate-to-severe AoAC and high Alk-P had a higher risk of MACEs (aHR 1.76; 95% CI 1.06–2.92), and cardiovascular (aHR 2.49; 95% CI 1.21–5.11) and all-cause mortality (aHR 2.67; 95% CI 1.39–5.13) compared to those with non-to-mild AoAC/low Alk-P even after adjustments for significant clinical variables. In chronic HD patients, moderate to severe AoAC co-existed with high Alk-P levels and enhanced the risk of MACEs and cardiovascular and all-cause mortality. Interventions to attenuate these risk factors simultaneously should be emphasized in this population.
DOI: 10.6084/m9.figshare.28193467.v1
title: Moderate-severe aortic arch calcification and high serum alkaline phosphatase co-modify the risk of cardiovascular events and mortality among chronic hemodialysis patients

description: Patients with end-stage kidney disease undergoing chronic hemodialysis (HD) have an unparalleled risk of vascular calcification (VC) and high alkaline phosphatase (Alk-P) levels. However, whether VC contributed to the cardiovascular risk modified by serum Alk-P levels was not addressed in the population. A retrospective cohort study was conducted on chronic HD patients, between October 1 and December 31, 2018, with aortic arch calcification (AoAC) scores and serum Alk-P levels. Patients were categorized into four groups: non-to-mild AoAC/low Alk-P, non-to-mild AoAC/high Alk-P, moderate-to-severe AoAC/low Alk-P, and moderate-to-severe AoAC/high Alk-P. The Cox proportional hazard model and Kaplan–Meier analysis were used to evaluate the risks of major adverse cardiovascular effects (MACEs) and cardiovascular and all-cause mortality after multivariate adjustment. Among 376 chronic HD patients recruited, 125 (33%) had non-to-mild AoAC/low Alk-P, 76 (20%) had non-to-mild AoAC/high Alk-P, 89 (24%) had moderate-to-severe AoAC/low Alk-P, and 86 (23%) had moderate-to-severe AoAC/high Alk-P. After 3 years of follow-up, patients with coexisting moderate-to-severe AoAC and high Alk-P had a higher risk of MACEs (aHR 1.76; 95% CI 1.06–2.92), and cardiovascular (aHR 2.49; 95% CI 1.21–5.11) and all-cause mortality (aHR 2.67; 95% CI 1.39–5.13) compared to those with non-to-mild AoAC/low Alk-P even after adjustments for significant clinical variables. In chronic HD patients, moderate to severe AoAC co-existed with high Alk-P levels and enhanced the risk of MACEs and cardiovascular and all-cause mortality. Interventions to attenuate these risk factors simultaneously should be emphasized in this population.
DOI: 10.6084/m9.figshare.28467511
title: The association between the cystatin C- and creatinine-based estimated GFR ratio and post-ablation outcomes in patients with atrial fibrillation

description: The difference between the cystatin C-based eGFR (eGFRcys) and the creatinine-based eGFR (eGFRcr) is associated with the risk of developing atrial fibrillation (AF) risk. However, its impact on AF ablation outcomes is unknown. The associations between the baseline eGFR ratio (eGFRcys/eGFRcr) and the risk of experiencing post-ablation endpoints were evaluated on a continuous scale (restricted cubic splines) and by a priori defined centile categories with Cox proportional hazards regression models. The primary endpoints were AF recurrence and adverse events; the secondary endpoint was rehospitalization. Among 989 participants (49.2% women; mean age 65.7 years), 313 experienced AF recurrence after a median follow-up of 28 months. After full adjustment for confounding factors, a U-shaped association was observed between eGFR ratio and AF recurrence risk (minimum risk at 0.797). Although a U-shaped trend was observed, there was no statistically significant association between the eGFR ratio and adverse events or rehospitalization. Hazard ratios for AF recurrence, compared to the second quartile, were 1.68 (1.20–2.37) for the first quartile, 1.64 (1.15–2.34) for the third quartile, and 1.96 (1.37–2.80) for the fourth quartile. According to the subgroup analysis, the above association was strongly U-shaped for males and linear for females. In the AF population, both low and high eGFR ratios were associated with an increased risk of post-ablation AF recurrence.
DOI: 10.6084/m9.figshare.28467511.v1
title: The association between the cystatin C- and creatinine-based estimated GFR ratio and post-ablation outcomes in patients with atrial fibrillation

description: The difference between the cystatin C-based eGFR (eGFRcys) and the creatinine-based eGFR (eGFRcr) is associated with the risk of developing atrial fibrillation (AF) risk. However, its impact on AF ablation outcomes is unknown. The associations between the baseline eGFR ratio (eGFRcys/eGFRcr) and the risk of experiencing post-ablation endpoints were evaluated on a continuous scale (restricted cubic splines) and by a priori defined centile categories with Cox proportional hazards regression models. The primary endpoints were AF recurrence and adverse events; the secondary endpoint was rehospitalization. Among 989 participants (49.2% women; mean age 65.7 years), 313 experienced AF recurrence after a median follow-up of 28 months. After full adjustment for confounding factors, a U-shaped association was observed between eGFR ratio and AF recurrence risk (minimum risk at 0.797). Although a U-shaped trend was observed, there was no statistically significant association between the eGFR ratio and adverse events or rehospitalization. Hazard ratios for AF recurrence, compared to the second quartile, were 1.68 (1.20–2.37) for the first quartile, 1.64 (1.15–2.34) for the third quartile, and 1.96 (1.37–2.80) for the fourth quartile. According to the subgroup analysis, the above association was strongly U-shaped for males and linear for females. In the AF population, both low and high eGFR ratios were associated with an increased risk of post-ablation AF recurrence.