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Microglial reactivity to injury and disease is emerging as a heterogeneous, dynamic, and crucial determinant in neurological disorders. However, the plasticity and fate of disease-associated microglia (DAM) remain largely unknown. We established a lineage tracing system, leveraging the expression dynamics of secreted phosphoprotein 1ï¼Spp1ï¼ to label and track DAM-like microglia during brain injury and recovery. Fate mapping of Spp1+ microglia during stroke in juvenile mice revealed an irreversible state of DAM-like microglia that were ultimately eliminated from the injured brain. By contrast, DAM-like microglia in the neonatal stroke models exhibited high plasticity, regaining a homeostatic signature and integrating into the microglial network after recovery. Furthermore, neonatal injury had a lasting impact on microglia, rendering them intrinsically sensitized to subsequent immune challenges. Therefore, our findings highlight the plasticity and innate immune memory of neonatal microglia, shedding light on the fate of DAM-like microglia in various neuropathological conditions.
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Lesiones Encefálicas , Accidente Cerebrovascular , Animales , Ratones , Microglía , Encéfalo/metabolismo , Osteopontina/metabolismoRESUMEN
Acute kidney injury (AKI) is a clinical condition characterized by a rapid decline in kidney function, which is associated with local inflammation and programmed cell death in the kidney. The G protein-coupled receptors (GPCRs) represent the largest family of signaling transduction proteins in the body, and approximately 40% of drugs on the market target GPCRs. The expressions of various GPCRs, prostaglandin receptors and purinergic receptors, to name a few, are significantly altered in AKI models. And the role of GPCRs in AKI is catching the eyes of researchers due to their distinctive biological functions, such as regulation of hemodynamics, metabolic reprogramming, and inflammation. Therefore, in this review, we aim to discuss the role of GPCRs in the pathogenesis of AKI and summarize the relevant clinical trials involving GPCRs to assess the potential of GPCRs and their ligands as therapeutic targets in AKI and the transition to AKI-CKD.
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Lesión Renal Aguda , Receptores Acoplados a Proteínas G , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Animales , Transducción de SeñalRESUMEN
BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.
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Fallo Renal Crónico , Diálisis Peritoneal , Peritonitis , Humanos , Femenino , Estudios Prospectivos , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversos , Hemoglobinas , Fallo Renal Crónico/epidemiología , Peritonitis/etiología , Estudios RetrospectivosRESUMEN
PURPOSE: The association between vitamin E and the risk of kidney disease is well documented in observational studies, but the role of vitamin E in kidney disease remain inconclusive. Here, we evaluated the causal effect of vitamin E on the risk of multiple kidney diseases, including chronic kidney disease, membranous nephropathy, diabetic nephropathy, IgA nephropathy, and dialysis. METHODS: We conducted a two-sample Mendelian randomization analysis from large-scale trans-ancestry genome-wide association studies to determine whether there was a significant causal relationship between vitamin E and multiple kidney diseases in European, American, and Asian ancestry. Instrumental genetic variants associated with vitamin E were selected, and summary statistic-based methods of inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode methods were conducted. Pleiotropy and sensitivity were assessed. RESULTS: We obtained 87 instrumental genetic variants in European ancestry and found no causal relationship between vitamin E and chronic kidney disease, membranous nephropathy, diabetic nephropathy, IgA nephropathy, and dialysis with no heterogeneity and pleiotropy. We obtained 18 instrumental genetic variants in Asian ancestry and vitamin E had no causal relationship with membranous nephropathy, diabetic nephropathy, and IgA nephropathy with no heterogeneity and pleiotropy. In African ancestry, 25 instrumental genetic variants were obtained and no causal relationship was identified with no heterogeneity and pleiotropy. CONCLUSION: Our study first suggested plausible non-causal associations between vitamin E and multiple kidney diseases among different ancestry.
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INTRODUCTION: Continuous Renal Replacement Therapy (CRRT) is a prolonged continuous extracorporeal blood purification therapy to replace impaired renal function. Typically, CRRT therapy requires routine anticoagulation, but for patients at risk of bleeding and with contraindications to sodium citrate, anticoagulant-free dialysis therapy is necessary. However, this approach increases the risk of CRRT circuit coagulation, leading to treatment interruption and increased resource consumption. In this study, we utilized artificial intelligence machine learning methods to predict the risk of CRRT circuit coagulation based on pre-CRRT treatment metrics. METHODS: We retrospectively analyzed 212 patients who underwent anticoagulant-free CRRT from October 2022 to October 2023. Patients were categorized into high-risk and low-risk groups based on CRRT circuit coagulation within 24 hours. We employed eight machine learning methods to predict the risk of circuit coagulation. The performance of the model was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC). 5-fold cross-validation was used to validate the machine learning models. Feature importance and SHAP plots were used to interpret the model's performance and key drivers. RESULTS: We identified 88 patients (41.51%) at high risk of circuit coagulation within 24 hours of CRRT. Our machine learning models showed excellent predictive performance, with ensemble learning (EL) achieving an AUC of 0.863 (95% CI 0.860 - 0.868), outperforming individual algorithms. Random forest (RF) was the best single-algorithm model, with an AUC of 0.819(95% CI 0.814 - 0.823). The top three features identified as most important by the SHAP summary plot and feature importance graph are platelet, FF, and triglycerides. CONCLUSION: We created a model using machine learning to predict the risk of circuit coagulation during anticoagulant-free CRRT therapy. Our model performs well (AUC 0.863) and identifies key factors like platelets, filtration fraction, and triglycerides. This facilitates the development of personalized treatment strategies by clinicians, aimed at reducing circuit coagulation risk, thereby enhancing patient outcomes and reducing healthcare expenses.
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The protein composition of human milk plays a crucial role in infant formula milk powder formulation. Notably, significant differences exist between bovine casein and human milk casein. Previous studies have shown that casein hydrolysates could enhance immune function; however, gastrointestinal dyspepsia in infants affects the type and function of peptides. Therefore, the present study used peptidomics to sequence and analyze hydrolyzed peptides from different casein fractions. Additionally, animal experiments were conducted to assess the functionality of these casein fractions and elucidate their differences. The results revealed variations in peptide composition among the different casein fractions of formula milk powder. Interestingly, milk powder formulated with both ß- and κ-casein (BK) exhibited significant enrichment of peptides related to the immune system. Moreover, the BK group significantly alleviated immune organ damage in cyclophosphamide-treated mice and regulated serum levels of pro-inflammatory and anti-inflammatory factors. Furthermore, feeding different casein fractions influenced the intestinal microflora of cyclophosphamide-treated mice, with the BK group mitigating the changes caused by cyclophosphamide. In conclusion, the findings suggest that BK formula in milk powder has the potential to positively enhance immunity. This study provides a robust theoretical basis for human-emulsified formula milk powder development.
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Caseínas , Leche Humana , Humanos , Lactante , Animales , Bovinos , Ratones , Caseínas/metabolismo , Polvos/análisis , Leche Humana/metabolismo , Péptidos/farmacología , Péptidos/análisis , Leche/químicaRESUMEN
BACKGROUND: We aimed to compare the cardiovascular events and mortality in patients who underwent either physician-oriented or patient-oriented kidney replacement therapy (KRT) conversion due to discontinuation of peritoneal dialysis (PD). METHODS: Patients with end-stage kidney disease who were receiving PD and required a switch to an alternative KRT were included. They were divided into physician-oriented group or patient-oriented group based on the decision-making process. Logistic regression analysis was used to explore the influencing factors related to KRT conversion in PD patients. The association of physician-oriented or patient-oriented KRT conversion with outcomes after the conversion was assessed by using Cox proportional hazards models. RESULTS: A total of 257 PD patients were included in the study. The median age at catheterization was 35 years. 69.6% of the participants were male. The median duration of PD was 20 months. 162 participants had patient-oriented KRT conversion, while 95 had physician-oriented KRT conversion. Younger patients, those with higher education levels, higher income, and no diabetes were more likely to have patient-oriented KRT conversion. Over a median follow-up of 39 months, 40 patients experienced cardiovascular events and 16 patients died. Physician-oriented KRT conversion increased nearly 3.8-fold and 4.0-fold risk of cardiovascular events and death, respectively. After adjusting for confounders, physician-oriented KRT conversion remained about a 3-fold risk of cardiovascular events. CONCLUSION: Compared to patient-oriented KRT conversion, PD patients who underwent physician-oriented conversion had higher risks of cardiovascular events and all-cause mortality. Factors included age at catheterization, education level, annual household income, and history of diabetes mellitus.
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Enfermedades Cardiovasculares , Fallo Renal Crónico , Diálisis Peritoneal , Humanos , Masculino , Adulto , Femenino , Terapia de Reemplazo Renal/efectos adversos , Diálisis Peritoneal/efectos adversos , Factores de Riesgo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/terapia , Enfermedades Cardiovasculares/complicaciones , Diálisis Renal/efectos adversosRESUMEN
After acute kidney injury (AKI), renal tubular epithelial cells (RTECs) are pathologically characterized by intracellular lipid droplet (LD) accumulation, which are involved in RTEC injury and kidney fibrosis. However, its pathogenesis remains incompletely understood. The protein, αKlotho, primarily expressed in RTECs, is well known as an anti-aging hormone wielding versatile functions, and its membrane form predominantly acts as a co-receptor for fibroblast growth factor 23. Here, we discovered a connection between membrane αKlotho and intracellular LDs in RTECs. Fluorescent fatty acid (FA) pulse-chase assays showed that membrane αKlotho deficiency in RTECs, as seen in αKlotho homozygous mutated (kl/kl) mice or in mice with ischemia-reperfusion injury (IRI)-induced AKI, inhibited FA mobilization from LDs by impairing adipose triglyceride lipase (ATGL)-mediated lipolysis and lipophagy. This resulted in LD accumulation and FA underutilization. IRI-induced alterations were more striking in αKlotho deficiency. Mechanistically, membrane αKlotho deficiency promoted E3 ligase peroxin2 binding to ubiquitin-conjugating enzyme E2 D2, resulting in ubiquitin-mediated degradation of ATGL which is a common molecular basis for lipolysis and lipophagy. Overexpression of αKlotho rescued FA mobilization by preventing ATGL ubiquitination, thereby lessening LD accumulation and fibrosis after AKI. This suggests that membrane αKlotho is indispensable for the maintenance of lipid homeostasis in RTECs. Thus, our study identified αKlotho as a critical regulator of lipid turnover and homeostasis in AKI, providing a viable strategy for preventing tubular injury and the AKI-to-chronic kidney disease transition.
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Accumulating evidence highlights mitochondrial dysfunction as a crucial factor in the pathogenesis of acute kidney injury (AKI); thus, novel therapeutic strategies maintaining mitochondrial homeostasis are highly anticipated. Recent studies have shown that cobaltosic oxide has peroxidase-like catalytic activities, although its role and mechanism remain elusive in AKI. In the present study, we synthesized and identified cobaltosic oxide-polyethylene glycol-triphenylphosphine (COPT) nanoparticles by conjugating cobaltosic oxide with polyethylene glycol and triphenylphosphine, to improve its biocompatibility and mitochondria-targeting property. We found that COPT preferentially accumulated in the kidney proximal tubule cells, and significantly alleviated ischemic AKI in mouse models and gentamicin induced-AKI in the zebrafish model. COPT also inhibited the transition from AKI to chronic kidney disease (CKD), with few side effects. Further studies demonstrated that COPT localized in the mitochondria, and ameliorated hypoxia-reoxygenation-mediated mitochondrial damage through enhancing mitophagy in vitro and in vivo. Mechanistically, COPT dose-dependently induced the expression of Bcl-2/adenovirus E1B 19-kDa interacting protein (BNIP3), while knockdown of BNIP3 attenuated COPT-induced mitophagic flux and mitochondrial protection. Thus, our findings suggest that COPT nanoparticles ameliorate AKI and its progression to CKD through inducing BNIP3-mediated mitophagy, indicating that COPT may serve as a promising mitochondria-targeting therapeutic agent against AKI.
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Lesión Renal Aguda , Insuficiencia Renal Crónica , Ratones , Animales , Mitofagia , Pez Cebra/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Lesión Renal Aguda/patología , Proteínas Mitocondriales/metabolismo , Proteínas de la Membrana/metabolismoRESUMEN
OBJECTIVES: Malnutrition is associated with adverse outcomes in acute or chronic diseases. However, the prediction value of the Geriatric Nutritional Risk Index (GNRI) in critically ill patients with acute kidney injury (AKI) has not been well studied. METHODS: Data was extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) and the electronic intensive care unit database. We used two nutritional indicators, the GNRI and the modified Nutrition Risk in Critically ill (NUTRIC) score, to evaluate the relationship between the nutritional status of patients with AKI and prognosis. The outcome is in-hospital mortality and 90-day mortality. The prediction accuracy of GNRI was compared with the NUTRIC score. RESULTS: A total of 4,575 participants with AKI were enrolled in this study. The median age of 68 (interquartile range, 56-79) years, and 1,142 (25.0%) patients experienced in-hospital mortality, and 1,238 (27.1%) patients experienced 90-day mortality. Kaplan-Meier survival analysis indicated that lower GNRI levels and high NUTRIC score are associated with lower in-hospital and 90-day survival of patients with AKI (P < .001 by log-rank test). After multivariate adjustment, Cox regression analysis demonstrated a 2-fold increased risk of in-hospital (hazard ratio = 2.019, 95% confidence interval: 1.699-2.400, P < .001) and 90-day (hazard ratio = 2.023, 95% confidence interval: 1.715-2.387, P < .001) mortality in the low GNRI group. Moreover, the multivariate-adjusted Cox model containing GNRI had higher prediction accuracy for the prognosis of patients with AKI than that with NUTRIC score (AUCGNRI model vs. AUCNUTRIC model for in-hospital mortality = 0.738 vs. 0.726, AUCGNRI model vs. AUCNUTRIC model for 90-day mortality = 0.748 vs. 0.726). In addition, the prediction value of GNRI was validated by the electronic intensive care unit database (7,881 patients with AKI) with satisfying performance (AUCGNRI model = 0.680). CONCLUSIONS: Our results demonstrated that GNRI is strongly associated with survival in patients in the intensive care unit coexisting with AKI, and the GNRI has a superior predictive value than the NUTRIC score.
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Lesión Renal Aguda , Desnutrición , Humanos , Anciano , Lactante , Evaluación Nutricional , Enfermedad Crítica , Estado Nutricional , Desnutrición/complicaciones , Factores de Riesgo , Estudios de Cohortes , Lesión Renal Aguda/complicaciones , Evaluación Geriátrica/métodos , Estudios RetrospectivosRESUMEN
PURPOSE: Little is known about the effect of visit-to-visit ultrafiltration volume (UV) variability on the outcome. In this study, we investigated the association between visit-to-visit UV variability and all-cause mortality in patients receiving hemodialysis (HD). METHODS: We consecutively enrolled patients who received maintenance HD in our center from March 2015 to March 2021. UV variability was defined using standard deviation (UVSD) and coefficient of variation (UVCV) (standard deviation divided by the mean). The relationship between UV variability and all-cause mortality was assessed using univariate and multivariate Cox proportional hazard regression models. Receiver operating characteristic curves were used to evaluate the predictive abilities of UVSD and UVCV for short-term and long-term survival rates. RESULTS: A total of 283 HD patients were included. The mean age was 57.54 years, and 53% were males. Follow-up was done for a median of 3.38 years (IQR 1.83-4.78). During the follow-up period, 73 patients died. Cox proportional hazards models indicated that UVSD and UVCV (higher versus lower) were positively associated with all-cause mortality (p=.003 and p<.001, respectively), while in multivariable-adjusted models, only higher UVCV remained significantly associated with all-cause mortality in patients receiving HD (HR 2.55 (95% CI 1.397-4.654), p=.002). Moreover, subgroup analyses showed that the predictive performance of UVCV was more accurate among older patients, males and patients with comorbidities. CONCLUSIONS: Visit-to-visit UV variability, especially UVCV, is a helpful indicator for predicting all-cause mortality in patients receiving HD, especially for older patients, males and those with comorbidities.
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Diálisis Renal , Ultrafiltración , Masculino , Humanos , Persona de Mediana Edad , Femenino , Diálisis Renal/efectos adversos , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
OBJECTIVE: To report the clinical and genetic characteristics of a rare case of Gitelman syndrome with comorbid Graves disease and ACTH-independent adrenocortical adenoma. METHODS: A patient who had presented at the Nanchong Central Hospital on December 21, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole-exome sequencing was carried out on DNA extracted from peripheral venous blood samples from the patient and her family members. RESULTS: The patient, a 45-year-old woman, was found to have Graves disease, ACTH-independent Cushing syndrome, hypokalemia and hypomagnesemia following the discovery of an adrenal incidentaloma. MRI scan had revealed a 3.8 cm × 3.2 cm mass in the left adrenal gland. The mass was removed by surgery and confirmed as adrenocortical adenoma. DNA sequencing revealed that the patient and her sister have both harbored compound heterozygous variants of the SLC12A3 gene, namely c.1444-10(IVS11)G>A and c.179(exon1)C>T (p.T60M), which were respectively inherited from their father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1444-10(IVS11)G>A and c.179(exon1)C>T (p.T60M) were respectively classified as a variant of uncertain significance (PM2_Supporting+PP3) and a likely pathogenic variant (PM3_Strong+PM1+PP3). CONCLUSION: The conjunction of Gitelman syndrome with Graves disease and adrenal cortex adenoma is rather rare. The newly discovered c.1444-10(IVS11)G>A variant of the SLC12A3 gene, together with the heterozygous variant of c.179(exon1)C>T (p.T60M), probably underlay the pathogenesis in this patient.
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Adenoma Corticosuprarrenal , Síndrome de Gitelman , Enfermedad de Graves , Hipopotasemia , Humanos , Femenino , Persona de Mediana Edad , Síndrome de Gitelman/genética , Enfermedad de Graves/genética , Madres , Mutación , Miembro 3 de la Familia de Transportadores de Soluto 12RESUMEN
Objective: To investigate the role and mechanism of trimethylamine N-oxide (TMAO), a uremic toxin, in renal fibrosis. Methods: A total of 20 male BALB/c mice were randomly and evenly assigned to a Control group and a TMAO group. Mice in the Control group received intraperitoneal injection of normal saline, while mice in the TMAO group received intraperitoneal injection of TMAO (20 mg/[kg·d]). The injection was given once a day for 8 weeks. Histopathology and fibrosis of kidney were observed by H&E staining and Masson staining. Immunohistochemistry was performed to determine the levels of alpha smooth muscle actin (α-SMA), recombinant human fibronectin fragment (Fibronectin), and sterol-regulatory element binding protein 1 (SREBP1). Western blot was performed to determine α-SMA, SREBP1, phosphatidylinositol 3 kinase (PI3K), phospho-phosphatidylinositol 3 kinase (p-PI3K), protein kinase B (PKB, also known as AKT), and phospho-AKT (p-AKT) protein levels. HK2 cells were treated with SREBP1 small interfering RNA (siRNA) and PI3K/AKT inhibitor, respectively, and the reversal of the effects of TMAO was examined. Results: Animal experiments showed that, compared with the Control group, the mice treated with TMAO experienced pathological damage and fibrosis of the kidney tissue and the expression levels of fibrosis markers, α-SMA and Fibronectin, in the kidney were increased (all P<0.05). According to the findings from further investigation, the TMAO-treatment group showed increased expression of SREBP1 and an up-regulation of PI3K phosphorylation ratio and AKT phosphorylation ratio compared with those of the Control group (all P<0.05). Cell experiments produced results similar to those of the animal experiment. After siRNA interference with SREBP1 expression, the expression levels of fibrosis marker proteins decreased (P<0.05). Besides, the high expression of SREBP1 caused by TMAO was inhibited after HK2 cells were incubated with LY294002, a PI3K-AKT pathway inhibitor (P<0.05). Conclusion: TMAO may induce renal fibrosis by promoting the PI3K/AKT/SREBP1 pathway.
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Enfermedades Renales , Proteínas Proto-Oncogénicas c-akt , Masculino , Humanos , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasa , Fosfatidilinositol 3-Quinasas/metabolismo , Fibronectinas/metabolismo , Enfermedades Renales/inducido químicamente , Fibrosis , ARN Interferente PequeñoRESUMEN
Cu2 O is an ideal p-type material for photo-electrochemical (PEC) hydrogen evolution, although serious electron-hole recombination and photocorrosion restrict its further improvement for PEC activity. In this work, CeO2 nanoparticles (NPs) self-assemble on the surface of Cu2 O octahedra, thus successfully forming a Cu2 O/CeO2 structure in which p-n heterojunctions and micro-mesocrystals (m-MCs) work together. The optimum Cu2 O/CeO2 composite, without the use of any cocatalyst, exhibits a fivefold higher photocurrent density (4.63â mA cm-2 at 0â V vs. the reversible hydrogen electrode) than that of Cu2 O octahedra, which is better than most Cu2 O-based photocathodes without cocatalyst and even comparable with advanced Cu2 O-based photocathodes. The hydrogen production of the optimal Cu2 O/CeO2 (Faradaic efficiency of â¼100 %) is 17.5â times higher than that of pure Cu2 O octahedra, and the photocurrent shows almost no decay under the 12â h stability test. The delicately designed Cu2 O/CeO2 structure in this work provides reference and inspiration for the design of cathodes materials.
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INTRODUCTION: Telemedicine (TM) has shown to provide potential benefits on clinical outcomes in patients with chronic kidney disease but limited evidences published in the peritoneal dialysis (PD) population. This study aimed to explore the long-term effects of TM on the mortality and technique failure. METHODS: The Peritoneal Dialysis Telemedicine-assisted Platform Cohort Study (PDTAP Study) was conducted prospectively in 27 hospitals in China since 2016. Patient and practice data were collected through the doctor-end of the TM app (Manburs) for all participants. TM including self-monitoring records, on-line education materials, and real-time physician-patient contact was only performed for the patient-end users of the Manburs. The primary outcome was all-cause mortality. The secondary outcomes were cause-specific mortality and all-cause and cause-specific permanent transfer to hemodialysis. RESULTS: A total of 7,539 PD patients were enrolled between June 2016 and April 2019, with follow-up till December 2020. Patients were divided into two cohorts: TM group (39.1%) and non-TM group (60.9%). A propensity score was used to create 2,160 matched pairs in which the baseline covariates were well-balanced. There were significantly lower risks of all-cause mortality (HR 0.59 [0.51, 0.67], p < 0.001), CVD mortality (HR 0.59 [0.49, 0.70], p < 0.001), all-cause transfer to hemodialysis (0.57 [0.48, 0.67], p < 0.001), transfer to hemodialysis from PD-related infection (0.67 [0.51, 0.88], p = 0.003), severe fluid overload (0.40 [0.30, 0.55], p < 0.001), inadequate solute clearance (0.49 [0.26, 0.92], p = 0.026), and catheter-related noninfectious complications (0.41 [0.17, 0.97], p = 0.041) in the TM group compared with the non-TM group. CONCLUSION: This study indicated real-world associations between TM usage and reduction in patient survival and technique survival through a multicenter prospective cohort.
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Fallo Renal Crónico , Diálisis Peritoneal , Peritonitis , Telemedicina , Humanos , Fallo Renal Crónico/epidemiología , Estudios de Cohortes , Estudios Prospectivos , Diálisis Peritoneal/métodos , Peritonitis/epidemiología , Peritonitis/etiología , Estudios RetrospectivosRESUMEN
OBJECTIVE: Exercise, like daily walking, may improve overall health and impede progression of chronic kidney disease (CKD); however, no specific walking dose has been recommended for patients with CKD. We aimed to investigate the association between daily walking steps and health-related quality of life (HRQOL) in adults with CKD. DESIGN AND METHODS: The walking steps of patients with CKD were extracted from the We Run mobile application. Their average daily walking steps were calculated and subdivided into the low-, middle-, and high-level groups. HRQOL was assessed using the physical component summary (PCS) and mental component summary (MCS) of the MOS 36 Short Form Health Survey (SF-36). RESULTS: A total of 558 adults (50.5%, men) with an average age of 40.2 (±13.8) years were enrolled. The median daily step count was 7,404 steps. The daily walking step count demonstrated an inverse U-shaped relationship with the SF-36 and subscale scores. Participants with daily walking steps between 7,000 and 12,000 have the highest PCS (68.1 ± 12.2) and MCS scores (70.0 ± 19.5). The multiple linear regression model showed that compared with patients with a daily step count of 7,000 to 12,000, patients with a daily step count >12,000 had a significantly lower MCS score (P < .001), while patients with a daily step count <7,000 had significantly lower PCS (P < .001) and MCS scores (P = .034). Moreover, the multivariable logistic regression model showed that patients with a daily step count >12,000 had significantly lower mental health-related quality (odds ratio [OR], 2.188; 95% confidence interval [CI], 1.079-1.439 for low MCS), while those with a daily step count <7,000 had a significantly lower HRQOL than the 7,000 to 12,000 daily step count group (OR, 2.113; 95% CI, 1.203-3.711 for low PCS; OR, 2.099; 95% CI, 1.210-3.643 for low MCS). CONCLUSIONS: These findings suggest that daily walking steps between 7,000 and 12,000 are associated with high HRQOL in adults with CKD.
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Calidad de Vida , Insuficiencia Renal Crónica , Adulto , Masculino , Humanos , Femenino , Salud Mental , Caminata , Encuestas Epidemiológicas , Encuestas y CuestionariosRESUMEN
BACKGROUND: The relationship between arteriolar hyalinosis and renal progression in immunoglobulin A nephropathy (IgAN) is not fully understood. We aimed to investigate the clinicopathological features and outcomes of IgAN with or without arteriolar hyalinosis. METHODS: A total of 762 diagnosed with IgAN patients were retrospectively analyzed. We classified IgAN patients into two groups with or without arteriolar hyalinosis. Then, the clinicopathological characteristics of the two groups were compared. We used Kaplan-Meier survival analysis to compare the composite kidney outcome of the two groups and applied multivariate Cox regression analyses to test the association between arteriolar hyalinosis and composite kidney outcome. RESULTS: Overall, 412 (54.1%) patients had arteriolar hyalinosis, including 173 patients diagnosed with hypertension. IgAN patients with arteriolar hyalinosis were older and had higher proteinuria, urea, uric acid, and blood pressure, while lower eGFR than those without arteriolar hyalinosis. Subgroup analysis showed similar results in IgAN patients with hypertension. Kaplan-Meier survival analysis showed that IgAN patients with arteriolar hyalinosis had worse composite kidney outcome than those without arteriolar hyalinosis. In addition, subgroup analysis revealed that patients with hypertension have worse composite kidney outcome than those without hypertension. Multivariate Cox regression analyses confirm that arteriolar hyalinosis (HR 2.57; 95% CI 1.41-4.69; p = 0.002) is an independent risk factor for renal prognosis in IgAN patients. CONCLUSIONS: Our study demonstrated that arteriolar hyalinosis is a common vascular lesion in IgAN patients. Arteriolar hyalinosis connects closely with hypertension, and arteriolar hyalinosis is an independent risk factor for renal prognosis in patients with IgAN.
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Glomerulonefritis por IGA , Hipertensión , Arteriolas , Presión Sanguínea , Diarrea , Progresión de la Enfermedad , Enfermedades Hereditarias del Ojo , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/patología , Humanos , Hipertensión/complicaciones , Enfermedades Intestinales , Riñón/patología , Pronóstico , Estudios Retrospectivos , Anomalías Cutáneas , Enfermedades Vasculares/complicacionesRESUMEN
Although the key role of renal fibrosis in the progression of chronic kidney disease (CKD) is well known, the causes of renal fibrosis are not fully clarified. In this study, interferon regulatory factor 1 (IRF-1), a mammalian transcription factor, was highly expressed in fibrotic kidney of CKD patients. Concordantly, the expression level of IRF-1 was significantly elevated in the kidney of unilateral ureteral obstruction (UUO) and Adriamycin nephropathy (ADR) mice. In tubular epithelial cells, overexpression of IRF-1 could induce profibrotic markers expression, which accompanied by dramatic downregulation of Klotho, an important inhibitor of renal fibrosis. Luciferase reporter analysis and ChIP assay revealed that IRF-1 repressed Klotho expression by downregulation of C/EBP-ß, which regulates Klotho gene transcription via directly binding to its promoter. Further investigation showed that tumor necrosis factor-alpha may be an important inducement for the increase of IRF-1 in tubular epithelial cells after UUO and genetic deletion of IRF-1 attenuated renal fibrosis in UUO mice. Hence, these findings demonstrate that IRF-1 contributes to the pathogenesis of renal fibrosis by downregulation of Klotho, and suppresses IRF-1 may be a potential therapeutic target for CKD.
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Glucuronidasa/metabolismo , Factor 1 Regulador del Interferón/metabolismo , Riñón/metabolismo , Riñón/patología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Animales , Western Blotting , Línea Celular , Inmunoprecipitación de Cromatina , Glucuronidasa/genética , Células HEK293 , Humanos , Inmunoprecipitación , Factor 1 Regulador del Interferón/genética , Riñón/efectos de los fármacos , Proteínas Klotho , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Biológicos , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Necrosis Tumoral alfa/farmacología , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/patologíaRESUMEN
BACKGROUND: Alport syndrome (AS), which is a rare hereditary disease caused by mutations of genes including COL4A3, COL4A4 and COL4A5, has a wide spectrum of phenotypes. Most disease-causing variants of AS are located in the exons or the conservative splicing sites of these genes, while little is known about the intronic disease-causing variants. METHODS: A Chinese AS family was recruited in this study. All the clinical data of AS patient were collected from medical records. After pedigree analysis, the pathogenic variants were studied by the whole exome sequencing (WES). Minigene assay and in vivo RT-PCR analysis were performed to validate the functions of the variants. RESULTS: Renal biopsy showed a typical histopathology changes of AS. WES revealed compound heterozygous substitution, NM_033380 c.991-14(IVS17) A > G, in the intron 17 of the COL4A5 gene, which were confirmed by Sanger sequencing. Moreover, the variant was co-segregated with the phenotype in this family. Minigene assay in cultured cell lines showed that a splicing error was induced by this intronic variant, which further confirmed by in vivo RT-PCR analysis. CONCLUSION: A novel intronic disease-causing variant in COL4A5 gene was identified by WES, which was the molecular pathogenic basis of AS.
Asunto(s)
Colágeno Tipo IV/genética , Intrones/genética , Nefritis Hereditaria/genética , Pueblo Asiatico/genética , Niño , Femenino , Humanos , Mutación , Nefritis Hereditaria/diagnóstico por imagen , Nefritis Hereditaria/patología , Linaje , Reacción en Cadena en Tiempo Real de la Polimerasa , Secuenciación del ExomaRESUMEN
The incidence of cardiovascular thrombotic events which are highly associated with atherosclerotic plaque vulnerability and its rupture is much higher in chronic kidney disease (CKD) patients than that in the general population. It has been reported that the thinning of fibrous cap in atherosclerotic plaque is a crucial factor in plaque vulnerability and thrombosis. Moreover, vascular smooth muscle cells (VSMCs) senescence play a crucial role in maintaining the thickness of fibrous cap. Lamin B1, one of the members of laminin family, is an important component of the nuclear membrane and it is related to cell senescence. While whether lamin B1 participates CKD-related VSMCs senescence and plaque vulnerability and the underlying mechanism remain unclear. Here, we found that CKD promoted fibrous cap thinning and reduced the stability of atherosclerotic plaque through accelerating VSMCs senescence. VSMCs senescence induced by CKD was related to the increased expression of lamin B1 and abnormality of nuclear membrane structure. Knocking down the expression of lamin B1 with RNA interference prevented CKD-induced aberrant nuclear membrane structure and senescence in VSMCs. Additionally, overproduction of reactive oxidative stress (ROS) and subsequent activation of ROS/p38MAPK under CKD milieus contribute to these series of outcomes, as scavenging ROS with N-acety-l-cysteine (NAC) or inhibiting p38MAPK signal pathway with SB203580 could inhibit CKD-induced activation of ROS/p38MAPK, increased expression of lamin B1, abnormality of nuclear membrane structure and VSMCs senescence. Taken together, these results suggested that ROS/p38MAPK-mediated increased expression of lamin B1 and abnormality of nuclear membrane structure was an important mechanism of CKD-induced VSMCs senescence.