Renal Failure最新文献

Background: Adjusting dietary potassium intake based on 24-hour urinary potassium excretion is the primary method of preventing hyperkalemia. Currently, there is no accurate and convenient method for calculating maximum 24-hour urinary potassium excretion in kidney failure without replacement therapy patients. We developed and validated two new models to assess the upper limit of dietary potassium consumption in this high-risk cohort, using the maximum 24-hour urinary potassium excretion as a proxy.

Methods: The data of 145 kidney failure without replacement therapy patients with hyperkalemia was gathered. The prediction models were developed using multilayer perceptron and stepwise multiple linear regression utilizing a stochastic sample of 102 (70%) patients. Within the rest 43 (30%), the performance of various models was independently verified.

Results: The two new models had low bias (-0.02 and -0.57 mmol/24h vs 66.74 and 79.91 mmol/24h, mean absolute error = 5.57 and 5.22 vs 68.95 and 81.37), high accuracy (percentage of calculated values within_±30% of measured values = 83.45% and 84.14% vs 0.00% and 0.00%), high correlation with measured values (Spearman correlation coefficient = 0.72 and 0.72 vs 0.46 and 0.45, intraclass correlation coefficient = 0.67 and 0.70 vs 0.03 and 0.03) and high agreement with 24-hour urine potassium measurements (95% limits of agreement of Bland-Altman plot = 13.70 and 13.20 mmol/24h vs 113.8 and 191.3 mmol/24h).

Conclusion: These new models show high clinical application value for the calculation of maximum 24-hour urinary potassium excretion in kidney failure without replacement therapy patients with hyperkalemia.

Background: IgA nephropathy (IgAN) is a leading cause of chronic kidney disease, often associated with dyslipidemia and immune dysfunction. This study employs Mendelian randomization (MR) to investigate the causal relationship between plasma lipidomes and IgAN, with a focus on the potential mediating role of immune cells.

Methods: We analyzed the 179 genetically predicted plasma lipidomes and the IgAN gene using two-sample Mendelian randomization (TSMR) and multivariable MR based on summary-level data from a genome-wide association study, and the results were validated by liquid chromatography-mass spectrometry. Furthermore, we quantified the proportional effect of immune cell-mediated lipidomes on IgAN using TSMR.

Results: This study identified significant causal relationships of 3 lipidomes on IgAN risk by examining 179 lipidome traits as exposures. To investigate whether the impact of the 3 lipid groups on IgAN is specific, we performed TSMR analyses using 3 lipidomes as exposure factors and 4 nephritides as outcomes. Specifically, only phosphatidylinositol (18:1_20:4) was found to have a significant negative relationship with IgAN incidence (IVW method, p = 0.01, OR = 0.71, 95% CI = 0.55 - 0.92). Our further analysis focused on 8 immune cells associated with IgAN. We identified 2 immune cell phenotypes that may contribute to phosphatidylinositol (18:1_20:4)-mediated IgAN by careful screening.

Conclusions: Our findings provide robust genetic evidence supporting a causal link between plasma lipidomes and IgAN, with immune cells acting as potential mediators. Phosphatidylinositol (18:1_20:4) emerges as a promising biomarker for IgAN risk stratification, early detection, and therapeutic intervention. Modulating its plasma levels may offer novel avenues for IgAN management.

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.

Background: Chronic kidney disease (CKD) and impaired renal function have been implicated in venous thromboembolism (VTE), but their causal relationships remain uncertain. This study employs Mendelian randomization (MR) to elucidate the potential bidirectional causal effects between CKD, renal function biomarkers, and VTE.

Methods: We collated datasets from genome-wide association studies conducted among European individuals to perform MR analyses. The primary method utilized was the random-effect inverse variance-weighted (IVW) approach, with MR-Egger and the weighted median approaches employed as supplemental techniques. Several sensitivity studies were performed to assess the findings' robustness.

Results: We identified a link between elevated serum creatinine levels and both VTE (OR: 1.14, 95% CI: 1.05-1.24, p = 0.001) and PE (OR: 1.20, 95% CI: 1.08-1.33, p = 0.001). After outlier removal and Bonferroni correction, the Cr-VTE association lost significance (p = 0.005). A suggestive causal relationship was found between eGFR and VTE (OR: 0.38, 95% CI: 0.20-0.73, p = 0.004), DVT (OR: 0.37, 95% CI: 0.16-0.87, p = 0.022), and PE (OR: 0.29, 95% CI: 0.12-0.66, p = 0.004). No causal effects of CKD or BUN on VTE or its subtypes were observed. Reverse causality inferences did not reveal any meaningful results.

Conclusions: This MR analysis provides evidence that elevated serum creatinine is associated with a higher risk of VTE and PE, while reduced eGFR may be a potential risk factor for VTE and its subtypes. These findings highlight the need for proactive monitoring and preventive strategies in individuals with impaired renal function. Further studies are warranted to confirm these associations and explore underlying mechanisms.

Hemodialysis reactions (HDRs) are a type of hypersensitivity reactions (HSRs), such as complement activation-related pseudoallergy (CARPA) observed during nanoparticle infusions. Our study aimed to elucidate the mechanisms of human HDRs by focusing on hemodynamic and clinical chemistry changes of HSR-related or biocompatibility issues during human hemodialysis (HD) and the reinfusion of blood. Based on our recent animal experiments, we hypothesize that increased pulmonary arterial pressure (PAP), and increases in thromboxane B2 (TXB2) and complement 3a (C3a) plasma concentrations will likely manifest in, or at least predict, human HDRs during HD and blood reinfusion. To verify our hypothesis, we measured these parameters during high-flux HD in patients. Since direct PAP measurement was not possible, the plasma concentration of the N-terminal fragment of the brain natriuretic peptide (NT-proBNP) was determined for the noninvasive estimation of PAP. Our results show an increase in NT-proBNP and TXB2 during the reinfusion of extracorporeal blood. The plasma concentration of C3a increased in early HD already and remained elevated up to blood reinfusion. In conclusion, the observed changes in HSR-related parameters or biocompatibility issues in otherwise asymptomatic patients may suggest that a greater activation of these mechanisms could explain the development of human hemodialysis reactions.

Immunoglobulin A nephropathy (IgAN) stands as the most prevalent primary glomerulonephritis globally, almost half of patients progress to end-stage kidney disease (ESKD). However, the precise pathogenesis of IgAN remains elusive. Long non-coding RNAs (lncRNAs), non-protein-coding transcripts that regulate gene expression, have been found to exhibit distinct expression patterns in various disease states. Comprehensive bioinformatic analyses from IgAN patients have uncovered differential expression of lncRNAs such as HOTAIR, H19, and MALAT1. Furthermore, a single nucleotide polymorphism in MIR31HG has been linked to IgAN susceptibility and correlated with clinical markers like urinary red blood cells and hemoglobin levels. Lnc-TSI and lnc-CHAF1B-3, specifically expressed in the kidneys of IgAN patients, exhibit associations with renal fibrosis indices and the degree of kidney function deterioration, influencing the progression of renal fibrosis through distinct signaling pathways. Additionally, renal intercellular adhesion molecule 1 (ICAM-1) related long noncoding RNA (ICR) levels positively correlate with IgAN severity and contribute to renal fibrosis, whereas serum H19 serves as an independent protective factor against IgAN. Notably, experiments have validated the involvement of PTTG3P, lnc-CHAF1B-3, and CRNDE in the pathogenesis of IgAN. Nevertheless, data on the roles of lncRNAs in IgAN pathogenesis and their potential as biomarkers remain limited, and effective therapeutic options for IgAN are similarly rare. Therefore, there is an urgent need to bridge this knowledge gap. This article presents a review of current literature on lncRNAs related to IgAN, aiming to consolidate existing findings and identify future research avenues.

Background: Maintenance hemodialysis (MHD) patients frequently exhibit immune dysregulation and gut dysbiosis, both of which contribute to increased infection risk and adverse outcomes. However, the relationship between gut microbial composition and immune competence in this population remains underexplored.

Methods: This study assessed 45 MHD patients and 30 healthy controls, stratifying MHD patients into immunocompetent (HD-NLI, CD4⁺/CD8⁺ ≥ 1) and immunodeficient (HD-LI, CD4⁺/CD8⁺ < 1) groups. Circulating cytokines (IL-6, IL-10, IL-12, TNF-α, IFN-γ) were quantified using ELISA. Gut microbiota profiles were derived via 16S rRNA gene sequencing (V3-V4 regions), followed by QIIME2 and LEfSe-based bioinformatics analyses.

Results: HD-LI patients displayed severe T cell dysregulation and elevated pro-inflammatory cytokines. Compared to controls, HD patients had reduced abundance of beneficial taxa (e.g., Prevotella copri, Bacteroides vulgatus, Agathobacter), and enrichment of pro-inflammatory taxa (e.g., Escherichia-Shigella, Blautia, Citrobacter). LEfSe identified 39 discriminatory taxa with distinct immune group signatures. Redundancy analysis revealed that CD4⁺ levels, CD4⁺/CD8⁺ ratios, and TNF-α significantly shaped microbiota composition. Correlation analysis confirmed strong associations between immune parameters and microbial taxa involved in short-chain fatty acid (SCFA) metabolism.

Conclusion: This study provides novel evidence linking gut microbial dysbiosis to immune impairment in MHD patients. The findings suggest that SCFA-producing bacteria are depleted in immunodeficient states, offering a potential target for microbiota-directed immunomodulatory therapies in ESRD.