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BACKGROUND: Cardiac surgery-associated acute kidney injury (AKI) is one of the common complications of cardiac surgery. Preoperative angiography helps assess heart disease but may increase the risk of AKI. Although more and more patients with preoperative renal dysfunction can undergo cardiac surgery with the advances in surgical techniques, there is little research on the effect of angiography on postoperative AKI in these patients. This study investigates whether angiography increases the risk of AKI after cardiac surgery in patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m2). METHODS: Patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m2) who underwent angiography and cardiac surgery successively from January 2015 to December 2020 were retrospectively enrolled in this study. The primary outcome was postoperative AKI, defined as the Kidney Disease: Improving Global Outcomes Definition and Staging (KDIGO) criteria. Univariate analysis and multivariate regression were performed to identify the association between angiography timing and AKI. RESULTS: A total of 888 consecutive eligible patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m2) were enrolled in this study. The incidence of AKI was 48.31%. Male (OR = 1.903), the interval between angiography and surgery (0-2d OR = 2.161; 3-6d OR = 3.291), cross-clamp duration (OR = 1.009), were identified as predictors for AKI. The interval between angiography and surgery was also associated with AKI in the patients with 15 ≤ eGFR < 30ml/min/1.73m2 (0-2d OR = 4.826; 3-6d OR = 5.252), 30 ≤ eGFR < 45 ml/min/1.73m2 (0-2d OR = 2.952; 3-6d OR = 3.677), but not associated with AKI in patients with 45 ≤ eGFR < 60 ml/min/1.73m2. CONCLUSIONS: In patients with preoperative renal dysfunction, the interval between angiography and cardiac surgery (0-2d and 3-6d) was associated with AKI. For patients with poorer preoperative renal function, the interval between angiography and cardiac surgery is of great concern.
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Lesión Renal Aguda , Procedimientos Quirúrgicos Cardíacos , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Lesión Renal Aguda/diagnóstico por imagen , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , AngiografíaRESUMEN
BACKGROUND: Fluid overload is related to the development and prognosis of cardiac surgery-associated acute kidney injury (CSA-AKI). The study is to investigate the influence of serum creatinine (SCr) corrected by fluid balance on the prognosis of patients with cardiac surgery. METHODS: A retrospective study was conducted in 1334 patients who underwent elective cardiac surgery from January 1 to December 31, 2015. Kidney Disease: Improving Global Outcomes (KDIGO) criteria for AKI were applied to identify CSA-AKI. SCr was measured every 24 h during ICU period and was accordingly adjusted for cumulative fluid balance. Changes in SCr, defined as ∆Crea, were determined by difference between before and after adjustment for cumulative fluid balance. All patients were then divided into three groups: underestimation group (∆Crea ≥ P75), normal group (P25 < ∆Crea < P75) and overestimation group (∆Crea ≤ P25). RESULTS: The incidence of AKI increased from 29.5% to 31.8% after adjustment for fluid balance. Patients in underestimation group showed prolonged length of ICU stay compared with normal group and overestimation group (3.2 [1.0-4.0] vs 2.1 [1.0-3.0] d, P < 0.001; 3.2 [1.0-4.0] vs 2.3 [1.0-3.0] d, P < 0.001). Length of hospital stay and mechanical ventilation dependent days in underestimation group were significantly longer than normal group (P < 0.001). Multivariate analysis showed age, baseline SCr and left ventricular ejection fraction were independently associated with underestimation of creatinine. CONCLUSIONS: Cumulative fluid balance after cardiac surgery disturbs accurate measurement of serum creatinine. Patients with underestimation of SCr were associated with poor prognosis.
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Lesión Renal Aguda/diagnóstico , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Creatinina/sangre , Hemodilución/efectos adversos , Riñón/fisiopatología , Equilibrio Hidroelectrolítico , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Lesión Renal Aguda/fisiopatología , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Delayed diagnosis of acute kidney injury (AKI) is common because the changes in renal function markers often lag injury. We aimed to find optimal non-invasive hemodynamic variables for the prediction of postoperative AKI and AKI renal replacement therapy (RRT). METHODS: The data were collected from 1,180 patients who underwent cardiac surgery in our hospital between March 2015 and Feb 2016. Postoperative central venous pressure (CVP), mean arterial pressure (MAP), heart rate, PaO2, and PaCO2 on ICU admission and daily fluid input and output (calculated as 24 h PFO) were monitored and compared between AKI vs. non-AKI and RRT vs non-RRT cases. RESULTS: The AKI and AKI-RRT incidences were 36.7% (n = 433) and 1.2% (n = 14). Low cardiac output syndromes (LCOSs) occurred significantly more in AKI and RRT than in non-AKI or non-RRT groups (13.2% vs. 3.9%, P < 0.01; 42.9% vs. 7.1%, P < 0.01). CVP on ICU admission was significantly higher in AKI and RRT than in non-AKI and non-RRT groups (11.5 vs. 9.0 mmHg, P < 0.01; 13.3 vs. 9.9 mmHg, P < 0.01). 24 h PFO in AKI and RRT cases were significantly higher than in non-AKI or non-RRT patients (1.6% vs. 0.9%, P < 0.01; 3.9% vs. 0.8%, P < 0.01). The areas under the ROC curves to predict postoperative AKI by CVP on ICU admission (> 11 mmHg) + LCOS + 24 h PFO (> 5%) and to predict AKI-RRT by CVP on ICU admission (> 13 mmHg) + LCOS + 24 h PFO (> 5%) were 0.763 and 0.886, respectively. CONCLUSION: The volume-associated hemodynamic variables, including CVP on ICU admission, LCOS, and 24 h PFO after surgery could predict postoperative AKI and AKI-RRT.
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Lesión Renal Aguda/etiología , Lesión Renal Aguda/fisiopatología , Gasto Cardíaco Bajo/fisiopatología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Hemodinámica , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/terapia , Adulto , Anciano , Área Bajo la Curva , Presión Arterial , Líquidos Corporales , Dióxido de Carbono/sangre , Gasto Cardíaco Bajo/complicaciones , Presión Venosa Central , Femenino , Frecuencia Cardíaca , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Presión Parcial , Admisión del Paciente , Valor Predictivo de las Pruebas , Curva ROC , Terapia de Reemplazo Renal , Factores de RiesgoRESUMEN
BACKGROUND: Patients who were diagnosed with hematologic malignancies (HM) had a higher risk of acute kidney injury (AKI). This study applies the Bayesian networks (BNs) to investigate the interrelationships between AKI and its risk factors among HM patients, and to evaluate the predictive and inferential ability of BNs model in different clinical settings. METHODS: During 2014 and 2015, a total of 2501 inpatients with HM were recruited in this retrospective study conducted in a tertiary hospital, Shanghai of China. Patients' demographics, medical history, clinical and laboratory records on admission were extracted from the electronic medical records. Candidate predictors of AKI were screened in the group-LASSO (gLASSO) regression, and then they were incorporated into BNs analysis for further interrelationship modeling and disease prediction. RESULTS: Of 2395 eligible patients with HM, 370 episodes were diagnosed with AKI (15.4%). Patients with multiple myeloma (24.1%) and leukemia (23.9%) had higher incidences of AKI, followed by lymphoma (13.4%). Screened by the gLASSO regression, variables as age, gender, diabetes, HM category, anti-tumor treatment, hemoglobin, serum creatinine (SCr), the estimated glomerular filtration rate (eGFR), serum uric acid, serum sodium and potassium level were found with significant associations with the occurrence of AKI. Through BNs analysis, age, hemoglobin, eGFR, serum sodium and potassium had directed connections with AKI. HM category and anti-tumor treatment were indirectly linked to AKI via hemoglobin and eGFR, and diabetes was connected with AKI by affecting eGFR level. BNs inferences concluded that when poor eGFR, anemia and hyponatremia occurred simultaneously, the patients' probability of AKI was up to 78.5%. The area under the receiver operating characteristic curve (AUC) of BNs model was 0.835, higher than that in the logistic score model (0.763). It also showed a robust performance in 10-fold cross-validation (AUC: 0.812). CONCLUSION: Bayesian networks can provide a novel perspective to reveal the intrinsic connections between AKI and its risk factors in HM patients. The BNs predictive model could help us to calculate the probability of AKI at the individual level, and follow the tide of e-alert and big-data realize the early detection of AKI.
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Lesión Renal Aguda/epidemiología , Leucemia/epidemiología , Linfoma/epidemiología , Modelos Estadísticos , Mieloma Múltiple/epidemiología , Adulto , Factores de Edad , Anciano , Anemia/epidemiología , Teorema de Bayes , China/epidemiología , Femenino , Tasa de Filtración Glomerular , Hemoglobinas/metabolismo , Hospitalización , Humanos , Hiponatremia/epidemiología , Masculino , Persona de Mediana Edad , Potasio/sangre , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Sodio/sangreRESUMEN
OBJECTIVE: Spot urine sodium and associated estimating equations provide a suitable alternative assessment of 24-hour sodium excretion in many large-scale studies, but not in chronic kidney disease (CKD) patients with decreased renal function. Herein, we aimed to develop a novel predictive equation. DESIGN AND METHODS: We retrospectively enrolled all CKD patients at Stage 1-4 who received spot and 24-hour urinary analysis in our single center from January 1, 2014 to December 31, 2017. Multiple linear regression analysis generated a predictive equation for estimating 24-hour sodium excretion from spot urine samples in the derivation cohort admitted from 2014 to 2015, and then we assessed this predictive equation in a validation cohort admitted from 2016 to 2017. RESULTS: All 5,235 patients were finally analyzed and divided into derivation (n = 2,460) and validation (n = 2,775) cohort according to the admission date. We generated a predictive equation and defined it as "CKDSALT" equation because it was used for the estimation of salt intake in CKD patients. When we measured sodium excretion as the gold standard, we compared this novel validation with other 3 equations: Kawasaki, INTERSALT, and Tanaka. The Bland-Altman plots indicated that the CKDSALT equation showed the lowest bias with limits of agreement (bias = -1.25 mmol, 95% confidence interval -121.3 to 123.8), and the best performance in any subgroup analysis: male and female, old and young, different levels of body mass index, various levels of estimated glomerular filtration rate, and 24-hour urine volume. The CKDSALT equation also had the highest Pearson (0.745) and intraclass correlation coefficient (0.853, 95% confidence interval 0.841-0.863) in all validation cohort and the above subgroups. CONCLUSION: Spot urine method by CKDSALT equation may be promising for estimating 24-hour urinary sodium excretion in CKD patients with normal renal function and patients with decreased estimated glomerular filtration rate.
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Insuficiencia Renal Crónica/orina , Sodio/orina , Adulto , Anciano , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Urinálisis/métodosRESUMEN
Background: This study aims to delineate the incidence of electrolyte and acid-base disorders (EAD) in cancer patients, to figure out the risk factors of EAD, then to assess the impact of EAD on patients' in-hospital clinical outcomes.Methods: Patients with the diagnosis of malignancies hospitalized during 1 October 2014 and 30 September 2015 were recruited in Zhongshan Hospital, Fudan University in Shanghai of China. Demographic characteristics, comorbidities, and clinical data, including survival, length of stay and hospital cost, were extracted from the electronic medical record system. Electrolyte and acid-base data were acquired from the hospital laboratory database.Results: Of 25,881 cancer patients with electrolyte data, 15,000 (58.0%) cases had at least one electrolyte and acid-base abnormity. Hypocalcemia (27.8%) was the most common electrolyte disorder, followed by hypophosphatemia (26.7%), hypochloremia (24.5%) and hyponatremia (22.5%). The incidence of simple metabolic acidosis (MAC) and metabolic alkalosis (MAL) was 12.8% and 22.1% respectively. Patients with mixed metabolic acid-base disorders (MAC + MAL) accounted for 30.2%. Lower BMI score, preexisting hypertension and diabetes, renal dysfunction, receiving surgery/chemotherapy, anemia and hypoalbuminemia were screened out as the major risk factors of EAD. In-hospital mortality in patients with EAD was 2.1% as compared to those with normal electrolytes (0.3%). The risk of death significantly increased among patients with severe EAD. Similarly, the length of stay and hospital cost also tripled as the number and grade of EAD increased.Conclusion: EAD is commonly encountered in cancer patients and associated with an ominous prognosis. Patients with comorbidities, renal/liver dysfunction, and anti-tumor therapy have a higher risk of EAD. Regular monitoring of electrolytes, optimum regimen for intravenous infusion, timely correction of modifiable factors and appropriate management of EAD should not be neglected during anti-tumor treatment.
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Desequilibrio Ácido-Base/etiología , Costos de Hospital/estadística & datos numéricos , Mortalidad Hospitalaria , Tiempo de Internación/estadística & datos numéricos , Neoplasias/complicaciones , Desequilibrio Hidroelectrolítico/etiología , Desequilibrio Ácido-Base/sangre , Acidosis/sangre , Acidosis/etiología , Anciano , Alcalosis/sangre , Alcalosis/etiología , China , Femenino , Humanos , Hiperpotasemia/etiología , Hipernatremia/etiología , Hipocalcemia/etiología , Hipopotasemia/etiología , Hiponatremia/etiología , Hipofosfatemia/etiología , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Desequilibrio Hidroelectrolítico/sangreRESUMEN
BACKGROUND: This study attempts to establish a Bayesian networks (BNs) based model for inferring the risk of AKI in gastrointestinal cancer (GI) patients, and to compare its predictive capacity with other machine learning (ML) models. METHODS: From 1 October 2014 to 30 September 2015, we recruited 6495 inpatients with GI cancers in a tertiary hospital in eastern China. Data on demographics, clinical and laboratory indicators were retrospectively extracted from the electronic medical record system. Predictors of AKI were selected in gLASSO regression, and further incorporated into BNs analysis. RESULTS: The incidences of AKI in patients with esophagus, stomach, and intestine cancer were 20.5%, 13.9%, and 12.5%, respectively. Through gLASSO, 11 predictors were screened out, including diabetes, cancer category, anti-tumor treatment, ALT, serum creatinine, estimated glomerular filtration rate (eGFR), serum uric acid (SUA), hypoalbuminemia, anemia, abnormal sodium, and potassium. BNs model revealed that cancer category, treatment, eGFR, and hypoalbuminemia had direct connections with AKI. Diabetes and SUA were indirectly linked to AKI through eGFR, and anemia created connections with AKI through affecting album level. Compared with other ML models, BNs model maintained a higher AUC value in both the internal and external validation (AUC: 0.823/0.790). CONCLUSION: BNs model not only delineates the qualitative and quantitative relationship between AKI and its associated factors but shows the more robust generalizability in AKI prediction.
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Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Neoplasias Gastrointestinales/complicaciones , Indicadores de Salud , Anciano , Teorema de Bayes , China/epidemiología , Femenino , Humanos , Incidencia , Pacientes Internos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Análisis de Regresión , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Riesgo , Centros de Atención TerciariaRESUMEN
BACKGROUND: Trimethylamine-N-Oxide (TMAO) is a proatherogenic and prothrombotic metabolite. Our study examined the association of plasma TMAO level with cardiovascular and all-cause mortality in hemodialysis (HD) patients. METHODS: Patients who were at least 18 years-old and received HD for at least 6 months were enrolled within 6 months. Patients with coronary heart disease, congestive heart failure, arrhythmia, or stroke within 3 months before study onset were excluded. The primary endpoints were cardiovascular and all-cause death, and the secondary endpoint was cerebrovascular death. RESULTS: We recruited 252 patients and divided them into a high-TMAO group (>4.73 µg/mL) and a low-TMAO group (≤4.73 µg/mL). The median follow-up time was 73.4 months (interquartile range: 42.9, 108). A total of 123 patients died, 39 from cardiovascular disease, 19 from cerebrovascular disease, and 65 from other causes. Kaplan-Meier analysis indicated that the high-TMAO group had a greater incidence of cardiovascular death (Log-Rank: p = 0.006) and all-cause death (Log-Rank: p < 0.001). Cox regression analysis showed that high TMAO level was significantly associated with cardiovascular and all-cause mortality. After adjustment for confounding, this association remained significant for cardiovascular mortality (TMAO as a continuous variable: HR: 1.18, 95%CI: 1.07, 1.294, p < 0.001; TMAO as a dichotomous variable: HR: 3.44, 95%CI: 1.68, 7.08, p < 0.001) and all-cause mortality (TMAO as a continuous variable: HR: 1.14, 95%CI: 1.08, 1.21, p < 0.001; TMAO as a dichotomous variable: HR: 2.54, 95%CI: 1.71, 3.76, p < 0.001). CONCLUSIONS: High plasma TMAO level is significantly and independently associated with cardiovascular and all-cause mortality in HD patients.
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Enfermedades Cardiovasculares/mortalidad , Fallo Renal Crónico/terapia , Metilaminas/sangre , Diálisis Renal , Adulto , Anciano , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Causas de Muerte , China , Comorbilidad , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Fallo Renal Crónico/sangre , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de RiesgoRESUMEN
AIM: Long non-coding RNA (lncRNAs) have been shown to play a critical role in a variety of pathophysiological processes, such as cell proliferation, apoptosis and migration. However, there were few studies addressing the function of lncRNAs in renal ischaemia/reperfusion (I/R) injury. Apoptosis is an important pathogenesis during I/R injury. Here, we identified the effect of hypoxia-responsive lncRNA growth arrest-specific 5 (GAS5) on apoptosis in renal I/R injury. METHODS: Ischaemia/reperfusion injury in mice or hypoxia/re-oxygenation (H/R) in human proximal renal tubular epithelial cells (HK-2) was practiced to induce apoptosis. The kidneys and blood were collected at 24 h after reperfusion. The GAS5 messenger RNA (mRNA) expression and apoptosis-related gene mRNA and protein levels, including p53, cellular inhibitor of apoptosis protein 2 (cIAP2) and thrombospondin-1 (TSP-1), were analysed. GAS5 small-interfering RNA was transfected with H/R induced cells. Over-expression of GAS5 was performed by plasmid transfection. RESULTS: Apoptotic cells significantly increased in I/R-injured kidneys. GAS5 could be up-regulated in kidneys at 24 h after reperfusion and 3 h after re-oxygenation, combined with increased expression of its downstream apoptosis-related proteins p53 and cIAP2. GAS5 small-interfering RNA treatment down-regulated the mRNA and protein levels of p53 and TSP-1, and attenuated apoptosis induced by H/R in HK-2 cells. Conversely, over-expression of GAS5 up-regulated the mRNA and protein levels of p53 and TSP-1, and promoted apoptosis in HK-2 cells. CONCLUSION: Long non-coding RNA GAS5 induced by I/R injury could promote apoptosis in kidney. TSP-1 might be one of the downstream effectors of GAS5, which will be explored in the future.
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Lesión Renal Aguda/metabolismo , Apoptosis , Túbulos Renales Proximales/metabolismo , ARN Largo no Codificante/metabolismo , Daño por Reperfusión/metabolismo , Lesión Renal Aguda/genética , Lesión Renal Aguda/patología , Animales , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Humanos , Túbulos Renales Proximales/patología , Masculino , Ratones Endogámicos C57BL , ARN Largo no Codificante/genética , Daño por Reperfusión/genética , Daño por Reperfusión/patología , Transducción de Señal , Trombospondina 1/genética , Trombospondina 1/metabolismoRESUMEN
OBJECTIVES: Cumulative fluid overload may influence acute kidney injury (AKI) diagnosis due to the dilution effect. The authors hypothesized a small increase of early postoperative serum creatinine (SCr) adjusted for fluid balance might have superior discrimination ability in subsequent AKI prediction. DESIGN: Retrospective analyses. SETTING: A single-center study in a university hospital. PARTICIPANTS: The study comprised 1,016 adult patients who underwent elective isolated or combined valve surgery in 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics, intraoperative parameters, and intraoperative and postoperative fluid balance were collected through a retrospective chart review. Early postoperative SCr level was drawn within 12 hours of surgical completion and then measured daily. Early relative changes of SCr were categorized as a cutoff value of 10% with or without adjustment for cumulative fluid balance. Kidney Disease: Improving Global Outcomes criteria were used to detect AKI. Logistic analyses were performed to determine risk factors for subsequent AKI with the inclusion of measured or fluid-adjusted early relative changes of SCr, respectively. In this study, 355 patients (34.9%) developed AKI. Multivariate logistic analyses showed age, weight, European System for Cardiac Operative Risk Evaluation II, and cardiopulmonary bypass duration were associated independently with the development of AKI. Model discrimination for AKI prediction was improved significantly when the addition of measured (area under the receiver operating characteristic curve [AUROC] 0.830) and fluid-adjusted early changes of SCr to the basic model (AUROC 0.850). CONCLUSIONS: Early fluid-adjusted relative changes of SCr could improve the predictive ability for subsequent development of AKI in valve surgery patients.
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Lesión Renal Aguda/diagnóstico , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Creatinina/sangre , Complicaciones Posoperatorias/diagnóstico , Lesión Renal Aguda/etiología , Adulto , Anciano , Biomarcadores/sangre , Femenino , Enfermedades de las Válvulas Cardíacas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Equilibrio Hidroelectrolítico/fisiologíaRESUMEN
BACKGROUND/AIMS: Even though delayed ischemic preconditioning (DIPC) has been reported to produce renal protection, the underlying mechanism remains poorly understood. We reported that a 15-minute renal ischemic preconditioning (IPC) 4 days before subsequent ischemia-reperfusion attenuated renal injury Kidney dendritic cells (DCs) are abundant in the renal tubulointerstitium and, depending on their status, can induce immune activation or tolerance. The aim of the present study was to investigate the role of DCs in IPC of the kidney. METHODS: Mouse kidneys were challenged by transient brief episodes of sublethal ischemia followed by subsequent prolonged ischemia. DC abundance and maturation in the spleen and kidney were measured by flow cytometry and immunohistochemical staining. To confirm the function of mature DCs in the renoprotective effect of IPC on renal ischemia-reperfusion injury the A2 adenosine receptor (A2AR) antagonist SCH58261 was administered to stimulate DC maturation prior to assessment of renal functional and histological injury and the inflammatory reaction. RESULTS: Compared with sham-operated animals, preconditioned mice had a reduced injury with less CD11c+ cells, lower levels of the pro-inflammatory cytokine IL-17 and reduced expression of the mature DC marker CCR7. Preconditioned mice also produced more of the anti-inflammatory cytokine IL-10. Both renal cells and splenocytes from these mice had more DCs (CD45+/CD11c+/F4/80-), but fewer of these DCs were mature (CD45+/CD11c+/ F4/80-/MHC-II+/CD80+) compared with those from sham-treated animals, suggesting that the immunomodulatory effect of renal ischemic preconditioning is both local and systemic. Additionally, injection of the A2AR antagonist SCH58261 reversed IPC-induced inhibition of DC maturation and mitigated the protective effect of preconditioning, suggesting that DC maturation contributes to immune cell-mediated ischemic preconditioning. CONCLUSION: Our results show that DIPC of the kidney provides local and systemic immunosuppression by inhibiting DC maturation and hence mediates a renal protective effect.
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Lesión Renal Aguda/terapia , Células Dendríticas/patología , Precondicionamiento Isquémico/métodos , Riñón/patología , Daño por Reperfusión/terapia , Lesión Renal Aguda/inmunología , Lesión Renal Aguda/patología , Animales , Células Dendríticas/inmunología , Terapia de Inmunosupresión/métodos , Interleucina-17/análisis , Interleucina-17/inmunología , Riñón/inmunología , Masculino , Ratones Endogámicos C57BL , Daño por Reperfusión/inmunología , Daño por Reperfusión/patologíaRESUMEN
OBJECTIVE: Sepsis, triggered by microbial infection, is a common and life-threatening systemic illness, often leads to impaired function of vital organs. Ischemic preconditioning induced by transient brief episodes of ischemia is a powerful innate mechanism of organ protection. We have reported that a 15-minute renal ischemic preconditioning substantially attenuated subsequent renal ischemia-reperfusion injury. Here, we investigate whether a brief ischemia and reperfusion in kidney can provide protection at local and remote sites against sepsis-induced organ injury, and whether this protection is microRNA-21 dependent. DESIGN: Laboratory study. SETTING: University laboratory. SUBJECTS: Mouse renal tubular epithelial cells, C57BL/6 J wildtype (Animal Center of Fudan University, Shanghai, China) and microRNA-21-/- mice (B6.129-Mir21atm1Smoc, Shanghai Biomodel Organism Science & Technology Development Co. Shanghai, China). INTERVENTIONS: Mouse renal tubular epithelial cells were treated with hypoxia (2% oxygen). Renal ischemic preconditioning was induced by bilateral renal pedicle clamping for 15 minutes, and sepsis was induced by a single intraperitoneal injection of lipopolysaccharide at a dose of 20 mg/kg or cecal ligation and puncture in mice. MEASUREMENTS AND MAIN RESULTS: Mice treated with renal ischemic preconditioning were protected from endotoxemia or polymicrobial sepsis-induced multiple organ injury, including kidneys, heart, liver, and lungs. Renal ischemic preconditioning induced activation of hypoxia-inducible factor-1α in kidneys, which up-regulated microRNA-21 at transcriptional level, subsequently, leading to increased expression of microRNA-21 in serum exosomes and remote organs, resulting in decreased apoptosis and reduced proinflammatory cytokines production in these organs. In vivo knockdown of microRNA-21 or genetic deletion of microRNA-21 abrogated the organoprotective effects conferred by renal ischemic preconditioning. Mechanistically, we discovered that knockdown of microRNA-21 increased programmed cell death protein 4 expression and nuclear factor-kappa B activity, decreased expression of anti-apoptotic B-cell lymphoma-2. CONCLUSION: MicroRNA-21 is required for local and remote ischemic preconditioning in multiple organ protection against sepsis, and up-regulation of miR-21 may be a potential therapy for sepsis.
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Precondicionamiento Isquémico/métodos , Riñón/irrigación sanguínea , MicroARNs/biosíntesis , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/prevención & control , Sepsis/complicaciones , Animales , Apoptosis/fisiología , Proteínas Reguladoras de la Apoptosis/biosíntesis , Modelos Animales de Enfermedad , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Mediadores de Inflamación/metabolismo , Ratones , Ratones Endogámicos C57BL , FN-kappa B/biosíntesis , Proteínas de Unión al ARN/biosíntesis , Regulación hacia ArribaRESUMEN
BACKGROUND Dysnatremia is a risk factor for poor outcomes. We aimed to describe the prevalence and outcomes of various dysnatremia in hospitalized patients. High-risk patients must be identified to improve the prognosis of dysnatremia. MATERIAL AND METHODS This prospective study included all adult patients admitted consecutively to a university hospital between October 1, 2014 and September 30, 2015. RESULTS All 90 889 patients were included in this study. According to the serum sodium levels during hospitalization, the incidence of hyponatremia and hypernatremia was 16.8% and 1.9%, respectively. Mixed dysnatremia, which was defined when both hyponatremia and hypernatremia happened in the same patient during hospitalization, took place in 0.3% of patients. The incidence of dysnatremia was different in various underlying diseases. Multiple logistic regression analyses showed that all kinds of dysnatremia were independently associated with hospital mortality. The following dysnatremias were strong predictors of hospital mortality: mixed dysnatremia (OR 22.344, 95% CI 15.709-31.783, P=0.000), hypernatremia (OR 13.387, 95% CI 10.642-16.840, P=0.000), and especially hospital-acquired (OR 16.216, 95% CI 12.588-20.888, P=0.000) and persistent (OR 22.983, 95% CI 17.554-30.092, P=0.000) hypernatremia. Hyponatremia was also a risk factor for hospital mortality (OR 2.225, 95% CI 1.857-2.667). However, the OR increased to 56.884 (95% CI 35.098-92.193) if hyponatremia was over-corrected to hypernatremia. CONCLUSIONS Dysnatremia was independently associated with poor outcomes. Hospital-acquired and persistent hypernatremia were strong risk factors for hospital mortality. Effective prevention and proper correction of dysnatremia in high-risk patients may reduce the hospital mortality.
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Mortalidad Hospitalaria , Hospitalización/estadística & datos numéricos , Hipernatremia/mortalidad , Hiponatremia/mortalidad , Anciano , Demografía , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Sodio/sangre , Resultado del TratamientoRESUMEN
BACKGROUND: Mounting evidence indicated that the elevated serum uric acid level was associated with an increased risk of acute kidney injury (AKI). Our goal was to systematically evaluate the correlation of serum uric acid (SUA) level and incidence of AKI by longitudinal cohort studies. METHODS: We searched electronic databases and the reference lists of relevant articles. 18 cohort studies with 75,200 patients were analyzed in this random-effect meta-analysis. Hyperuricemia was defined as SUA levels greater than 360-420 µmol/L (6-7 mg/dl), which was various according to different studies. Data including serum uric acid, serum creatinine, and incidence of AKI and hospital mortality were summarized using random-effects meta-analysis. RESULTS: The hyperuricemia group significantly exerted a higher risk of AKI compared to the controls (odds ratio OR 2.24, 95% CI 1.76-2.86, p < 0.01). Furthermore, there is less difference of the pooled rate of AKI after cardiac surgery between hyperuricemia and control group (34.3% vs 29.7%, OR 1.24, 95% CI 0.96-1.60, p = 0.10), while the rates after PCI were much higher in hyperuricemia group than that in control group (16.0% vs 5.3%, OR 3.24, 95% CI 1.93-5.45, p < 0.01). In addition, there were significant differences in baseline renal function at admission between hyperuricemia and control groups in most of the included studies. The relationship between hyperuricemia and hospital mortality was not significant. The pooled pre-operative SUA levels were higher in AKI group than that in the non-AKI group. CONCLUSIONS: Elevated SUA level showed an increased risk for AKI in patients and measurements of SUA may help identify risks for AKI in these patients.
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Lesión Renal Aguda/epidemiología , Procedimientos Quirúrgicos Cardíacos , Hiperuricemia/epidemiología , Complicaciones Posoperatorias/epidemiología , Mortalidad Hospitalaria , Humanos , Incidencia , Oportunidad Relativa , Factores de RiesgoRESUMEN
BACKGROUND: CD4 T-cell abnormality, influencing the outcome of the maintained hemodialysis (MHD), is common in patients on dialysis. We try to find out factors associated with the activated CD4 T cells, CD4CD69 T cells, to improve the dialysis quality. METHODS: A cross-sectional study was conducted to evaluate the change of CD4CD69 in MHD patients and healthy controls in our hospital from September 2015 to May 2016. A total of 164 MHD patients and 24 healthy controls were included according to the criteria. Univariate and multivariate logistic regression models after correlation analysis were executed to discover the related factors of CD4CD69 T-cell posterior to the division of the CD4CD69 T cell according to its median. RESULTS: The lymphocytes were lower, but the percentage of CD4CD69 T cells was higher in MHD patients compared with healthy controls, even after the propensity score matching based on age and sex. The percentage of CD4 T cells showed no significant difference between the two groups. Further multivariate logistic regression models revealed that CD4CD69 T cell was independently associated with serum total protein (OR 95%CI: 0.830[0.696, 0.990], p = .038), transferrin (OR 95%CI: 3.072[1.131, 8.342], p = .028) and magnesium (OR 95%CI: 16.960[1.030, 279.275], p = .048). CONCLUSION: The percentage of CD4CD69 T cells, activated CD4 T cells, elevated in hemodialysis patients despite the decrease in lymphocytes. The elevated CD4CD69 T cells were independently associated with serum total protein negatively, but transferrin and magnesium positively. Strengthening nutrition, reducing the concentration of transferrin and magnesium might be beneficial to reduce the activation of CD4 T cells and improve the outcome of MHD patients.
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Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Linfocitos T CD4-Positivos/inmunología , Fallo Renal Crónico/inmunología , Lectinas Tipo C/metabolismo , Activación de Linfocitos/inmunología , Diálisis Renal/efectos adversos , Anciano , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/metabolismo , Estudios Transversales , Femenino , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Magnesio/sangre , Masculino , Persona de Mediana Edad , Estado Nutricional , Factores de Riesgo , Transferrina/análisis , Resultado del TratamientoRESUMEN
BACKGROUND: Remote ischemic preconditioning (RIPC) is a promising approach to preventing acute kidney injury (AKI), but its efficacy is controversial. METHODS: A systematic review of 30 randomized controlled trials was conducted to investigate the effects of RIPC on the incidence and outcomes of AKI. Random effects model meta-analyses and meta-regressions were used to generate summary estimates and explore sources of heterogeneity. The primary outcome was incidence of AKI and hospital mortality. RESULTS: The total pooled incidence of AKI in the RIPC group was 11.5 %, significantly less than the 23.3 % incidence in the control group (P = 0.009). Subgroup analyses indicated that RIPC significantly reduced the incidence of AKI in the contrast-induced AKI (CI-AKI) subgroup from 13.5 % to 6.5 % (P = 0.000), but not in the ischemia/reperfusion-induced AKI (IR-AKI) subgroup (from 29.5 % to 24.7 %, P = 0.173). Random effects meta-regression indicated that RIPC tended to strengthen its renoprotective effect (q = 3.95, df = 1, P = 0.047) in these trials with a higher percentage of diabetes mellitus. RIPC had no significant effect on the incidence of stages 1-3 AKI or renal replacement therapy, change in serum creatinine and estimated glomerular filtration rate (eGFR), hospital or 30-day mortality, or length of hospital stay. But RIPC significantly increased the minimum eGFR in the IR-AKI subgroup (P = 0.006) compared with the control group. In addition, the length of ICU stay in the RIPC group was significantly shorter than in the control group (2.6 vs 2.0 days, P = 0.003). CONCLUSIONS: We found strong evidence to support the application of RIPC to prevent CI-AKI, but not IR-AKI.
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Lesión Renal Aguda/prevención & control , Precondicionamiento Isquémico/tendencias , Lesión Renal Aguda/etiología , Lesión Renal Aguda/mortalidad , Humanos , Incidencia , Precondicionamiento Isquémico/métodos , Pruebas de Función Renal , Factores de Riesgo , Procedimientos Quirúrgicos Torácicos/métodos , Procedimientos Quirúrgicos Torácicos/estadística & datos numéricosRESUMEN
OBJECTIVES: To estimate the global incidence and outcomes of acute kidney injury (AKI) after cardiac surgery in adult patients. DESIGN: A systematic review and meta-analysis. SETTING: Cardiac surgery wards. PARTICIPANTS: Adult patients after cardiac surgery INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors searched PubMed, Web of Science, Cochrane Library, OVID, and EMBASE databases for all articles on cardiac surgery patients published during 2004 to 2014. Meta-analyses were conducted to generate pooled incidence, mortality, ICU length of stay, and length of hospital stay. The authors also described the variations according to study design, criteria of AKI, surgical methods, countries, continents, and their economies. After a primary and secondary screen, 91 observational studies with 320,086 patients were identified. The pooled incidence rates of AKI were 22.3% (95% confidence interval [CI], 19.8 to 25.1) in total and 13.6%, 3.8%, and 2.7% at stages 1, 2, and 3, respectively, whereas 2.3% of patients received renal replacement therapy. The pooled short-term and long-term mortality were 10.7% and 30%, respectively, and increased along with the severity of stages. The pooled unadjusted odds ratio for short-term and long-term mortality in patients with AKI relative to patients without AKI was 0.144 (95% CI, 0.108 to 0.192, p<0.001) and 0.342 (95% CI 0.287-0.407, p<0.001), respectively. The pooled average ICU length of stay and length of hospital stay in the AKI group were 5.4 and 15 days, respectively, while they were 2.2 and 10.5 days in the no-AKI group. CONCLUSIONS: AKI is a great burden for patients undergoing cardiac surgery and can affect short-term and long-term prognoses of these patients.
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Lesión Renal Aguda/epidemiología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Salud Global , Complicaciones Posoperatorias/epidemiología , Lesión Renal Aguda/diagnóstico , Adulto , Procedimientos Quirúrgicos Cardíacos/tendencias , Salud Global/tendencias , Humanos , Incidencia , Complicaciones Posoperatorias/diagnóstico , Estudios Prospectivos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: Human papillomavirus type 16 (HPV16) is the cause of more than half of all cases of cervical cancer. Genetic mutations in HPV16 and the integration of HPV16 DNA in the human genome are considered important genetic changes in cervical lesion progression. However, limited data concerning HPV16 lineages and physical integration status have been reported for Shanghai, China. The current study analyzed the genetic mutations in complete HPV16 genomes and the physical integration status of HPV16 DNA. METHODS: A total of 30 samples of cervical exfoliated cells from patients with HPV16 infection were collected. The entire HPV16 genome was isolated, amplified by PCR and directly sequenced. The physical integration status was determined by 3'RACE nested PCR. RESULTS: A total of 13 integration sites were identified, including 9 in common fragile sites and 1 not close to any fragile sites. Phylogenetic analysis identified two HPV lineages: the European (E) lineage and the East Asian (EA) lineage. Amino acid changes of D25E and N29S were the most common variations across the genome. The HPV16 early genes E1 and E7 and the late gene L1 tended to be highly conserved, whereas the early genes E2, E4 and E6 were more variable. Furthermore, 10 novel variations were identified in this study, which led to the 3 amino acid changes of S23I in E2 and E244K and T269I in E2/E4. CONCLUSION: Integrated HPV16 viruses were detected in all stages of cervical samples. Many variants in E2, E4, E7, and the long control region co-varied with E6 variations and helped to define the HPV16 lineages.
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Papillomavirus Humano 16/genética , Proteínas Oncogénicas Virales/genética , Infecciones por Papillomavirus/virología , Adulto , China , Femenino , Papillomavirus Humano 16/aislamiento & purificación , Humanos , Reacción en Cadena de la PolimerasaRESUMEN
Adenomyosis is a benign uterine disorder that is associated with female infertility, a reduced clinical pregnancy rate and a high risk of miscarriage. Solute carrier family 38 member a2 (SLC38A2) is a glutamine (Gln) transporter that serves roles in various medical conditions. The present study aimed to reveal the role of SLC38A2 in adenomyosis. The mRNA expression levels of SLC38A2 in eutopic endometrial (EU) and ectopic endometrial (EC) tissues from adenomyotic patients were examined by reverse transcription-quantitative PCR. EU and EC cell proliferation and invasion were analyzed by Cell Counting Kit-8 and Transwell assays. Changes in the oxygen consumption rate (OCR) were determined to indicate the mitochondrial respiratory function and observed using a Seahorse analyzer. SLC38A2 expression in EC tissues was upregulated compared with that in normal endometrial tissues. SLC38A2 knockdown repressed EC cell proliferation and invasion. In addition, the Gln content and OCR were decreased in EC cells transfected with SLC38A2-knockdown lentivirus, whereas SLC38A2 overexpression had the opposite effect in EU cells. Furthermore, the increased proliferation and invasion rates and Gln level induced by SLC38A2 overexpression in EU cells were alleviated by CB-839, a glutaminase inhibitor. SLC38A2 overexpression promoted Gln metabolism and oxygen consumption rate, resulting in an increase in cell proliferation and invasion in the adenomyosis context. The present study indicated that reduction of SLC38A2 expression could be a novel target for adenomyosis therapy, and SLC38A2 may be a valuable clinical diagnostic molecule for adenomyosis.
RESUMEN
BACKGROUND: Ovarian cancer is a highly lethal gynecologic malignancy. ARHGAP10, a member of Rho GTPase-activating proteins, is a potential tumor suppressor in ovarian cancer. However, its role and the involved mechanism need further examination. Here, we investigated whether ARHGAP10 is also associated with ferroptosis. METHODS: Lentivirus infection was used for gene overexpression or silencing. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to assess mRNA and protein levels, respectively. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Lipid reactive oxygen species level was measured by flow cytometry. A tumorigenicity assay was performed to evaluate tumor growth in vivo, and sections of mouse tumor tissues were examined by immunofluorescence microscopy. Chromatin Immunoprecipitation (ChIP) assay was used to assess the binding of H3K9ac to the promoter region of ARHGAP10. RESULTS: ARHGAP10 overexpression promoted ferroptosis in ovarian cancer cells, resulting in decreased cell viability, and increased lipid reactive oxygen species (ROS) level. Further, it decreased and increased GPX4 and PTGS2 expression, respectively, and also induced suppression of tumor growth in mice. Fer-1, a potent inhibitor of ferroptosis, suppressed the above effects of ARHGAP10. Contrarily, ARHGAP10 silencing alleviated ferroptosis in ovarian cancer cells, which was reversed by RSL3, a ferroptosis-inducing agent. Lastly, sodium butyrate (SB) was found to transcriptionally regulate ARHGAP10, thereby also contributing to the ferroptosis of ovarian cancer cells. CONCLUSIONS: Our results suggest that SB/ARHGAP10/GPX4 is a new signaling axis involved in inducing ferroptosis in ovarian cancer cells and suppressing tumor growth, which has potential clinical significance.