Renal Failure最新文献

Objective: To explore the risk factors for uric acid-lowering therapy-resistant gout (UALT-RG) and its relationships with the estimated glomerular filtration rate (eGFR), body roundness index (BRI), and visceral adiposity index (VAI) via 2007-2018 National Health and Nutrition Examination Survey (NHANES) data.

Methods: We calculated the BRI using waist circumference and standing height; the VAI using triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and body mass index (BMI); and the eGFR from serum creatinine levels. We also collected gout data. We explored the relationships of the eGFR, BRI, and VAI with UALT-RG risk via univariable and multivariable weighted logistic regression, trend analysis, and restricted cubic splines.

Results: Among the 1,811 patients with gout, ∼9.08% had UALT-RG; these patients were more likely to have obesity, comorbid diabetes (36% [27-47%] vs. 25% [22-28%]) or impaired kidney function (eGFR < 60 mL/min/1.73 m², 34.5% [27-43%] vs. 22.5% [20-26%]); be former smokers; and take colchicine (10% [5.6-19%] vs. 4.3% [2.8-6.7%]). Logistic regression and trend analysis suggested that an elevated BRI and decreased eGFR were independent risk factors and potential screening indicators for UALT-RG. Restricted cubic spline analysis revealed a negative linear trend between the eGFR and UALT-RG risk (p-overall < 0.0001) and a significant positive correlation between the BRI and UALT-RG risk (p-overall < 0.0001).

Conclusion: An increased BRI and decreased eGFR may be independent risk factors and assessment indicators for UALT-RG in U.S. adults. It is necessary to monitor serum urate levels more closely and conduct early multidisciplinary comanagement when gout is comorbid with visceral obesity and chronic kidney disease stages 3-5.

Objective: The study aimed to compare ultrasound-guided brachial plexus block (BPB) with local anesthesia (LA) on efficacy, safety and 12-month patency rate for percutaneous transluminal angioplasty (PTA) treatment of dysfunctional arteriovenous fistula (AVF).

Methods: Consecutive patients with dysfunctional AVF who underwent PTA from January 2021 to December 2022 were included. Overlap weighting was performed to adjust for significant differences between the two groups. The primary efficacy outcomes included visual analogue scale (VAS) score and 12-month target-lesion primary patency rate. The secondary efficacy outcomes included target-lesion primary-assisted patency rate, secondary patency rate, access-circuit thrombosis rate, access-circuit reintervention rate, and number of reinterventions within 12 months. Univariate analysis and multivariate analysis by log-binomial regression were used to identify the independent factors associated with intraoperative pain.

Results: 218 patients were included in the study: 82 patients underwent PTA under BPB and 136 patients underwent PTA under LA. After overlap weighting, the baseline, lesion characteristics and intraoperative details had no significant difference between the two groups. Patients under BPB had significantly lower VAS scores than those under LA (2.4 ± 1.4 vs 5.1 ± 1.9, p < 0.001). The 12-month target-lesion primary patency rate was significantly higher in the BPB group than that in the LA group (58.3% vs 40.0%, p = 0.037). The 12-month target-lesion primary-assisted patency rate and access-circuit secondary patency rate were significantly higher in the BPB group than those in the LA group (p = 0.023 and p = 0.028). The access-circuit thrombosis rate was significantly lower in the BPB group (10.0%) than that in the LA group (28.3%) (p = 0.011). BPB was the only independent factor associated with mild pain (p < 0.001, OR: 0.037, 95%CI: 0.011-0.119).

Conclusions: BPB could decrease the intraoperative pain and improve the 12-month primary patency rates compared with LA for patients underwent PTA treatment of dysfunctional AVF.

Background: Diabetic kidney disease (DKD) is a common and serious complication of diabetic mellitus (DM). More sensitive methods for early DKD prediction are urgently needed. This study aimed to set up DKD risk prediction models based on machine learning algorithms (MLAs) in patients with type 2 DM (T2DM).

Methods: The electronic health records of 12,190 T2DM patients with 3-year follow-ups were extracted, and the dataset was divided into a training and testing dataset in a 4:1 ratio. The risk variables for DKD development were ranked and selected to establish forecasting models. The performance of models was further evaluated by the indexes of sensitivity, specificity, positive predictive value, negative predictive value, accuracy, as well as F1 score, using the testing dataset. The value of accuracy was used to select the optimal model.

Results: Using the importance ranking in the random forest package, the variables of age, urinary albumin-to-creatinine ratio, serum cystatin C, estimated glomerular filtration rate, and neutrophil percentage were selected as the predictors for DKD onset. Among the seven forecasting models constructed by MLAs, the accuracy of the Light Gradient Boosting Machine (LightGBM) model was the highest, indicated that the LightGBM algorithms might perform the best for predicting 3-year risk of DKD onset.

Conclusions: Our study could provide powerful tools for early DKD risk prediction, which might help optimize intervention strategies and improve the renal prognosis in T2DM patients.

Smoking is widely acknowledged for its harmful effects on multiple organs. However, its specific causal relationship with chronic kidney disease (CKD) remains uncertain. This study applied bivariate causal analysis and two-sample Mendelian randomization (MR) methods to examine the association between various smoking behaviors - initiation, cessation, age at initiation, cigarettes smoked per day, and lifetime smoking - and CKD, using genome-wide data. The inverse variance weighted (IVW) method was the primary analytical tool, supported by sensitivity analyses, pleiotropy assessments, and mediation analyses. External validation was conducted using independent datasets. The results revealed positive associations between CKD and smoking initiation (Pivw = 1.8 × 10^-2, OR = 1.192), earlier age at initiation (Pivw = 2.3 × 10^-3, OR = 1.481), cigarettes smoked per day (Pivw = 8.8 × 10^-3, OR = 1.216), and lifetime smoking (Pivw = 2.3 × 10^-7, OR = 2.445). In contrast, smoking cessation demonstrated a protective effect against CKD (Pivw = 4.0 × 10^-12, OR = 0.791). External validation results aligned with the primary findings, and the absence of significant heterogeneity confirmed the robustness of the MR analysis. Additionally, the effect of smoking on CKD was mediated by factors such as body mass index, cardiovascular disease, hypertension, and type 2 diabetes. These findings identify smoking as a contributing factor to CKD and suggest that reducing smoking prevalence could significantly lower the incidence of CKD in the population.

Background: Diabetic kidney disease (DKD), characterized by mesangial fibrosis and renal dysfunction, is a major microvascular complication of diabetes. Studies have shown that miRNAs are closely related to the progression of DKD. Therefore, in this study, we aimed to explore whether miR-1225-3p can regulate Smad ubiquitin regulatory factor 2 (SMURF2)-mediated carbohydrate response element binding protein (ChREBP) ubiquitination through Rho GTPase-activating protein 5 (ARHGAP5) to affect fibrosis in DKD.

Methods: DKD mice were established by intraperitoneally injecting streptozocin (STZ), and a DKD cell model was generated by culturing in media supplemented with 25 mmol/L glucose (high glucose, HG). StarBase was used to predict the target binding sites between miR-1225-3p and ARHGAP5, and a dual-luciferase reporter gene assay was used to verify this relationship. Western blotting, RT-qPCR, flow cytometry, immunoprecipitation, ELISAs, HE staining, and Masson staining were used to detect relevant indicators.

Results: ARHGAP5 and SMURF2 expression was decreased, but ChREBP was highly expressed in the renal tissue of DKD mice and HG-induced mouse mesangial cells (MMCs). miR-1225-3p could target and regulate the transcription of ARHGAP5, and an association between ARHGAP5 and SMURF2 was revealed. miR-1225-3p facilitated fibrosis and oxidative stress in MCCs by inhibiting ARHGAP5. In addition, SMURF2 promoted the ubiquitination of HA-ChREBP, and miR-1225-3p facilitated fibrosis and oxidative stress by mediating the ARHGAP5/SMURF2-mediated ubiquitination of ChREBP in MCCs. Furthermore, the miR-1225-3p inhibitor inhibited fibrosis and inflammation in the renal tissues of DKD mice.

Conclusion: miR-1225-3p facilitates fibrosis and oxidative stress by mediating ARHGAP5/SMURF2-mediated ubiquitination of ChREBP.

Background: This study aimed to develop and validate a nomogram for predicting acute kidney injury (AKI) in elderly patients in the intensive care unit (ICU).

Methods: Population data regarding elderly patients in ICU were derived from the Medical Information Mart for Intensive Care IV database from 2008 to 2019. The nomogram model was constructed from the training set using LASSO regression and logistic regression analysis, and the performance of the model was evaluated by decision curve analysis, calibration curve, and receiver operating characteristic (ROC) curve.

Results: According to inclusion and exclusion criteria, 14,373 elderly ICU patients were studied, of which 10,061 (70%) were assigned to the training set, and 4,312 (30%) were allocated to the validation set. Multivariate logistic analysis revealed that age, weight, myocardial infarction, congestive heart failure, dementia, diabetes, paraplegia, cancer, sepsis, body temperature, blood urea nitrogen, mechanical ventilation, urine volume, Sequential Organ Failure Assessment (SOFA) score, and Simplified Acute Physiology Score II (SAPS II) were independent risk factors for AKI in elderly ICU patients. The AUC values for the 15-factor nomogram were 0.812 (95% CI 0.802-0.822) and 0.802 (95% CI 0.787-0.818) in the training and validation sets, respectively. For clinical application, a simplified nomogram was constructed, which included age, weight, urine volume, SOFA score, and SAPS II, with the AUCs of 0.780 (95% CI 0.769-0.790) and 0.776 (95% CI 0.760-0.793), respectively. Calibration curve and decision curve analyses confirmed the models' high prediction accuracy and clinical value.

Conclusions: The nomogram developed in this study shows excellent predictive performance for AKI in elderly patients in the ICU.

Background: Cisplatin (CP) has been used as an effective chemotherapy drug for different types of cancers. Despite its therapeutic benefits, the clinical utility of CP is often hindered by adverse effects, notably acute kidney injury (AKI), which restricts its widespread application. Dihydromyricetin (DHM) is a flavonoid acquired from Ampelopsis grossedentata, exhibiting a range of pharmacological activities. The major objective of this research was to examine the possible molecular mechanism involved in CP-induced AKI and the protective function of DHM.

Methods: In this study, the protective function of DHM against CP-induced AKI was assessed in both mice and HK-2 cells. Kidney dysfunction parameters and renal morphology were evaluated to ascertain the extent of protection. Additionally, proteomics techniques were employed to investigate the protective effect of DHM and elucidate the underlying molecular mechanisms involved in mitigating CP-induced AKI. In addition, protein levels of epidermal growth factor receptor (EGFR), p-EGFR, heat shock protein 27 (HSP27), p-HSP27, STAT3, and p-STAT3 in renal tissues were investigated. Furthermore, an EGFR-blocking agent (gefitinib) or si-RNA of HSP27 was used to study the effects of inhibiting EGFR or HSP27 on CP-induced renal injury.

Results: DHM decreased blood urea nitrogen (BUN) and creatinine in serum, alleviated renal morphological injury and downregulated the expression of CP-induced kidney injury molecule-1 and neutrophil gelatinase-related lipocalin. Proteomic data revealed HSP27 as a potential therapeutic target for AKI. DHM treatment resulted in the downregulation of EGFR, HSP27, and STAT3 phosphorylation, ultimately mitigating CP-induced AKI. In addition, the inhibition of EGFR or HSP27 reduced mitochondria-mediated apoptosis and CP-induced cell damage in HK-2 cells.

Conclusions: DHM effectively inhibited CP-induced oxidative stress, inflammation, and mitochondria-mediated apoptosis through the EGFR/HSP27/STAT3 pathway.

Background: 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.

Methods: 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.

Results: 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 (p = 0.008) and also greater in the non-dialysis population compared to the dialysis population (p < 0.001). The median onset time was shorter in the dialysis population than in the non-dialysis population (days: 27 vs. 47, p = 0.016).

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.