Renal Failure最新文献

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.

Background: Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease globally. Recent research has identified insulin-like growth factor-binding proteins 2 (IGFBP2) and 4 (IGFBP4) as potential biomarkers for DKD. Overactivation of the complement pathway in DKD remains poorly understood.

Methods: Blood samples were collected from patients for proteomic analysis, complemented by both in vitro and in vivo experiments to investigate the roles of IGFBP2, IGFBP4, and the complement pathway in DKD.

Results: Elevated levels of IGFBP2 and IGFBP4 were observed in DKD patients. The levels of IGFBP2 and IGFBP4 increased in DKD mice, accompanied by the activation of the complement pathway, and a deterioration in renal function. High glucose and serum from DKD mice stimulated an increase in the levels of IGFBP2 and IGFBP4 in HK-2 cells. The supernatant from HK-2 cells was used to culture THP-1 cells, resulted in an increase in the M1 type of THP-1 cells, a decrease in the M2 type, and activation of the complement pathway. The supernatant from THP-1 cells affected the growth of primary human renal podocytes. The exogenous addition of IGFBP2 and IGFBP4 proteins to primary human renal podocytes did not affect their growth. However, when human renal podocytes were cultured with the supernatant from THP-1 cells, the growth of the podocytes was affected.

Conclusions: IGFBP2 and IGFBP4 interact to stimulate the activation of the complement pathway in macrophages, which induces podocyte apoptosis and subsequently promotes the development of DKD.

Background: IgA nephropathy (IgAN) presents a challenging spectrum of outcomes, often complicated by intrarenal arterial/arteriolar lesions (IALs) in affected individuals. Despite their clinical relevance, existing criteria for classifying and assessing the severity of these lesions remain undefined. This study aimed to establish semi-quantitative assessment criteria for grading IALs and to evaluate their prognostic significance in patients with IgAN.

Method: We conducted a retrospective cohort study of 417 cases of primary IgAN in which IALs were meticulously scored in individual biopsies. Kaplan-Meier survival analysis was employed to compare the time to the renal composite endpoint between different IALs severity groups. The association between the severity of IALs and clinical outcomes was further evaluated using multivariate Cox regression models to control for potential confounders.

Results: Among the 417 patients studied, 230 (55.2%) exhibited IALs. Kaplan-Meier curve analysis showed a higher cumulative incidence of the composite endpoint in patients with IALs (p < 0.001). In a compelling multivariate analysis, we identified IALs and its subclassifications, including moderate to severe intimal fibrosis and hyalinosis, as strong independent risk factors for poor prognosis (IALs: HR = 2.15, p = 0.009; moderate to severe hyalinosis: HR = 3.58, p = 0.001; moderate to severe intimal fibrosis: HR = 3.56, p = 0.001).

Conclusion: Our findings underscore the prognostic significance of IALs in IgAN, particularly moderate to severe intimal fibrosis and hyalinosis and highlight the urgent need for novel therapeutic strategies specifically designed to mitigate the impact of IALs in high-risk IgAN patients.

Background: In patients undergoing hemodialysis (HD), cardiovascular (CV) disease, particularly sudden cardiac death (SCD), is a major cause of mortality. Independent predictors of SCD include a prolonged QT interval on electrocardiography (ECG) and elevated levels of natriuretic peptides (NPs). This study explores the association between the QTc interval and NPs in HD patients.

Methods: This cross-sectional study involved 207 HD patients, having a heart rate of 57 to 103 bpm, displaying sinus rhythm and no extrasystoles in ECG reports. Before the 2nd HD of the week, we conducted ECG and blood tests for atrial NP (ANP), brain NP (BNP), and N-terminal proBNP (NT-proBNP). The heart rate-corrected QT (QTc) was calculated using Bazett formula. Our analysis focused on the association between QTc and each NP, along with evaluating clinically relevant variables related to the QTc interval.

Results: Univariate analyses indicated robust correlations among the NPs, with each NP significantly associated with the QTc interval. Multiple regression analyses of the three NPs revealed that NT-proBNP demonstrated the strongest predictive ability for the QTc interval. Independent predictors of prolonged QTc included lower corrected calcium (cCa) levels (p = 0.001), lower potassium (K) levels (p < 0.001), and higher log NT-proBNP (p = 0.004).

Conclusion: In HD patients, NT-proBNP shows a stronger link with the QTc interval than BNP or ANP. Integrating clinical management considering both QTc and log NT-proBNP levels might help reduce CV events. Additionally, vigilance regarding low K or cCa levels is recommended from the perspective of the QTc interval.

Background: Both sleep disorders and chronic kidney disease (CKD) are recognized as significant public health concerns. In the general population, sleep disorders have been shown to be associated with frailty in the elderly. This study aims to evaluate the association between sleep duration and trouble sleeping with frailty in CKD patients, as well as the potential interactive effect between these two factors.

Methods: This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005-2018. Sleep duration and trouble sleeping was self-reported. Frailty was assessed using a 49-item frailty index. The associations between sleep duration, trouble sleeping, and frailty were analyzed using weighted multivariate logistic regression and restricted cubic splines. Subgroup analysis was conducted to determine the consistency of the study's conclusions across various subgroups.

Results: A total of 5,211 adult CKD patients were included in this analysis. Regression analysis results indicated that short sleep duration (OR = 1.364, 95% CI: 1.152-1.616), long sleep duration (OR = 1.648, 95% CI: 1.259-2.157), and trouble sleeping (OR = 2.572, 95% CI: 2.102-3.147) were significantly associated with an increased risk of frailty in CKD patients, with an interaction between sleep duration and trouble sleeping. Subgroup analysis revealed that the effects of trouble sleeping and sleep duration on frailty symptoms in CKD patients exhibit significant variation across age groups (p < 0.05 for interaction), with no notable differences observed in other subgroups. RCS results demonstrated a U-shaped relationship between frailty and sleep duration, with the lowest risk of frailty at 7.12 h of sleep.

Conclusion: Our findings indicated that both sleep duration and trouble sleeping were significantly associated with frailty in CKD patients, with a notable interaction between these two factors. Therefore, prevention and intervention strategies for frailty in CKD patients should address multiple aspects of sleep health.