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The maintenance of hematopoietic stem cell (HSC) functional integrity is essential for effective hematopoietic regeneration when suffering from injuries. Studies have shown that the innate immune pathways play crucial roles in the stress response of HSCs, whereas how to precisely modulate these pathways is not well characterized. Here, we identify the E3 ubiquitin ligase tripartite motif-containing 47 (Trim47) as a negative regulator of the mitochondrial antiviral-signaling protein (MAVS)-mediated innate immune pathway in HSCs. We find that Trim47 is predominantly enriched in HSCs, and its deficiency impairs the function and survival of HSCs after exposure to 5-flurouracil (5-FU) and irradiation (IR). Mechanistically, Trim47 impedes the excessive activation of the innate immune signaling and inflammatory response via K48-linked ubiquitination and degradation of MAVS. Collectively, our findings demonstrate a role of Trim47 in preventing stress-induced hematopoietic failure and thus provide a promising avenue for treatment of related diseases in the clinic.
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Proteínas Adaptadoras Transductoras de Señales , Células Madre Hematopoyéticas , Inmunidad Innata , Ratones Endogámicos C57BL , Transducción de Señal , Ubiquitina-Proteína Ligasas , Ubiquitinación , Animales , Células Madre Hematopoyéticas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Ratones , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ratones Noqueados , Humanos , Fluorouracilo/farmacología , Estrés Fisiológico , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Células HEK293RESUMEN
Background: This study investigates the link between genetic variants associated with kidney function and immunoglobulin A (IgA) nephropathy (IgAN) progression. Methods: We recruited 961 biopsy-proven IgAN patients and 651 non-IgAN end-stage renal disease (ESRD) patients from Ruijin Hospital. Clinical and renal pathological data were collected. The primary outcome was the time to ESRD. A healthy population was defined as estimated glomerular filtration rate >60 mL/min/1.73 m2 without albuminuria or hematuria. Fifteen single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of kidney function and genotyped by the SNaPshot. Immunohistochemistry in renal tissue and ELISA in urine samples were performed to explore the potential functions of genetic variations. Results: The rs77924615-G was independently associated with an increased risk for ESRD in IgAN patients after adjustments for clinical and pathologic indices, and treatment (adjusted hazard ratio 2.10; 95% confidence interval 1.14-3.88). No significant differences in ESRD-free survival time were found among different genotypes in non-IgAN ESRD patients (log-rank, P = .480). Moreover, rs77924615 exhibited allele-specific enhancer activity by dual-luciferase reporter assay. Accordingly, the urinary uromodulin-creatinine ratio (uUCR) was significantly higher in healthy individuals with rs77924615 AG or GG than in individuals with AA. Furthermore, uromodulin expression in tubular epithelial cells was higher in patients with rs77924615 AG or GG. Finally, we confirmed that an increased uUCR (P = .009) was associated with faster IgAN progression. Conclusion: The SNP rs77924615, which modulates the enhancer activity of the UMOD gene, is associated with renal function deterioration in IgAN patients by increasing uromodulin levels in both the renal tubular epithelium and urine.
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Background: Few studies have evaluated the treatment of immunoglobulin A nephropathy (IgAN) patients with nephrotic syndrome (NS) and mesangioproliferative glomerulonephritis (MPGN). The aim of this study was to compare the therapeutic effects of oral glucocorticoids (GCS) combined with intravenous cyclophosphamide (CTX) and oral GCS alone in the treatment of the MPGN-IgAN patients with NS. Methods: Biopsy-proven primary IgAN patients who were aged ≥14 years at diagnosis, had coexistent NS and MPGN and estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2, and were treated by oral GCS combined with intravenous CTX or oral GCS alone for 6-12 months were retrospectively included. The patients in the GCS + CTX (prednisone 0.6-0.8 mg/kg/day and intravenous CTX 0.6-1.0 g monthly) or GCS (prednisone 0.8-1 mg/kg/day) group were rather matched at a 1:1 ratio on key characteristics by propensity score matching. The primary outcome was defined as either complete remission or partial remission at Month 24. The secondary outcome was a composite renal endpoint defined as a 50% decline in eGFR, doubling of serum creatinine or progression to end-stage kidney disease. Results: Among the 146 IgAN patients who met the inclusion criteria, 42 patients were enrolled in the GCS + CTX group, and 42 patients were enrolled in the GCS group after propensity score matching. The clinical and histological parameters were similar between the two groups. Remission occurred more frequently in the GCS + CTX group at Month 6 (88.1% vs 52.4%, P < 0.001), Month 12 (88.1% vs 56.1%, P = 0.001) and Month 24 (85.0% vs 47.5%, P < 0.001) than in the GCS group. Moreover, subgroup analysis revealed that the higher response rate at Month 24 in the GCS + CTX group than in the GCS group was also present in different subgroups defined by sex, age, eGFR or Oxford MEST-C. Notably, we found that eGFR decreased at a lower rate in patients from the GCS + CTX group than in patients from the GCS group [eGFR slope: 0.05(-3.09, 3.67) vs -2.56 (-11.30, 0.86) mL/min/1.73 m2/year, P = 0.03]. Based on multivariate Cox regression analysis, GCS + CTX treatment was found to be independently associated with a decrease in risk for the composite endpoint after adjusted by the International Risk Prediction Score with race (hazard ratio = 0.17, 95% confidence interval 0.04-0.83, P = .03). There was no significant difference in adverse events (50.0% vs 42.9%, P = 0.51) or serious adverse events (7.1% vs 11.9%, P = .71) between the two groups. Conclusions: Oral GCS combined with intravenous CTX is superior to GCS alone in treating MPGN-IgAN patients combined with NS. As the retrospective design and small sample size, our findings need to be validated by a prospective study.
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PURPOSE: To examine the numbers and characteristics of children affected by asthma exacerbation in Chengdu, China, before and after the COVID-19 pandemic to inform efforts to manage childhood asthma in the post epidemic era. METHODS: Data were retrospectively collected from children admitted for asthma exacerbation to Chengdu Women and Children's Central Hospital between January 2017 and December 2022. Rates of hospitalization, ages of the affected children, comorbidities and infections, and relationships between hospitalization and seasonal or environmental factors were examined before and after the epidemic. RESULTS: Fewer children were hospitalized for asthma exacerbation, yet more hospitalized children had severe exacerbation after the epidemic than before. Rates of hospitalization varied considerably with time of year, and the timing of peak hospitalizations differed before and after the epidemic. Only before the epidemic, rates of hospitalization for asthma exacerbation were positively correlated with humidity. Infants made up a smaller proportion of hospitalized children after the epidemic than before, with preschool children accounting for most hospitalizations after the epidemic. The proportion of children hospitalized for asthma exacerbation who also had pneumonia was significantly smaller after the epidemic than before. Conversely, the proportion of children hospitalized for asthma exacerbation who also had allergic diseases was significantly greater after the epidemic than before. CONCLUSION: The epidemiology of asthma exacerbation in children changed after the epidemic. Future efforts to manage the condition in the paediatric population should focus on severe asthma exacerbation, prevention and management of allergic diseases, and the influence of meteorological and environmental factors.
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Asma , COVID-19 , Hipersensibilidad , Lactante , Preescolar , Humanos , Femenino , Niño , Estudios Retrospectivos , Pandemias , COVID-19/epidemiología , Asma/epidemiología , Hospitalización , Hipersensibilidad/epidemiología , China/epidemiologíaRESUMEN
Limited studies have investigated the microbial colonization of the airways and intestines in preterm neonates. We studied the composition of intestinal and airway bacterial colonies in several preterm twin pairs and singletons to explore the dominant bacteria, assess their variability, and predict their phenotypic and metabolic functions. In this descriptive study, we collected sputum and fetal stool specimens from 10 twin pairs (20 cases) and 20 singleton preterm neonates. These specimens were analyzed using 16S rRNA deep sequencing to study the alpha and beta diversities and community structures of airway and intestinal bacteria and predict their metabolic functions. Specimens from twins and singleton neonates had distinct aggregations of intestinal and airway bacteria but showed similarities and high microbial diversities during initial colonization. The top five phyla were Proteobacteria, Firmicutes, Actinobacteriota, Bacteroidota, and Cyanobacteria. The top ten genera were Streptococcus, Acinetobacter, Ralstonia, Staphylococcus, Comamonas, Enterococcus, Stenotrophomonas, Dechlorosoma, Sphingopyxis, and Rothia. Potentially pathogenic and highly stress-tolerant Gram-negative bacteria were predominant in the intestinal flora. A considerable proportion of colonies recovered from the airway and intestines of preterm neonates were functional bacteria. The richness of the intestinal and airway flora was not significantly different between twins and singletons, and the flora clustered together. Both intestinal and airway bacteria of twins and singletons were similar. The species involved in initial colonization were similar but different in proportions; therefore, changes in microbial structure and richness may not be attributed to these species.
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Objective: To examine the validity of the 5-component SARC-F questionnaire for screening sarcopenia among patients with chronic kidney disease (CKD). Methods: Eligible participants were enrolled from the Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from March 2019 to November 2019. Evaluations were performed using the self-administered SARC-F questionnaire. Sarcopenia was diagnosed by grip strength, the chair stand test and appendicular skeletal muscle mass. The severity of sarcopenia was evaluated by gait speed. We calculated the sensitivity and specificity of the SARC-F to evaluate construct validity. Moreover, receiver operating characteristic (ROC) curve analysis was performed to identify the cutoff value for nondialysis-dependent (NDD) CKD patients' and maintenance hemodialysis (MHD) patients' scores. Results: A total of 105 NDD-CKD patients and 125 MHD patients were included, and the prevalence of sarcopenia was 5.7 and 31.2%, respectively. Among them, there were 21 (16.8%) MHD patients with severe sarcopenia but no NDD-CKD patients with severe sarcopenia. The sensitivity and specificity of the SARC-F were 16.7 and 98.0% for NDD-CKD patients, and 48.7 and 89.5% for MHD patients, respectively. For NDD-CKD patients, the area under the receiver operating characteristic curve (AUROC) of the total SARC-F score was 0.978 (95% confidence interval (CI): 0.929-0.997, p < 0.001), and the cutoff value of 1 reached the highest Youden index of 0.950 and max ROC curve area of 0.974. For MHD patients, the AUROC of the total SARC-F score was 0.730 (95% CI: 0.644-0.806, p < 0.001), and the cutoff value of 4 reached the highest Youden index of 0.383 and max ROC curve area of 0.691. Conclusion: CKD patients, especially MHD patients, were at high risk of suffering sarcopenia. The SARC-F had low-to-moderate sensitivity but high specificity for screening sarcopenia among patients with CKD. The best cutoff values of the SARC-F score were different for screening sarcopenia among NDD-CKD and MHD patients.
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Background: Differences in bronchial microbiota composition have been found to be associated with asthma; however, it is still unclear whether these findings can be applied to recurrent wheezing in infants especially with aeroallergen sensitization. Objectives: To determine the pathogenesis of atopic wheezing in infants and to identify diagnostic biomarkers, we analyzed the bronchial bacterial microbiota of infants with recurrent wheezing and with or without atopic diseases using a systems biology approach. Methods: Bacterial communities in bronchoalveolar lavage samples from 15 atopic wheezing infants, 15 non-atopic wheezing infants, and 18 foreign body aspiration control infants were characterized using 16S rRNA gene sequencing. The bacterial composition and community-level functions inferred from between-group differences from sequence profiles were analyzed. Results: Both α- and ß-diversity differed significantly between the groups. Compared to non-atopic wheezing infants, atopic wheezing infants showed a significantly higher abundance in two phyla (Deinococcota and unidentified bacteria) and one genus (Haemophilus) and a significantly lower abundance in one phylum (Actinobacteria). The random forest predictive model of 10 genera based on OTU-based features suggested that airway microbiota has diagnostic value for distinguishing atopic wheezing infants from non-atopic wheezing infants. PICRUSt2 based on KEGG hierarchy (level 3) revealed that atopic wheezing-associated differences in predicted bacterial functions included cytoskeleton proteins, glutamatergic synapses, and porphyrin and chlorophyll metabolism pathways. Conclusion: The differential candidate biomarkers identified by microbiome analysis in our work may have reference value for the diagnosis of wheezing in infants with atopy. To confirm that, airway microbiome combined with metabolomics analysis should be further investigated in the future.
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Bronquios , Ruidos Respiratorios , Humanos , Lactante , Proyectos Piloto , ARN Ribosómico 16S , BacteriasRESUMEN
Numerous studies have discovered that chronic stress induces metabolic disorders by affecting iron and zinc metabolism, but the relationship between chronic stress and copper metabolism remains unclear. Here, we explore the influence of chronic corticosterone (CORT) exposure on copper metabolism and its regulatory mechanism in mice. Mice were treated with 100 µg/mL CORT in drinking water for a 4-week trial. We found that CORT treatment resulted in a significant decrease in plasma copper level, plasma ceruloplasmin activity, plasma and liver Cu/Zn-SOD activity, hepatic copper content, and liver metallothionein content in mice. CORT treatment led to the reduction in duodenal expression of copper transporter 1 (CTR1), duodenal cytochrome b (DCYTB), and ATPase copper-transporting alpha (ATP7A) at the mRNA and protein level in mice. CORT treatment activated nuclear glucocorticoid receptor (GR) and down-regulated CRT1 expression in Caco-2 cells, whereas these phenotypes were reversible by an antagonist of GR, RU486. Chromatin immunoprecipitation analysis revealed that GR bound to the Ctr1 promoter in Caco-2 cells. Transient transfection assays in Caco-2 cells demonstrated that the Ctr1 promoter was responsive to the CORT-activated glucocorticoid receptor, whereas mutation/deletion of the glucocorticoid receptor element (GRE) markedly impaired activation of the Ctr1 promoter. In addition, CORT-induced downregulation of Ctr1 promoter activity was markedly attenuated in Caco-2 cells when RU486 was added. These findings present a novel molecular target for CORT that down-regulates intestinal CTR1 expression via GR-mediated trans-repression in mice.
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To explore the changes in iron metabolism and mitochondrial function exposed to chronic psychological stress, seventy-five male mice aged 5 ~ 6 weeks were randomly sorted into 2 groups: control group and chronic psychological stress group. Mice were conducted by communication box to induce psychological stress for 21 consecutive days. The results showed that chronic psychological stress led to a significant reduction in average daily gain (P < 0.01) and the final weight (P < 0.05). Chronic psychological stress greatly increased plasma and duodenal iron level (P < 0.05), whereas markedly decreased hepatic iron content in mice (P < 0.05). Increasing expression of duodenal DCYTB and FPN (P < 0.05) was observed in mice exposed to chronic psychological stress. Moreover, chronic psychological stress greatly enhanced hepatic TFR1, FTL, and FPN protein expression (P < 0.05) in mice. Additionally, chronic psychological stress enhanced the levels of hepatic NADH, NAD + , ATP, mtDNA content, mtDNA-encoded genes, and the activity of mitochondrial complex I and II (P < 0.05). Taken together, chronic psychological stress impairs growth, disrupts iron metabolism, and enhances hepatic mitochondrial function in mice. These results will provide new insights for understanding the mechanisms of iron metabolism and mitochondrial function during chronic psychological stress.
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Hierro , Mitocondrias , Ratones , Masculino , Animales , Hierro/metabolismo , Mitocondrias/metabolismo , Hígado/metabolismo , Receptores de Transferrina/metabolismo , ADN Mitocondrial/metabolismoRESUMEN
OBJECTIVES: This study aimed to explore clinical features of early infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and to identify the association between the infection profile of patients with AAV during the first 3 months and 1-year survival. METHODS: A total of 415 newly diagnosed patients with AAV in the Department of Nephrology at Shanghai Ruijin Hospital from 2000 to 2018 were included. Four Cox regression models were used to analyse the association based on demographics, comorbidities, laboratory baseline index and therapy parameter. Infection screening was carried out monthly during the first 3 months after diagnosis. RESULTS: In all, 377 episodes of infection were identified among 220 patients during the first 3 months. The overall survival after 1 year was 73.0%. Respiratory infection (210 episodes/164 persons) accounted for more than half of infections. Infection was independently associated with 1-year mortality (adjusted HR 2.32, 95% CI 1.27 to 4.23, p=0.006) after adjustment. Respiratory infection (adjusted HR 4.36, 95% CI 2.86 to 8.06, p<0.001), Gram-negative bacterial infection (adjusted HR 1.71, 95% CI 1.01 to 2.91, p=0.047) and fungal infection (adjusted HR 1.77, 95% CI 1.07 to 2.94, p=0.026) was identified as a risk factor for 1-year mortality. Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis (adjusted HR 0.55, 95% CI 0.31 to 0.97, p=0.040) was protective for 1-year mortality. CONCLUSIONS: Infections, particularly respiratory infections, are a common and important class of complication in patients with AAV and are associated with early mortality. TMP-SMX prophylaxis might be necessary to improve short-term outcome. More consideration of infectious risk and regular infection screening should be given.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Anticuerpos Anticitoplasma de Neutrófilos , Humanos , Anticuerpos Anticitoplasma de Neutrófilos/uso terapéutico , Estudios Retrospectivos , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , China , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológicoRESUMEN
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
In secondary hyperparathyroidism (SHPT) disease, preoperatively localizing hyperplastic parathyroid glands is crucial in the surgical procedure. These glands can be detected via the dual-modality imaging technique single-photon emission computed tomography/computed tomography (SPECT/CT) since it has high sensitivity and provides an accurate location. However, due to possible low-uptake glands in SPECT images, manually labeling glands is challenging, not to mention automatic label methods. In this work, we present a deep learning method with a novel fusion network to detect hyperplastic parathyroid glands in SPECT/CT images. Our proposed fusion network follows the convolutional neural network (CNN) with a three-pathway architecture that extracts modality-specific feature maps. The fusion network, composed of the channel attention module, the feature selection module, and the modality-specific spatial attention module, is designed to integrate complementary anatomical and functional information, especially for low-uptake glands. Experiments with patient data show that our fusion method improves performance in discerning low-uptake glands compared with current fusion strategies, achieving an average sensitivity of 0.822. Our results prove the effectiveness of the three-pathway architecture with our proposed fusion network for solving the glands detection task. To our knowledge, this is the first study to detect abnormal parathyroid glands in SHPT disease using SPECT/CT images, which promotes the application of preoperative glands localization.
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We aimed to validate three IgAN risk models proposed by an international collaborative study and another CKD risk model generated by an extended CKD cohort with our multicenter Chinese IgAN cohort. Biopsy-proven IgAN patients with an eGFR ≥15 ml/min/1.73 m2 at baseline and a minimum follow-up of 6 months were enrolled. The primary outcomes were a composite outcome (50% decline in eGFR or ESRD) and ESRD. The performance of those models was assessed using discrimination, calibration, and reclassification. A total of 2,300 eligible cases were enrolled. Of them, 288 (12.5%) patients reached composite outcome and 214 (9.3%) patients reached ESRD during a median follow-up period of 30 months. Using the composite outcome for analysis, the Clinical, Limited, Full, and CKD models had relatively good performance with similar C statistics (0.81, 0.81, 0.82, and 0.82, respectively). While using ESRD as the end point, the four prediction models had better performance (all C statistics > 0.9). Furthermore, subgroup analysis showed that the models containing clinical and pathological variables (Full model and Limited model) had better discriminatory abilities than the models including only clinical indicators (Clinical model and CKD model) in low-risk patients characterized by higher baseline eGFR (≥60 ml/min/1.73 m2). In conclusion, we validated recently reported IgAN and CKD risk models in our Chinese IgAN cohort. Compared to pure clinical models, adding pathological variables will increase performance in predicting ESRD in low-risk IgAN patients with baseline eGFR ≥60 ml/min/1.73 m2.
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Glomerulonefritis por IGA/epidemiología , Adulto , Estudios de Cohortes , Creatinina/sangre , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Mesangio Glomerular/química , Mesangio Glomerular/patología , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/patología , Glucocorticoides/uso terapéutico , Hospitales de Enseñanza , Humanos , Inmunoglobulina A/análisis , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/etiología , Masculino , Microscopía Fluorescente , Persona de Mediana Edad , Modelos Teóricos , Estudios Multicéntricos como Asunto/estadística & datos numéricos , Pronóstico , Proteinuria/etiología , Curva ROC , Sistema Renina-Angiotensina/efectos de los fármacos , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. METHODS: In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. RESULTS: In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin time (PT) on admission. For every 0.1 mmol/L decreases in serum phosphorus level, patients had a 1.34-fold (95% CI 1.14-1.58) increased risk of AKI. Patients with hypophosphatemia were likely to be older and with lower lymphocyte count, lower serum albumin level, lower uric acid, higher LDH, and higher CRP. Furthermore, serum phosphorus level was positively correlated with phosphate tubular maximum per volume of filtrate (TmP/GFR) (Pearson r = 0.66, p < .001) in subgroup analysis, indicating renal phosphate loss via proximal renal tubular dysfunction. CONCLUSION: The AKI incidence was very low in non-ICU patients as compared to ICU patients. Hypophosphatemia is an independent risk factor for AKI in patients hospitalized for COVID-19 infection.
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Lesión Renal Aguda/etiología , COVID-19/complicaciones , Hipofosfatemia/complicaciones , Neumonía Viral/complicaciones , Lesión Renal Aguda/epidemiología , COVID-19/epidemiología , China/epidemiología , Femenino , Hospitalización , Humanos , Hipofosfatemia/epidemiología , Incidencia , Unidades de Cuidados Intensivos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Neumonía Viral/epidemiología , Neumonía Viral/virología , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
OBJECTIVE: Hyperuricaemia is common in Bai individuals; however, its prevalence remains unclear. This work aimed to investigate high-altitude hyperuricaemia prevalence and risk factors in Bai individuals. METHODS: All eligible participants of Bai ethnicity (aged ≥18 years and undergoing routine medical examination at the People's Hospital of Jianchuan County between January and December 2019) were consecutively enrolled. Demographic and laboratory data were collected to investigate hyperuricaemia prevalence and associated risk factors. RESULTS: A total of 1393 participants were assessed, comprising 345 (24.8%) with hyperuricaemia showing a male predominance (287/865 [33.2%] males versus 58/528 [11.0%] females). Hyperuricaemia prevalence was significantly higher in participants aged ≥50 years (100/332 [30.1%]) versus those aged 30-40 years (59/308 [19.2%]), and in overweight/obese individuals compared with those showing an underweight or normal body mass index (BMI; 267/885 [30.2%] versus 78/508 [15.4%]). Finally, haemoglobin concentrations and serum uric acid levels were positively correlated. CONCLUSION: Besides traditional risk factors, including age, sex and BMI, polycythaemia due to prolonged exposure to high altitude may also cause hyperuricaemia in Bai individuals residing in Yunnan Province.
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Hiperuricemia , Adolescente , Adulto , Altitud , China/epidemiología , Estudios Transversales , Femenino , Humanos , Hiperuricemia/epidemiología , Masculino , Prevalencia , Factores de Riesgo , Ácido ÚricoRESUMEN
INTRODUCTION: Acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients is associated with poor prognosis. Early prediction and intervention of AKI are vital for improving clinical outcome of COVID-19 patients. As lack of tools for early AKI detection in COVID-19 patients, this study aimed to validate the USCD-Mayo risk score in predicting hospital-acquired AKI in an extended multi-center COVID-19 cohort. METHODS: Five hundred seventy-two COVID-19 patients from Wuhan Tongji Hospital Guanggu Branch, Wuhan Leishenshan Hospital, and Wuhan No. Ninth Hospital was enrolled for this study. Patients who developed AKI or reached an outcome of recovery or death during the study period were included. Predictors were evaluated according to data extracted from medical records. RESULTS: Of all patients, a total of 44 (8%) developed AKI. The UCSD-Mayo risk score achieved excellent discrimination in predicting AKI with the C-statistic of 0.88 (95%CI: 0.84-0.91). Next, we determined the UCSD-Mayo risk score had good overall performance (Nagelkerke R2 = 0.32) and calibration in our cohort. Further analysis showed that the UCSD-Mayo risk score performed well in subgroups defined by gender, age, and several chronic comorbidities. However, the discrimination of the UCSD-Mayo risk score in ICU patients and patients with mechanical ventilation was not good which might be resulted from different risk factors of these patients. CONCLUSIONS: We validated the performance of UCSD-Mayo risk score in predicting hospital-acquired AKI in COVID-19 patients was excellent except for patients from ICU or patients with mechanical ventilation.
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Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , COVID-19/complicaciones , Índice de Severidad de la Enfermedad , Lesión Renal Aguda/mortalidad , Adulto , Anciano , COVID-19/mortalidad , China/epidemiología , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
INTRODUCTION: Familial IgA nephropathy (IgAN) has been widely reported. However, its clinicohistologic characteristics and long-term prognosis are not clear. METHODS: A total of 348 familial IgAN cases from 167 independent families were recruited and their clinicohistologic characteristics as well as lifetime risk of end-stage renal disease (ESRD) were compared to 1116 sporadic IgAN patients from the same geographic region. RESULTS: Of all familial IgAN patients, 60 (17%) came from 32 single-generation (SG; all affected individuals are siblings) families, whereas 286 (82%) came from 134 multiple-generation (MG; affected individuals were present in at least 2 consecutive generations) families. The lifetime ESRD risk was significantly higher in familial patients than sporadic ones after adjusting by gender (hazard ratio [HR]=1.40, 95% confidence interval [CI]: 1.12-1.74, P = 0.004), with 5 years younger in median ESRD age (60 years vs. 65 years in familial and sporadic cases separately). Interestingly, among familial patients, we found cases from SG families (vs. MG families: HR = 2.62, 95% CI: 1.59-4.31, P < 0.001) or with early onset (onset age <30 years) (vs. late onset: HR = 4.79, 95% CI: 3.16-7.26, P < 0.001) had higher lifetime ESRD risk. Furthermore, among sporadic patients, men had lower estimated glomerular filtration rate (eGFR), higher urine protein, higher Oxford T score, and higher risk for life span ESRD compared with women (male vs. female, 25% vs. 17%, P = 0.003) whereas these gender differences were not seen in familial patients. CONCLUSION: Familial IgAN cases had poorer renal outcomes and less gender differences compared with sporadic cases. These findings provide evidence that familial disease represent a distinct subtype of more progressive IgAN. Early diagnosis could improve the prognosis of cases with familial IgAN.
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BACKGROUND: There is considerable state-level variation in the incidence of dialysis-requiring acute kidney injury (AKI-D). However, little is known about reasons for this geographic variation. METHODS: National cross-sectional state-level ecological study based on State Inpatient Databases (SID) and the Behavioral Risk Factor Surveillance System (BRFSS) in 2011. We analyzed 18 states and six chronic health conditions (diabetes mellitus [diabetes], hypertension, chronic kidney disease [CKD], arteriosclerotic heart disease [ASHD], cancer (excluding skin cancer), and chronic obstructive pulmonary disease [COPD]). Associations between each of the chronic health conditions and AKI-D incidence was assessed using Pearson correlation and multiple regression adjusting for mean age, the proportion of males, and the proportion of non-Hispanic whites in each state. RESULTS: The state-level AKI-D incidence ranged from 190 to 1139 per million population. State-level differences in rates of hospitalization with chronic health conditions (mostly < 3-fold difference in range) were larger than the state-level differences in prevalence for each chronic health condition (mostly < 2.5-fold difference in range). A significant correlation was shown between AKI-D incidence and prevalence of diabetes, ASHD, and COPD, as well as between AKI-D incidence and rate of hospitalization with hypertension. In regression models, after adjusting for age, sex, and race, AKI-D incidence was associated with prevalence of and rates of hospitalization with five chronic health conditions--diabetes, hypertension, CKD, ASHD and COPD--and rates of hospitalization with cancer. CONCLUSIONS: Results from this ecological analysis suggest that state-level variation in AKI-D incidence may be influenced by state-level variations in prevalence of and rates of hospitalization with several chronic health conditions. For most of the explored chronic conditions, AKI-D correlated stronger with rates of hospitalizations with the health conditions rather than with their prevalences, suggesting that better disease management strategies that prevent hospitalizations may translate into lower incidence of AKI-D.
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Lesión Renal Aguda/epidemiología , Diálisis Renal , Lesión Renal Aguda/terapia , Negro o Afroamericano , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Geografía , Hispánicos o Latinos , Hospitalización , Humanos , Incidencia , Modelos Lineales , Masculino , Persona de Mediana Edad , Prevalencia , Índice de Severidad de la Enfermedad , Estados Unidos , Población BlancaRESUMEN
Background: Both soluble suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are promising biomarkers associated with the adverse clinical outcomes of dialysis patients. Our research aims at exploring and comparing the roles of sST2 and NT-proBNP in predicting the short-term and long-term mortality of maintenance hemodialysis (MHD) patients.Methods: A prospective cohort study was performed. Patients undergoing hemodialysis in July 2014 were enrolled from the Blood Purification Center of Ruijin Hospital. MHD patients were followed up for 3 years. The primary outcome was all-cause mortality at the 1-year and 3-year follow-up, while the secondary outcome was cardiovascular mortality. Serum sST2 level was detected by quantified ELISA kits. Clinical data were analyzed by SPSS 23.0 version.Results: 205 patients were recruited. The median sST2 level was 15.99 (11.60, 20.49) ng/ml. After 3 years of follow-up, both all-cause and cardiovascular mortality in 1 year and all-cause and cardiovascular mortality in 3 years increased significantly with serum sST2. For short-term mortality, no significant difference was observed in patients with increasing NT-proBNP levels. Cox regression analysis indicated that only sST2 was independent in predicting the risk of short-term outcomes. For long-term mortality, both sST2 and NT-proBNP were independent risk factors, while a higher hazard ratio was observed for NT-proBNP.Conclusions: Serum sST2 is a novel biomarker associated with adverse clinical outcomes in MHD patients. It was significant for both all-cause and cardiovascular mortality in MHD patients and may provide better prognostic value in short-term prognosis than the classic biomarker NT-proBNP.
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Enfermedades Cardiovasculares/mortalidad , Proteína 1 Similar al Receptor de Interleucina-1/sangre , Diálisis Renal , Anciano , Biomarcadores/sangre , Causas de Muerte , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
INTRODUCTION: Heterotopic vascular calcification is a common complication of maintenance hemodialysis (MHD) patients. Galectin 3 (Gal-3) has been reported to be associated with cardiovascular calcification. The current study aims to explore the potential predictive value of serum Gal-3 for severe abdominal aortic calcification (AAC) and AAC progression in MHD patients. METHODS: A prospective cohort who underwent hemodialysis during July 2014 at the Blood Purification Center of Ruijin Hospital were followed up for 3 years. Two AAC assessments were performed: one at baseline and one after the 3-year follow-up period. Serum Gal-3 was detected with quantitative ELISA kits. SPSS 23.0 and MedCalc 11.4.2.0 were used to analyze the data. FINDINGS: One hundred and fifty-two patients were recruited. Approximately 59.9% were male, the median age was 60 (50-67) years. Logistic regression analysis indicated that serum Gal-3 was an independent risk factor for both follow-up severe AAC and AAC progression. Receiver operating characteristic (ROC) curve analysis revealed significant prognostic value of serum Gal-3 for predicting severe AAC and AAC progression within 3 years. DISCUSSION: We found serum Gal-3 is correlated to vascular calcification in ESRD patients. Gal-3 may be a potential biomarker of vascular calcification for MHD patients.