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Elucidating the regulatory mechanisms of human adipose tissues (ATs) evolution is essential for understanding human-specific metabolic regulation, but the functional importance and evolutionary dynamics of three-dimensional (3D) genome organizations of ATs are not well defined. Here, we compared the 3D genome architectures of anatomically distinct ATs from humans and six representative mammalian models. We recognized evolutionarily conserved and human-specific chromatin conformation in ATs at multiple scales, including compartmentalization, topologically associating domain (TAD), and promoter-enhancer interactions (PEI), which have not been described previously. We found PEI are much more evolutionarily dynamic with respect to compartmentalization and topologically associating domain. Compared to conserved PEIs, human-specific PEIs are enriched for human-specific sequence, and the binding motifs of their potential mediators (transcription factors) are less conserved. Our data also demonstrated that genes involved in the evolutionary dynamics of chromatin organization have weaker transcriptional conservation than those associated with conserved chromatin organization. Furthermore, the genes involved in energy metabolism and the maintenance of metabolic homeostasis are enriched in human-specific chromatin organization, while housekeeping genes, health-related genes, and genetic variations are enriched in evolutionarily conserved compared to human-specific chromatin organization. Finally, we showed extensively divergent human-specific 3D genome organizations among one subcutaneous and three visceral ATs. Together, these findings provide a global overview of 3D genome architecture dynamics between ATs from human and mammalian models and new insights into understanding the regulatory evolution of human ATs.
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Tejido Adiposo , Cromatina , Genoma , Animales , Humanos , Cromatina/genética , Ensamble y Desensamble de Cromatina , Genómica , Homeostasis , Mamíferos , Tejido Adiposo/metabolismoRESUMEN
BACKGROUND: Postoperative acute kidney injury (AKI) is a common condition after surgery, however, the available data about nationwide epidemiology of postoperative AKI in China from large and high-quality studies are limited. This study aimed to determine the incidence, risk factors and outcomes of postoperative AKI among patients undergoing surgery in China. METHODS: This was a large, multicentre, retrospective study performed in 16 tertiary medical centres in China. Adult patients (≥18 years of age) who underwent surgical procedures from 1 January 2013 to 31 December 2019 were included. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine criteria. The associations of AKI and in-hospital outcomes were investigated using logistic regression models adjusted for potential confounders. RESULTS: Among 520 707 patients included in our study, 25 830 (5.0%) patients developed postoperative AKI. The incidence of postoperative AKI varied by surgery type, which was highest in cardiac (34.6%), urologic (8.7%) and general (4.2%) surgeries. A total of 89.2% of postoperative AKI cases were detected in the first 2 postoperative days. However, only 584 (2.3%) patients with postoperative AKI were diagnosed with AKI on discharge. Risk factors for postoperative AKI included older age, male sex, lower baseline kidney function, pre-surgery hospital stay ≤3 days or >7 days, hypertension, diabetes mellitus and use of proton pump inhibitors or diuretics. The risk of in-hospital death increased with the stage of AKI. In addition, patients with postoperative AKI had longer lengths of hospital stay (12 versus 19 days) and were more likely to require intensive care unit care (13.1% versus 45.0%) and renal replacement therapy (0.4% versus 7.7%). CONCLUSIONS: Postoperative AKI was common across surgery type in China, particularly for patients undergoing cardiac surgery. Implementation and evaluation of an alarm system is important for the battle against postoperative AKI.
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Lesión Renal Aguda , Complicaciones Posoperatorias , Humanos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/epidemiología , Masculino , Femenino , China/epidemiología , Incidencia , Estudios Retrospectivos , Factores de Riesgo , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anciano , Adulto , Mortalidad HospitalariaRESUMEN
SIGNIFICANCE STATEMENT: Serum creatinine is not a sensitive biomarker for neonatal AKI because it is confounded by maternal creatinine level, gestational age, and neonatal muscle mass. In this multicenter cohort study of 52,333 hospitalized Chinese neonates, the authors proposed serum cystatin C-related criteria (CyNA) for neonatal AKI. They found that cystatin C (Cys-C) is a robust and sensitive biomarker for identifying AKI in neonates who are at an elevated risk of in-hospital mortality and that CyNA detects 6.5 times as many cases as the modified Kidney Disease Improving Global Outcomes creatinine criteria. They also show that AKI can be detected using a single test of Cys-C. These findings suggest that CyNA shows promise as a powerful and easily applicable tool for detecting AKI in neonates. BACKGROUND: Serum creatinine is not a sensitive biomarker for AKI in neonates. A better biomarker-based criterion for neonatal AKI is needed. METHODS: In this large multicenter cohort study, we estimated the upper normal limit (UNL) and reference change value (RCV) of serum cystatin C (Cys-C) in neonates and proposed cystatin C-based criteria (CyNA) for detecting neonatal AKI using these values as the cutoffs. We assessed the association of CyNA-detected AKI with the risk of in-hospital death and compared CyNA performance versus performance of modified Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. RESULTS: In this study of 52,333 hospitalized neonates in China, Cys-C level did not vary with gestational age and birth weight and remained relatively stable during the neonatal period. CyNA criteria define AKI by a serum Cys-C of ≥2.2 mg/L (UNL) or an increase in Cys-C of ≥25% (RCV) during the neonatal period. Among 45,839 neonates with measurements of both Cys-C and creatinine, 4513 (9.8%) had AKI detected by CyNA only, 373 (0.8%) by KDIGO only, and 381 (0.8%) by both criteria. Compared with neonates without AKI by both criteria, neonates with AKI detected by CyNA alone had an increased risk of in-hospital mortality (hazard ratio [HR], 2.86; 95% confidence interval [95% CI], 2.02 to 4.04). Neonates with AKI detected by both criteria had an even higher risk of in-hospital mortality (HR, 4.86; 95% CI, 2.84 to 8.29). CONCLUSIONS: Serum Cys-C is a robust and sensitive biomarker for detecting neonatal AKI. Compared with modified KDIGO creatinine criteria, CyNA is 6.5 times more sensitive in identifying neonates at elevated risk of in-hospital mortality.
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Lesión Renal Aguda , Cistatina C , Recién Nacido , Humanos , Estudios de Cohortes , Creatinina , Estudios Prospectivos , Mortalidad Hospitalaria , BiomarcadoresRESUMEN
BACKGROUND: The role of statin therapy in the development of kidney disease in patients with type 2 diabetes mellitus (DM) remains uncertain. We aimed to determine the relationships between statin initiation and kidney outcomes in patients with type 2 DM. METHODS: Through a new-user design, we conducted a multicentre retrospective cohort study using the China Renal Data System database (which includes inpatient and outpatient data from 19 urban academic centres across China). We included patients with type 2 DM who were aged 40 years or older and admitted to hospital between Jan. 1, 2000, and May 26, 2021, and excluded those with pre-existing chronic kidney disease and those who were already on statins or without follow-up at an affiliated outpatient clinic within 90 days after discharge. The primary exposure was initiation of a statin. The primary outcome was the development of diabetic kidney disease (DKD), defined as a composite of the occurrence of kidney dysfunction (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and > 25% decline from baseline) and proteinuria (a urinary albumin-to-creatinine ratio ≥ 30 mg/g and > 50% increase from baseline), sustained for at least 90 days; secondary outcomes included development of kidney function decline (a sustained > 40% decline in eGFR). We used Cox proportional hazards regression to evaluate the relationships between statin initiation and kidney outcomes, as well as to conduct subgroup analyses according to patient characteristics, presence or absence of dyslipidemia, and pattern of dyslipidemia. For statin initiators, we explored the association between different levels of lipid control and outcomes. We conducted analyses using propensity overlap weighting to balance the participant characteristics. RESULTS: Among 7272 statin initiators and 12 586 noninitiators in the weighted cohort, statin initiation was associated with lower risks of incident DKD (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62-0.83) and kidney function decline (HR 0.60, 95% CI 0.44-0.81). We obtained similar results to the primary analyses for participants with differing patterns of dyslipidemia, those prescribed different statins, and after stratification according to participant characteristics. Among statin initiators, those with intensive control of high-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L) had a lower risk of incident DKD (HR 0.51, 95% CI 0.32-0.81) than those with inadequate lipid control (LDL-C ≥ 3.4 mmol/L). INTERPRETATION: For patients with type 2 DM admitted to and followed up in academic centres, statin initiation was associated with a lower risk of kidney disease development, particularly in those with intensive control of LDL-C. These findings suggest that statin initiation may be an effective and reasonable approach for preventing kidney disease in patients with type 2 DM.
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Diabetes Mellitus Tipo 2 , Dislipidemias , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Insuficiencia Renal Crónica , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , LDL-Colesterol , Estudios Retrospectivos , Insuficiencia Renal Crónica/epidemiología , Dislipidemias/tratamiento farmacológico , Dislipidemias/epidemiologíaRESUMEN
Uromodulin (Umod, Tamm-Horsfall protein) is the most abundant urinary N-glycoprotein produced exclusively by the kidney. It can form filaments to antagonize the adhesion of uropathogens. However, the site-specific N-glycosylation signatures of Umod in healthy individuals and patients with IgA nephropathy (IgAN) remain poorly understood due to the lack of suitable isolation and analytical methods. In this study, we first presented a simple and fast method based on diatomaceous earth adsorption to isolate Umod. These isolated glycoproteins were digested by trypsin and/or Glu-C. Intact N-glycopeptides with or without HILIC enrichment were analyzed using our developed EThcD-sceHCD-MS/MS. Based on the optimized workflow, we identified a total of 780 unique intact N-glycopeptides (7 N-glycosites and 152 N-glycan compositions) from healthy individuals. As anticipated, these glycosites exhibited glycoform heterogeneity. Almost all N-glycosites were modified completely by the complex type, except for one N-glycosite (N275), which was nearly entirely occupied by the high-mannose type for mediating Umod's antiadhesive activity. Then, we compared the N-glycosylation of Umod between healthy controls (n = 9) and IgAN patients (n = 9). The N-glycosylation of Umod in IgAN patients will drastically decrease and be lost. Finally, we profiled the most comprehensive site-specific N-glycosylation map of Umod and revealed its alterations in IgAN patients. Our method provides a high-throughput workflow for characterizing the N-glycosylation of Umod, which can aid in understanding its roles in physiology and pathology, as well as serving as a potential diagnostic tool for evolution of renal tubular function.
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Application of long non-coding RNAs (lncRNAs) for modulation of breast cancer (BC) has attracted much attention. Here, we probed into the role and underlying mechanism of long intergenic non-coding RNA 01270 (LINC01270) in BC. With the help of bioinformatics tools, we identified laminin subunit alpha 2 (LAMA2) as a BC-related differentially expressed gene to discern the effect of LAMA2 in BC cells. LAMA2 was initially poorly expressed while LINC01270 was highly expressed in BC. BC cells were subsequently treated with sh-LINC01270 or/and sh-LAMA2 for exploration of their regulatory mechanism in BC, which unfolded that LINC01270 inhibition up-regulated LAMA2 and inactivated the MAPK signaling pathway to suppress malignant characteristics of BC cells. Functional assays demonstrated that LINC01270 bound to DNMT1, DNMT3a, and DNMT3b promoted the methylation of CpG islands in LAMA2 promoter and inhibited the LAMA2 expression. Moreover, our data suggested that LAMA2 suppressed MAPK signaling pathway to inhibit BC cell malignant characteristics. The in vitro results were re-produced with the help of the in vivo experimentations. In conclusion, LINC01270 silencing inhibited the methylation of LAMA2 promoter to suppress the activation of MAPK signaling pathway, which subsequently restrained the BC progression. 1, Overexpression of LAMA2 inhibits malignant features of BC cells. 2, LINC01270 promotes LAMA2 promoter methylation by recruiting DNMTs to the LAMA2 promoter region. 3, 5-aza-dc reverses the promotion of LAMA2 promoter methylation by LINC01270. 4, LAMA2 inhibits malignant features of BC cells by suppressing the activation of MAPK signaling pathway.
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Neoplasias de la Mama , ARN Largo no Codificante , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Epigénesis Genética/genética , Metilación de ADN/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transducción de Señal/genética , Regulación Neoplásica de la Expresión Génica/genética , Regiones Promotoras Genéticas/genética , Línea Celular TumoralRESUMEN
BACKGROUND At present, there are few blood pressure variability (BPV)-related studies of elderly maintenance hemodialysis (MHD) patients. This study aimed to compare the effects of long-term BPV on the 46-month survival rate of MHD patients aged <75 years and ≥75 years between 2000 and 2014, with follow-up until 2018. MATERIAL AND METHODS According to systolic blood pressure variability (SBPV) and diastolic blood pressure variability (DBPV), patients were divided into 4 groups: a low SBPV group (n=121), a high SBPV group (n=122), a low DBPV group (n=114), and a high DBPV group (n=112). RESULTS We included 243 patients in the study. All the patients were followed up for 46 months, and 59 patients (28 males) died during follow-up. The survival rate of patients in the high SBPV group was significantly lower than that of the low SBPV group (log rank P=0.049). No significant differences were observed between the high DBPV group and low DBPV group (log rank P=0.167). There were no significant differences in survival rates between the high SBPV group and low SBPV group among patients aged <75 years (log rank P=0.656), and among patients ≥75 years, the survival rate of the high SBPV group was significantly lower than that of the low SBPV group (log rank P=0.041). CONCLUSIONS Increased long-term SBPV in MHD patients is associated with a decrease in long-term survival rate, and patients ≥75 years are more susceptible to it.
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Monitoreo Ambulatorio de la Presión Arterial , Diálisis Renal , Masculino , Anciano , Humanos , Presión Sanguínea , Estudios de Seguimiento , Tasa de SupervivenciaRESUMEN
The kidney reabsorbs large amounts of glucose through Na+-glucose cotransporter 2 (SGLT2). P4-ATPase acts together with the ß-subunit TMEM30A to mediate the asymmetric distribution of phosphatidylserine (PS), phosphatidylethanolamine (PE), and other amino phospholipids, promoting plasma membrane and internal vesicle fusion, and facilitating vesicle protein transport. We observed reduced TMEM30A expression in renal tubules of DKD and IgA patients, suggesting a potential role of TMEM30A in renal tubular cells. To investigate the role of TMEM30A in renal tubules, we constructed a TMEM30A knockdown cell model by transfecting mouse kidney tubular epithelium cells (TCMK-1) with TMEM30A shRNA. Knockdown of TMEM30A in TCMK-1 cells attenuated vesicle transporter protein synthesis, resulting in reduced transport and expression of SGLT2, which in turn reduced glucose absorption. These data suggested that TMEM30A plays a crucial role in renal tubules.
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Túbulos Renales , Riñón , Animales , Ratones , Células Epiteliales , Glucosa , Transportador 2 de Sodio-GlucosaRESUMEN
PURPOSE: To evaluate the effects of magnesium (Mg) supplementation on vascular calcification (VC) in patients with chronic kidney disease (CKD). METHODS: PubMed, Embase, Cochrane Library, Medline, Web of Science, CNKI, VIP, and WanFang databases were searched from build to July 2022. Randomized controlled trials (RCT) and non-RCT related to whether Mg supplementation inhibits VC in patients with CKD were included. The literature was screened according to inclusion and exclusion criteria, and quality evaluation and data collection were performed. Meta-analysis was performed using Review Manager 5.4 software. RESULTS: 8 RCTs and 1 non-RCT studies with a total of 496 patients were eventually included. Compared to control groups, Mg supplementation increased serum Mg levels (SMD = 1.26, 95% CI: -0.70 to 1.82, p < 0.001), but it was not statistically significant in alleviating the degree of VC, increasing T50, and reducing serum phosphorus (P) levels in patients with CKD (all p > 0.05). Oral Mg reduced left (WMD=-0.06, 95% CI. -0.11 to -0.01, p = 0.03) and right (WMD=-0.07, 95% CI: -0.13 to -0.01, p = 0.02) carotid intima-media thickness (cIMT). Additionally, calcium (Ca) (SMD=-0.43, 95% CI: -0.74 to -0.11, p = 0.008) and parathyroid hormone (PTH) (SMD=-0.43, 95% CI: -0.75 to -0.11, p = 0.008) levels were reduced by increasing dialysate Mg concentration. CONCLUSIONS: Mg supplementation increased serum Mg levels and reduced Ca, PTH, and cIMT, but it did not reduce VC scores in patients with CKD. This still requires further studies with larger samples to evaluate the effect of Mg supplementation on VC.
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Insuficiencia Renal Crónica , Calcificación Vascular , Humanos , Magnesio , Calcificación Vascular/etiología , Calcificación Vascular/prevención & control , Soluciones para Diálisis , Calcio , Hormona Paratiroidea , Insuficiencia Renal Crónica/complicacionesRESUMEN
BACKGROUND: Primary membranous nephropathy (PMN) has a heterogeneous natural course. Immunosuppressive therapy is recommended for PMN patients at moderate or high risk of renal function deterioration. Prediction models for the treatment failure of PMN have rarely been reported. METHODS: This study retrospectively studied patients diagnosed as PMN by renal biopsy at Sichuan Provincial People's Hospital from January 2017 to December 2020. Information on clinical characteristics, laboratory test results, pathological examination, and treatment was collected. The outcome was treatment failure, defined as the lack of complete or partial remission at the end of 12 months. Simple logistic regression was used to identify candidate predictive variables. Forced-entry stepwise multivariable logistic regression was used to develop the prediction model, and performance was evaluated using C-statistic, calibration plot, and decision curve analysis. Internal validation was performed by bootstrapping. RESULTS: In total, 310 patients were recruited for this study. 116 patients achieved the outcome. Forced-entry stepwise multivariable logistic regression indicated that PLA2Rab titer (OR = 1.002, 95% CI: 1.001-1.004, p = 0.003), inflammatory cells infiltration (OR = 2.753, 95% CI: 1.468-5.370, p = 0.002) and C3 deposition on immunofluorescence (OR = 0.217, 95% CI: 0.041-0.964, p = 0.049) were the three independent risk factors for treatment failure of PMN. The final prediction model had a C-statistic (95% CI) of 0.653 (0.590-0.717) and a net benefit of 23%-77%. CONCLUSIONS: PLA2R antibody, renal interstitial inflammation infiltration, and C3 deposition on immunofluorescence were the three independent risk factors for treatment failure in PMN. Our prediction model might help identify patients at risk of treatment failure; however, the performance awaits improvement.
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Glomerulonefritis Membranosa , Humanos , Glomerulonefritis Membranosa/patología , Nomogramas , Estudios Retrospectivos , Autoanticuerpos , Insuficiencia del TratamientoRESUMEN
Objective: The pathogenesis of renal osteopathy and cardiovascular disease suggests the disordered bone-vessel axis in chronic kidney disease-mineral bone disorder (CKD-MBD). However, the mechanism of the bone-vessel axis in CKD-MBD remains unclear.Methods: We established a CKD-MBD rat model to observe the pathophysiological phenotype of the bone-vessel axis and performed RNA sequencing of aortas to identify novel targets of the bone-vessel axis in CKD-MBD.Results: The microarchitecture of the femoral trabecular bone deteriorated and alveolar bone loss was aggravated in CKD-MBD rats. The intact parathyroid hormone and alkaline phosphatase levels increased, 1,25-dihydroxyvitamin D3 levels decreased, and intact fibroblast growth factor-23 levels did not increase in CKD-MBD rats at 16 weeks; other bone metabolic parameters in the serum demonstrated dynamic characteristics. With calcium deposition in the abdominal aortas of CKD-MBD rats, RNA sequencing of the aortas revealed a significant decrease in inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) gene levels in CKD-MBD rats. A similar trend was observed in rat aortic smooth muscle cells. As a secretory protein, ITPR2 serum levels decreased at 4 weeks and slightly increased without statistical differences at 16 weeks in CKD-MBD rats. ITPR2 serum levels were significantly increased in patients with vascular calcification, negatively correlated with blood urea nitrogen levels, and positively correlated with serum tartrate-resistant acid phosphatase 5b levels.Conclusion: These findings provide preliminary insights into the role of ITPR2 in the bone-vessel axis in CKD-MBD. Thus, ITPR2 may be a potential target of the bone-vessel axis in CKD-MBD.
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Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica , Receptores de Inositol 1,4,5-Trifosfato , Animales , Ratas , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/etiología , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Riñón , Minerales/metabolismo , Hormona ParatiroideaRESUMEN
IgA nephropathy (IgAN) is characterized by deposition of galactose-deficient IgA1 (Gd-IgA1) in glomerular mesangium associated with mucosal immune disorders. Since environmental pollution has been associated with the progression of chronic kidney disease in the general population, we specifically investigated the influence of exposure to fine particulate matter less than 2.5 µm in diameter (PM2.5) on IgAN progression. Patients with biopsy-proven primary IgAN were recruited from seven Chinese kidney centers. PM2.5 exposure from 1998 to 2016 was derived from satellite aerosol optical depth data and a total of 1,979 patients with IgAN, including 994 males were enrolled. The PM2.5 exposure levels for patients from different provinces varied but, in general, the PM2.5 exposure levels among patients from the north were higher than those among patients from the south. The severity of PM2.5 exposure in different regions was correlated with regional kidney failure burden. In addition, each 10 µg/m3 increase in annual average concentration of PM2.5 exposure before study entry (Hazard Ratio, 1.14; 95% confidence interval, 1.06-1.22) or time-varying PM2.5 exposure after study entry (1.10; 1.01-1.18) were associated with increased kidney failure risk after adjustment for age, gender, estimated glomerular filtration rate, urine protein, uric acid, hemoglobin, mean arterial pressure, Oxford classification, glucocorticoid and renin-angiotensin system blocker therapy. The associations were robust when the time period, risk factors of cardiovascular diseases or city size were further adjusted on the basis of the above model. Thus, our results suggest that PM2.5 is an independent risk factor for kidney failure in patients with IgAN, but these findings will require validation in more diverse populations and other geographic regions.
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Contaminación del Aire , Glomerulonefritis por IGA , Insuficiencia Renal , Masculino , Humanos , Glomerulonefritis por IGA/epidemiología , Material Particulado/efectos adversos , Inmunoglobulina A , Contaminación del Aire/efectos adversosRESUMEN
BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD) and HIV infection. The number of people living with HIV on hemodialysis (HD) is increasing. However, there is no data about anemia and related therapies in this kind of patients in China. We aim to assess the difference in hemoglobin (Hgb) and treatments like erythropoietin and iron between HIV-HD patients and HD patients in Chengdu, China. METHODS: This cross-sectional study was conducted with data collection from January 2020 to June 2020. Thirty-four HIV-infected HD patients and thirty-five non-HIV-infected HD patients were included. Age, gender, dialysis vintage, single-pool (sp) Kt/V, Hgb, the dose of erythropoietin, ferritin, use of iron preparations, and serum albumin were collected in all patients. Time since HIV diagnosis, counts of CD4 + T cells, HIV RNA, and antiretroviral therapy for HIV infection were collected in HIV-infected patients. T-test, Mann-Whitney U test, and chi-square statistics were applied in SPSS. RESULTS: The Hgb of HIV-HD and HD groups were 105.70 (95.93-112.08) g/L and 112.00 (93.00-126.00) g/L respectively (P = 0.064). There was a statistically significant higher erythropoietin dosage used in the HIV-HD population (222.55 ± 115.47 U/kg/week) compared to the HIV-negative HD group (161.86 ± 110.31 U/kg/week) (P = 0.029). 16/34 (47.06%) HIV-HD patients and 5/35 (14.29%) HD patients were treated with iron preparations (P = 0.003). The ferritin levels were 316.50 (117.38-589.75) ng/ml and 272.70 (205.00-434.00) ng/ml in HIV-HD and HD groups respectively. CONCLUSIONS: A higher erythropoietin dosage and a higher probability of iron preparations may be required to maintain Hgb in HIV-HD patients compared with HD patients.
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Anemia/tratamiento farmacológico , Eritropoyetina/uso terapéutico , Infecciones por VIH/complicaciones , Hierro/uso terapéutico , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Diálisis Renal , Adulto , Anemia/sangre , Anemia/etiología , China , Estudios Transversales , Eritropoyetina/administración & dosificación , Femenino , Ferritinas/sangre , Infecciones por VIH/sangre , Hemoglobinas/metabolismo , Humanos , Hierro/administración & dosificación , Fallo Renal Crónico/sangre , Masculino , Persona de Mediana Edad , Albúmina Sérica/metabolismoRESUMEN
Vascular calcification is prominent in patients with chronic kidney disease (CKD) and is a strong predictor of cardiovascular mortality in the CKD population. However, the mechanism underlying CKD-associated vascular calcification remains unclear. To identify potential therapeutic targets, a 5/6 nephrectomy rat model was established by feeding of a high-phosphorous diet as the CKD group and compared with sham group rats at 4 and 16 weeks. Sequencing analyses of the rat aorta revealed 643 upregulated and 1023 downregulated genes at 4 weeks, as well as 899 upregulated and 1185 downregulated genes at 16 weeks in the CKD group compared to the sham group. Bioinformatics analyses suggested that SOST (which encodes sclerostin) and Wnt signaling are involved in CKD-associated vascular calcification. Furthermore, protein-protein interactions analysis revealed interactions between SOST, WNT5A, and WNT5B, that involved runt-related transcription factor 2 (RUNX2) and transgelin (TAGLN). SOST was increased in CKD-associated vascular calcification following reduction of the Wnt signaling, including WNT5A and WNT5B, both in vivo and in vitro. TargetScan was used to predict the microRNAs (miRNAs) targeting WNT5A and WNT5B. The expression levels of miR-542-3p, miR-298-3p, miR-376b-5p, and miR-3568 were significantly reduced, whereas that of miR-742-3p was significantly increased in calcified rat aortic vascular smooth muscle cells (VSMCs). In CKD rat aortas, the expression of miR-542-3p, miR-298-3p, miR-376b-5p, miR-3568, miR-742-3p, and miR-22-5p were significantly reduced at both 4 and 16 weeks. Altogether, owing to several assessments, potentially diagnostic and prognostic biomarkers for improving common CKD diagnostic tools were identified in this study. Abbreviations: BUN: blood urea nitrogen; CKD: chronic kidney disease; CKD-MBD: chronic kidney disease-mineral bone disorder; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GO: the Gene Ontology; HE: hematoxylin-eosin; HRP: horseradish peroxidase; KEGG: Kyoto Encyclopedia of Genes and Genomes; MiRNAs: microRNAs; PAS: periodic acid-Schiff; RUNX2: runt-related transcription factor 2; SCr: serum creatinine; STRING: the Search Tool for the Retrieval of Interacting Genes/Proteins; TAGLN: transgelin; VSMC: vascular smooth muscle cell.
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MicroARNs , Insuficiencia Renal Crónica , Calcificación Vascular , Animales , Transdiferenciación Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Ratas , Insuficiencia Renal Crónica/metabolismo , Calcificación Vascular/genética , Calcificación Vascular/metabolismo , Vía de Señalización WntRESUMEN
Chronic kidney disease (CKD) has recently become a serious health and social concern. Vascular calcification, a common complication of CKD, is a risk factor that increases the incidence and mortality of cardiovascular events in patients with CKD. However, there are currently no effective therapeutic targets that can facilitate treatment with fewer side effects for vascular calcification in CKD. To identify potential therapeutic targets, we performed label-free quantification (LFQ) analyses of protein samples from rat aortic vascular smooth muscle cells (RASMCs) after high-phosphorus treatment by nano-UPLC-MS/MS. We determined that ubiquitin-specific protease 47 (USP47) may be associated with CKD vascular calcification by regulating the osteogenic transdifferentiation of the vascular smooth muscle cell (VSMC) phenotype, thus suggesting a novel and potentially effective therapeutic target for CKD vascular calcification. USP47 knockdown significantly reduced the expression of ß-transducin repeat-containing protein (BTRC), serine/threonine-protein kinase akt-1 (AKT1), Klotho, fibroblast growth factor (FGF23), and matrix Gla protein (MGP) in RASMCs after high-phosphorus treatment. Consistent with the results of protein-protein interaction (PPI) analyses, USP47 may be involved in regulating osteogenic transdifferentiation markers, such as runt-related transcription factor 2 (RUNX2), Klotho, FGF23, and MGP through the BTRC/AKT1 pathway upon CKD vascular calcification. These data indicate that USP47 may be associated with vascular calcification in CKD by regulating osteogenic differentiation of VSMCs. USP47 may regulate osteogenic transdifferentiation in VSMCs upon CKD vascular calcification through a process involving the BTRC/AKT1 pathway. This study identified a novel potential therapeutic target for the treatment of vascular calcification in CKD.
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Insuficiencia Renal Crónica , Proteasas Ubiquitina-Específicas , Calcificación Vascular , Animales , Transdiferenciación Celular/genética , Células Cultivadas , Femenino , Humanos , Masculino , Músculo Liso Vascular , Miocitos del Músculo Liso/metabolismo , Osteogénesis/genética , Fósforo/metabolismo , Ratas , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/metabolismo , Espectrometría de Masas en Tándem , Proteasas Ubiquitina-Específicas/metabolismo , Proteasas Ubiquitina-Específicas/farmacología , Calcificación Vascular/metabolismoRESUMEN
INTRODUCTION: Virtual home visits may improve chronic disease management. However, whether they are suitable for peritoneal dialysis (PD) patients has not yet been fully investigated. This study aimed to compare the agreement and acceptance of virtual home visits and in-person home visits in PD patients. METHODS: This was a paired, single center, noninferiority trial. Participants received a virtual home visit and an in-person home visit simultaneously. A home visit checklist was built for standardization visits. The content was divided into three parts: domestic habits (57 items), bag exchange procedures (56 items), and exit site care (53 items). Satisfaction questionnaires for both patients and nurses were designed to assess attitudes toward home visits and socioeconomic effects. RESULTS: A total of 30 PD patients were enrolled in a single center. The information collected from virtual home visits and in-person home visits was found to be highly consistent. The perfect agreement was found in 52/57, 49/56, and 44/53 items (Cohen's kappa 0.81-1.00), substantial agreement in 4/57, 7/56, and 8/53 items (Cohen's kappa 0.61-0.80). Patients reported almost identical satisfaction for virtual home visits and in-person home visits (Z = 0.39, p = 0.70). PD nurses reported similar feasibility and patient cooperation for the two visit types (Z = 0.99, p = 0.33; Z = 1.65, p = 0.10, respectively). In addition, virtual home visits were found to be more cost-effective than in-person home visits. CONCLUSIONS: Virtual home visits information collection was similar to in-person home visits in PD. There were no differences in participant satisfaction and feasibility between the two visit types.
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Visita Domiciliaria , Diálisis Peritoneal , Estudios de Factibilidad , Humanos , Cooperación del Paciente , Encuestas y CuestionariosRESUMEN
Immunoglobulin G (IgG) molecules modulate an immune response. However, site-specific N-glycosylation signatures of plasma IgG in patients with chronic kidney disease (CKD) remain unclear. This study aimed to propose a novel method to explore the N-glycosylation pattern of IgG and to compare it with reported methods. We separated human plasma IgG from 58 healthy controls (HC) and 111 patients with CKD. Purified IgG molecules were digested by trypsin. Tryptic peptides without enrichment of intact N-glycopeptides were analyzed using a combination of electron-transfer/higher-energy collisional dissociation (EThcD) and stepped collision energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (EThcD-sceHCD-MS/MS). This resulted in higher spectral quality, more informative fragment ions, higher Byonic score, and nearly twice the depth of intact N-glycopeptide identification than sceHCD or EThcD alone. Site-specific N-glycosylation mapping revealed that intact N-glycopeptides were differentially expressed in HC and CKD patients; thus, it can be a diagnostic tool. This study provides a method for the determination of glycosylation patterns in CKD and a framework for understanding the role of IgG in the pathophysiology of CKD. Data are available via ProteomeXchange with identifier PXD027174.
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Insuficiencia Renal Crónica , Espectrometría de Masas en Tándem , Glicopéptidos , Humanos , Inmunoglobulina G , Insuficiencia Renal Crónica/diagnóstico , Análisis de SistemasRESUMEN
BACKGROUND: Roxadustat has been shown effective in treating patients with anemia due to chronic kidney disease. However, its long-term effect on clinical outcomes and socioeconomic burden and safety remains unclear. METHODS/DESIGN: This is a multicenter, prospective, longitudinal observational cohort study assessing if Roxadustat improves prognosis in dialysis patients. Primary outcomes will be major adverse cardiovascular events (MACE), defined as composites of cardiovascular death, myocardial infarction, cerebral infarction, hospitalization because of heart failure; all-cause mortality, and annual economic costs in two years. The data will be collected via Research electronic data capture (REDCap) based database as well as software-based dialysis registry of Sichuan province. The primary outcomes for the ROAD study participants will be compared with those in the dialysis registry cohort. Data at baseline and study follow up will also be compared to assess the association between Roxadustat and long-term clinical outcomes. DISCUSSION: The main objective of this study is to the assess long-term association of Roxadustat on MACE, all-cause mortality, socio-economic burden, safety in dialysis patients, which will provide guidance for designing further large randomized controlled trials to investigate this clinic question. STUDY REGISTRATION: The study has been registered in Chinese Clinical Trials Registry (ROAD, ROxadustat in treating Anemia in Dialysis patients, registration number ChiCTR1900025765) and provincial observational cohort database (Renal disEAse observational CoHort database, REACH, ChiCTR1900024926), registered 07 September 2019, http://www.chictr.org.cn .
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Anemia/tratamiento farmacológico , Anemia/etiología , Glicina/análogos & derivados , Isoquinolinas/uso terapéutico , Estudios Multicéntricos como Asunto , Estudios Observacionales como Asunto , Diálisis Renal , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Proyectos de Investigación , Protocolos Clínicos , Estudios de Cohortes , Glicina/uso terapéutico , Humanos , Estudios ProspectivosRESUMEN
BACKGROUND: Macroscopic hematuria after wasp sting has been reported in Asia to occur before acute kidney injury (AKI), and is often used by clinicians as a sign indicating the need for intensive care and blood purification therapy. However, there is no study on the clinical characteristics and prognosis of this symptom. METHODS: The clinical data of 363 patients with wasp sting admitted to Suining Central Hospital from January 2016 to December 2018 were retrospectively analyzed. At admission, the poisoning severity score (PSS) was used as the criterion for severity classification. According to the presence of macroscopic hematuria, the patients were divided into macroscopic hematuria and non-macroscopic hematuria group. RESULTS: Of the 363 wasp sting patients, 219 were male and 144 were female, with a mean age of 55.9 ± 16.3 years. Fifty-one (14%) had macroscopic hematuria, 39 (10.7%) had AKI, 105 (28.9%) had rhabdomyolysis, 61 (16.8%) had hemolysis, 45 (12.4%) went on to received hemodialysis, and 14 (3.9%) died. The incidence of AKI in macroscopic hematuria group was 70.6%, and oliguric renal failure accounted for 72.2%. Patients with macroscopic hematuria had significantly higher PSS (2.2 ± 0.5 vs. 1.1 ± 0.3, p < .001). CONCLUSION: Macroscopic hematuria can be regarded as a surrogate marker of deteriorating clinical outcome following wasp stings. In wasp sting patients with symptoms of macroscopic hematuria or serum LDH higher than 463.5 u/L upon admission, the risk of AKI increases significantly, therefore hemodialysis should be considered. The PSS is helpful in early assessment of the severity of wasp sting patients.
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Lesión Renal Aguda/etiología , Hematuria/etiología , Mordeduras y Picaduras de Insectos/complicaciones , L-Lactato Deshidrogenasa/sangre , Venenos de Avispas/toxicidad , Lesión Renal Aguda/sangre , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/terapia , Adulto , Anciano , Animales , China/epidemiología , Femenino , Hematuria/epidemiología , Hematuria/terapia , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Diálisis Renal/estadística & datos numéricos , Estudios Retrospectivos , Rabdomiólisis/epidemiología , Índice de Severidad de la Enfermedad , AvispasRESUMEN
Defined differently from apoptosis, necrosis, and autophagy, ferroptosis has been implicated in acute kidney injury (AKI) such as ischemia-reperfusion injury induced AKI, folic acid caused AKI and cisplatin induced AKI. However, whether ferroptosis is involved in LPS induced AKI could be remaining unclear and there is still a lack of therapies associated with ferroptosis in LPS induced AKI without side effects. This study aimed to elucidate the role of isoliquiritigenin (ISL) in ferroptosis of LPS-induced AKI. We used LPS to induce renal tubular injury, followed by treatment with ISL both in vitro and in vivo. Human renal tubular HK2 cells were pretreated with 50 µM or 100 µM ISL for 5 h before stimulation with 2 µg/mL LPS. Mice were administered a single dose of either 50 mg/kg ISL orally or 5 mg/kg ferroptosis inhibitor ferrostatin-1 intraperitoneally before 10 mg/kg LPS injection. We found that LPS could induce mitochondria injury of renal tubular presented as the shape of mitochondria appeared smaller than normal with increased membrane density and are faction or destruction of mitochondrial crista through scanning electron microscope. Ferrostatin-1 significantly protected mice against renal dysfunction and renal tubular damage in LPS-induced AKI. ISL inhibited Fe2+ and lipid peroxidation accumulation in LPS-stimulated HK2 cells. It also increased the expression of GPX4 and xCT, reduced the expression of HMGB1 and NCOA4 then attenuated mitochondria injury in renal tubular following LPS stimulation. These results indicated the potential role of ISL against ferritinophagy-mediated ferroptosis in renal tubular following LPS stimulation.