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Aims: This study investigated the regulatory effect of Mitofusin2 (Mfn2) on mitochondria-associated endoplasmic reticulum membrane (MAM) integrity and cellular injury in cisplatin-induced acute kidney injury (CP-AKI). Results: CP-AKI mice exhibited decreased expression of Mfn2, increased expression of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), abnormal mitochondrial morphology, and reduced MAMs integrity, accompanied by the activation of mitochondrial reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress (inositol-requiring enzyme 1 [IRE1] and PERK pathways). In in vitro studies, CP-induced mitochondrial ROS, ER-stress activation, and increased apoptosis were accompanied by the downregulation of Mfn2 and MAMs integrity reduction in Boston University mouse proximal tubular cells (BUMPT) and human proximal tubular epithelial cells (HK-2). Pretreatment of BUMPT cells with the Mfn2 plasmid partially restored the integrity of MAMs, negatively controlled IRE1 and PERK pathways, and inhibited cell apoptosis. In contrast, ER-stress and MAMs integrity violations were increased after Mfn2 small-interfering RNA (siRNA) treatment in HK-2 cells under CP treatment. Coimmunoprecipitation analysis demonstrated that Mfn2 interacted with PERK and IRE1. Furthermore, the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), acadesine (AICAR), had a similar effect to Mfn2 plasmid in the regulation of ER stress and MAMs. Conversely, the ER-stress inhibitor, 4-phenylbutyric acid (4-PBA), had no effect on the expression of Mfn2 and MAMs integrity. Innovation and Conclusion: This is the first study to explore the association between MAMs, ER stress, and Mfn2 in CP-AKI. Downregulation of Mfn2 expression abolished the MAMs integrity, and induced ER stress, mitochondrial ROS, and tubular cell apoptosis. This suggests that the Mfn2-MAMs pathway is a potential therapeutic target in CP-AKI. Antioxid. Redox Signal. 40, 16-39. The Ethical Registration number of animal experiment in this study was CSU-2022-01-0095.

Objectives: To investigate the effects of intravenous hydration in preventing post-contrast outcomes in patients with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m 2 undergoing intravenous administration of iodinated contrast media (ICM)., Methods: Hospitalized patients with eGFR < 30 mL/min/1.73 m 2 and intravenous ICM exposure between 2015 and 2021 were included. Post-contrast outcomes include post-contrast acute kidney injury (PC-AKI) (defined by 2012 Kidney Disease: Improving Global Outcomes (KDIGO) or European Society of Urogenital Radiology (ESUR)), chronic dialysis at discharge, and in-hospital mortality. Confounding effects between the two groups were reduced to a minimum using propensity score-based matching and overlap weighting. Association between intravenous hydration and outcomes was analyzed using logistic regression., Results: In total, 794 patients were included in the study, with 284 receiving intravenous hydration, and 510 not. After 1:1 propensity score matching, 210 pairs were generated. No significant differences were found in the outcomes between the intravenous hydration and no intravenous hydration groups: PC-AKI by KDIGO, 25.2% vs 24.8% (odds ratio (OR), 0.93; 95% confidence interval (CI), 0.57-1.50); PC-AKI by ESUR, 31.0% vs 25.2% (OR, 1.34; 95% CI, 0.86-2.08); chronic dialysis at discharge, 4.3% vs 3.3% (OR, 1.56; 95% CI, 0.56-4.50); in-hospital mortality, 1.9% vs 0.5% (OR, 4.08; 95% CI, 0.58-81.08). Overlap propensity score-weighted analysis also showed no significant effects of intravenous hydration on the incidences of the post-contrast outcomes., Conclusions: Intravenous hydration was not associated with lower risks of PC-AKI, chronic dialysis at discharge, and in-hospital mortality in patients with eGFR < 30 mL/min/1.73 m 2 undergoing intravenous administration of ICM., Clinical Relevance Statement: This study provides new evidence in supporting that intravenous hydration is not beneficial to patients with eGFR < 30 mL/min/1.73 m 2 before and after intravenous administration of iodinated contrast media., Key Points: • Intravenous hydration before and after intravenous administration of ICM is not associated with lower risks in PC-AKI, chronic dialysis at discharge, and in-hospital mortality in patients with eGFR < 30 mL/min/1.73 m 2 . • Withholding intravenous hydration may be considered in patients with eGFR < 30 mL/min/1.73 m 2 around intravenous administration of ICM., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Contrast-induced acute kidney injury (CI-AKI) is a severe complication associated with significant morbidity and mortality, and effective therapeutic strategies are still lacking. Apelin is an endogenous physiological regulator with antioxidative, anti-inflammatory and antiapoptotic properties. However, the role of apelin-13 in CI-AKI remains unclear. In our study, we found that the protein expression levels of apelin were significantly downregulated in rat kidney tissues and HK-2 cells during contrast media treatment. Moreover, we explored the protective effect of apelin-13 on renal tubule damage using in vitro and in vivo models of CI-AKI. Exogenous apelin-13 ameliorated endoplasmic reticulum stress, reactive oxygen species and apoptosis protein expression in contrast media-treated cells and rat kidney tissues. Mechanistically, the downregulation of endoplasmic reticulum stress contributed critically to the antiapoptotic effect of apelin-13. Collectively, our findings reveal the inherent mechanisms by which apelin-13 regulates CI-AKI and provide a prospective target for the prevention of CI-AKI.

Contrast-induced acute kidney injury (CI-AKI), which occurs after the use of iodinated contrast media, has become the third leading cause of hospital-acquired acute kidney injury (AKI). It is associated with prolonged hospitalization and increased risks of end-stage renal disease and mortality. The pathogenesis of CI-AKI is unclear and effective treatments are lacking. By comparing different post-nephrectomy times and dehydration times, we constructed a new, short-course CI-AKI model using dehydration for 24 h two weeks after unilateral nephrectomy. We found that the low-osmolality contrast media iohexol caused more severe renal function decline, renal morphological damage, and mitochondrial ultrastructural alterations compared to the iso-osmolality contrast media iodixanol. The shotgun proteomics based on Tandem Mass Tag (TMT) was used to conduct proteomics research on renal tissue in the new CI-AKI model, and 604 distinct proteins were identified, mainly involving complement and coagulation cascade, COVID-19, PPAR signalling pathway, mineral absorption, cholesterol metabolism, ferroptosis, staphylococcus aureus infection, systemic lupus erythematosus, folate biosynthesis, and proximal tubule bicarbonate reclamation. Then, using parallel reaction monitoring (PRM), we validate 16 candidate proteins, of which five were novel candidates (Serpina1, Apoa1, F2, Plg, Hrg) previously unrelated to AKI and associated with an acute response as well as fibrinolysis. The pathway analysis and 16 candidate proteins may help to discover new mechanisms in the pathogenesis of CI-AKI, allowing for early diagnosis and outcome prediction.

Major adverse kidney events within 30 d (MAKE30) implicates poor outcomes for elderly patients in the intensive care unit (ICU). This study aimed to predict the occurrence of MAKE30 in elderly ICU patients using machine learning. The study cohort comprised 2366 elderly ICU patients admitted to the Second Xiangya Hospital of Central South University between January 2020 and December 2021. Variables including demographic information, laboratory values, physiological parameters, and medical interventions were used to construct an extreme gradient boosting (XGBoost) -based prediction model. Out of the 2366 patients, 1656 were used for model derivation and 710 for testing. The incidence of MAKE30 was 13.8% in the derivation cohort and 13.2% in the test cohort. The average area under the receiver operating characteristic curve of the XGBoost model was 0.930 (95% CI: 0.912-0.946) in the training set and 0.851 (95% CI: 0.810-0.890) in the test set. The top 8 predictors of MAKE30 tentatively identified by the Shapley additive explanations method were Acute Physiology and Chronic Health Evaluation II score, serum creatinine, blood urea nitrogen, Simplified Acute Physiology Score II score, Sequential Organ Failure Assessment score, aspartate aminotransferase, arterial blood bicarbonate, and albumin. The XGBoost model accurately predicted the occurrence of MAKE30 in elderly ICU patients, and the findings of this study provide valuable information to clinicians for making informed clinical decisions.

Land cover changes (LCCs) affect surface temperatures at local scale through biophysical processes. However, previous observation-based studies mainly focused on the potential effects of virtual afforestation/deforestation using the space-for-time assumption, while the actual effects of all types of realistic LCCs are underexplored. Here, we adopted the space-and-time scheme and utilized extensive high-resolution (1-km) satellite observations to perform the first such assessment. We showed that, from 2006 to 2015, the average temperature in the areas with LCCs increased by 0.08 K globally, but varied significantly across latitudes, ranging from -0.05 to 0.18 K. Cropland expansions dominated summertime cooling effects in the northern mid-latitudes, whereas forest-related LCCs caused warming effects elsewhere. These effects accounted for up to 44.6% of overall concurrent warming, suggesting that LCC influences cannot be ignored. In addition, we revealed obvious asymmetries in the actual effects, i.e., LCCs with warming effects occurred more frequently, with stronger intensities, than LCCs with cooling effects. Even for the mutual changes between two covers in the same region, warming LCCs generally had larger magnitudes than their cooling counterparts due to asymmetric changes in transition fractions and driving variables. These novel findings, derived from the assessment of actual LCCs, provide more realistic implications for land management and climate adaptation policies., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2023 Science China Press. Published by Elsevier B.V. All rights reserved.)

Background: Membranous nephropathy (MN) is the leading cause of adult-onset nephrotic syndrome, with primary MN of unclear cause accounting for 80% of cases. Retrospective clinical research reported that MN occurring in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients was triggered by nephrotoxic drugs or of unknown cause. However, whether RA or AS itself increases the risk of developing MN is unknown., Methods: We conducted mendelian randomization (MR) analysis to evaluate the causal effects of RA or AS on MN using genome-wide association study (GWAS) statistics. The inverse variance weighted (IVW) method was the primary analysis, and several supplementary analyses and sensitivity analyses were performed to test the causal estimates., Results: We obtained 30 valid instrumental variables (IVs) of RA and 16 valid IVs of AS from large-scale open-access GWASs. The genetically predicted RA significantly increased the risk of MN [IVW odds ratios (OR) = 1.327, 95% confidence interval (CI) = (1.124, 1.565), P  = 8.051 × 10 -4 ]. Three supplementary MR analyses provided the consistent positive causal effect of RA on MN (all P  < 0.05). No horizontal pleiotropy was detected by MR Egger intercept analysis ( P  = 0.411). However, the genetically predicted AS had no causal effect on MN by IVW and supplementary analysis (all P  > 0.05)., Conclusions: Genetically predicted RA could increase the risk of MN, but genetically predicted AS was not associated with MN. Screening for kidney involvement in RA patients should be noted, and active treatment of RA will reduce the public health burden of MN., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Postoperative acute kidney injury (AKI) is a prevalent condition and associated with increased morbidity and mortality following cardiac surgery. This study aimed to investigate the association of underweight and obesity with adverse postoperative renal outcomes in infants and young children undergoing congenital heart surgery. This retrospective cohort study included patients aged from 1 month to 5 years who underwent congenital heart surgery with cardiopulmonary bypass at the Second Xiangya Hospital of Central South University from January 2016 to March 2022. On the basis of the percentile of body mass index (BMI) for age and sex, eligible participants were divided into three nutritional groups: normal bodyweight, underweight (BMI P5), and obesity (BMI P95). Primary outcomes included postoperative AKI and major adverse kidney events within 30 days (MAKE30). Multivariable logistic regression was performed to determine the association of underweight and obesity with postoperative outcomes. The same analyses were reproduced for classifying patients using weight-for-height instead of BMI. A total of 2,079 eligible patients were included in the analysis, including 1,341 (65%) patients in the normal bodyweight group, 683 (33%) patients in the underweight group, and 55 (2.6%) patients in the obesity group. Postoperative AKI (16% vs. 26% vs. 38%; P < 0.001) and MAKE30 (2.5% vs. 6.4% vs. 9.1%; P < 0.001) were more likely to occur in the underweight and obesity groups. After adjusting for potential confounders, underweight (OR1.39; 95% CI 1.08-1.79; P = 0.008) and obesity (OR 3.85; 95% CI 1.97-7.50; P < 0.001) were found to be associated with an increased risk of postoperative AKI. In addition, both underweight (OR 1.89; 95% CI 1.14-3.14; P = 0.014) and obesity (OR 3.14; 95% CI 1.08-9.09; P = 0.035) were independently associated with MAKE30. Similar results were also found when weight-for-height was used instead of BMI.    Conclusion: In infants and young children undergoing congenital heart surgery, underweight and obesity are independently associated with postoperative AKI and MAKE30. These results may help assess prognosis in underweight and obese patients, and will guide future quality improvement efforts. What is Known: • Postoperative acute kidney injury (AKI) is prevalent and associated with increased morbidity and mortality following pediatric cardiac surgery. • Major adverse kidney events within 30 days (MAKE30) have been recommended as a patient-centered endpoint for evaluating AKI clinical trajectories. A growing concern arises for underweight and obesity in children with congenital heart disease. What is New: • Prevalence of underweight and obesity among infants and young children undergoing congenital heart surgery was 33% and 2.6%, respectively. • Both underweight and obesity were independently associated with postoperative AKI and MAKE30 following congenital heart surgery., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Stratification of chronic kidney disease (CKD) patients [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2] at risk for post-contrast acute kidney injury (PC-AKI) following intravenous administration of iodinated contrast media (ICM) is important for clinical decision-making and clinical trial enrollment., Methods: The derivation and internal validation cohorts originated from the Second Xiangya Hospital. The external validation cohort was generated from the Xiangya Hospital and the openly accessible database Medical Information Mart for Intensive CareIV. PC-AKI was defined based on the serum creatinine criteria of the Kidney Disease: Improving Global Outcomes (KDIGO). Six feature selection methods were used to identify the most influential predictors from 79 candidate variables. Deep neural networks (DNNs) were used to establish the model and compared with logistic regression analyses. Model discrimination was evaluated by area under the receiver operating characteristic curve (AUC). Low-risk and high-risk cutoff points were set to stratify patients., Results: Among 4218 encounters studied, PC-AKI occurred in 10.3, 10.4 and 11.4% of encounters in the derivation, internal and external validation cohorts, respectively. The 14 variables-based DNN model had significantly better performance than the logistic regression model with AUC being 0.939 (95% confidence interval: 0.916-0.958) and 0.940 (95% confidence interval: 0.909-0.954) in the internal and external validation cohorts, respectively, and showed promising discrimination in subgroup analyses (AUC ≥ 0.800). The observed PC-AKI risks increased significantly from the low- to intermediate- to high-risk group (<1.0 to >50%) and the accuracy of patients not developing PC-AKI was 99% in the low-risk category in both the internal and external validation cohorts., Conclusions: A DNN model using routinely available variables can accurately discriminate the risk of PC-AKI of hospitalized CKD patients following intravenous administration of ICM., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a major complication following pediatric cardiac surgery, which is associated with increased morbidity and mortality. The early prediction of CSA-AKI before and immediately after surgery could significantly improve the implementation of preventive and therapeutic strategies during the perioperative periods. However, there is limited clinical information on how to identify pediatric patients at high risk of CSA-AKI., Objective: The study aims to develop and validate machine learning models to predict the development of CSA-AKI in the pediatric population., Methods: This retrospective cohort study enrolled patients aged 1 month to 18 years who underwent cardiac surgery with cardiopulmonary bypass at 3 medical centers of Central South University in China. CSA-AKI was defined according to the 2012 Kidney Disease: Improving Global Outcomes criteria. Feature selection was applied separately to 2 data sets: the preoperative data set and the combined preoperative and intraoperative data set. Multiple machine learning algorithms were tested, including K-nearest neighbor, naive Bayes, support vector machines, random forest, extreme gradient boosting (XGBoost), and neural networks. The best performing model was identified in cross-validation by using the area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using the Shapley additive explanations (SHAP) method., Results: A total of 3278 patients from one of the centers were used for model derivation, while 585 patients from another 2 centers served as the external validation cohort. CSA-AKI occurred in 564 (17.2%) patients in the derivation cohort and 51 (8.7%) patients in the external validation cohort. Among the considered machine learning models, the XGBoost models achieved the best predictive performance in cross-validation. The AUROC of the XGBoost model using only the preoperative variables was 0.890 (95% CI 0.876-0.906) in the derivation cohort and 0.857 (95% CI 0.800-0.903) in the external validation cohort. When the intraoperative variables were included, the AUROC increased to 0.912 (95% CI 0.899-0.924) and 0.889 (95% CI 0.844-0.920) in the 2 cohorts, respectively. The SHAP method revealed that baseline serum creatinine level, perfusion time, body length, operation time, and intraoperative blood loss were the top 5 predictors of CSA-AKI., Conclusions: The interpretable XGBoost models provide practical tools for the early prediction of CSA-AKI, which are valuable for risk stratification and perioperative management of pediatric patients undergoing cardiac surgery., (©Xiao-Qin Luo, Yi-Xin Kang, Shao-Bin Duan, Ping Yan, Guo-Bao Song, Ning-Ya Zhang, Shi-Kun Yang, Jing-Xin Li, Hui Zhang. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 05.01.2023.)

Little is known about whether preventative practices for post-contrast acute kidney injury (PC-AKI) recommended in guidelines have been adopted in clinical practice and translated into a lower incidence of PC-AKI. The aim of this study was to examine the yearly trends in the incidence of PC-AKI, and comorbidities and care practices associated with PC-AKI in hospitalized patients who received intravenous administration of iodinated contrast medium (ICM). Adult patients receiving intravenous ICM at the Second Xiangya Hospital of Central South University in China between 2015 and 2021 were included. Temporal trends in the incidence and risk factors for PC-AKI were evaluated using logistic regression analyses with adjustments for relevant variables. The incidence of PC-AKI has declined significantly from 5.3% in 2015 to 4.1% in 2021 ( p  < 0.001). This decreasing trend persisted after extensive multivariable adjustments. Of the comorbidities associated with PC-AKI, the proportion of patients with congestive heart failure or hypertension increased, while the proportion of patients older than 75 years, or with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m 2 , diabetic nephropathy, or renal stone disease decreased. Among the care practices associated with PC-AKI, the proportion of patients using nephrotoxic drugs decreased, whereas the proportion of patients receiving intravenous fluids > 1000 mL on the day of ICM administration or using iso-osmolar ICM increased. In conclusion, a declining trend in PC-AKI incidence was observed in patients receiving intravenous ICM between 2015 and 2021, which may be related to increased awareness and efforts to prevent PC-AKI.

Renal artery stenosis (RAS) causes severe renovascular hypertension, worsening kidney function, and increased cardiovascular morbidity. According to recent studies, mesenchymal stem cells (MSCs) administration is a promising therapy for the improvement of RAS outcomes. The meta-analysis aims to evaluate the therapeutic effects of MSC therapy on RAS. We performed a search in MEDLINE, Web of Science, Embase, and Cochrane Library from inception to 5, October 2022. We included 16 preclinical and 3 clinical studies in this meta-analysis. In preclinical studies, the pooled results indicated that animals treated with MSCs had lower levels of systolic blood pressure (SBP) (SMD = - 1.019, 95% CI - 1.434 to - 0.604, I 2  = 37.2%, P = 0.000), serum creatinine (Scr) (SMD = - 1.112, 95% CI - 1.932 to - 0.293, I 2  = 72.0%, P = 0.008), and plasma renin activity (PRA) (SMD = - 0.477, 95% CI - 0.913 to 0.042, I 2  = 43.4%, P = 0.032). The studies also revealed increased levels of renal blood flow (RBF) in stenotic kidney (STK) (SMD = 0.774, 95% CI - 0.351 to 1.197, I 2  = 0%, P = 0.000) and the glomerular filtration rate (GFR) of STK (SMD = 1.825, 95% CI 0.963 to 2.688, I 2  = 72.6%, P = 0.000). In clinical studies, the cortical perfusion and fractional hypoxia of the contralateral kidney (CLK) were alleviated by MSC therapy. Taken together, this meta-analysis revealed that MSCs therapy might be a promising treatment for RAS. However, due to the discrepancy between preclinical studies and early clinical trials outcomes, MSC therapy couldn't be recommended in clinical care for the moment, more high-quality randomized controlled clinical trials are needed to validate our conclusions and standardize MSCs protocols., (© 2022. The Author(s).)

An elegant Pd-catalyzed intramolecular Heck dearomative alkenylation of aryl iodides with functionalized N -tosylhydrazones proceeded through a sequential dearomative carbopalladation, migratory insertion, and β-hydride elimination in the presence of Pd(CF 3 COO) 2 (10 mol %), PPh 3 (30 mol %), and Cs 2 CO 3 (2.0 equiv) in 1,4-dioxane (2.0 mL) at 120 °C for 14 h under an argon atmosphere. This cascade cycloaddition protocol provided a reliable and versatile approach to a sequence of structurally diverse indolines in moderate to good yields with good functional group compatibility. In addition, the synthetic robustness of the methodology is highlighted by a scaled-up experiment and derivatization of products via epoxidation and reduction reactions.

Background and Objectives: Acute kidney injury (AKI) that results from ischemia is a common clinical syndrome and correlates with high morbidity and mortality among hospitalized patients. However, a clinical tool to predict mortality risk of ischemic AKI is not available. In this study, we aimed to develop and validate models to predict the 30-day and 1-year mortality risk of hospitalized patients with ischemic AKI., Methods: A total of 1,836 admissions with ischemic AKI were recruited from 277,898 inpatients admitted to three affiliated tertiary general hospitals of Central South University in China between January 2015 and December 2015. Patients in the final analysis were followed up for 1 year. Study patients were randomly divided in a 7:3 ratio to form the training cohort and validation cohort. Multivariable regression analyses were used for developing mortality prediction models., Results: Hepatorenal syndrome, shock, central nervous system failure, Charlson comorbidity index (≥2 points), mechanical ventilation, renal function at discharge were independent risk factors for 30-day mortality after ischemic AKI, while malignancy, sepsis, heart failure, liver failure, Charlson comorbidity index (≥2 points), mechanical ventilation, and renal function at discharge were predictors for 1-year mortality. The area under the receiver operating characteristic curves (AUROCs) of 30-day prediction model were 0.878 (95% confidence interval (CI): 0.849-0.908) in the training cohort and 0.867 (95% CI: 0.820-0.913) in the validation cohort. The AUROCs of the 1-year mortality prediction in the training and validation cohort were 0.803 (95% CI: 0.772-0.834) and 0.788 (95% CI: 0.741-0.835), respectively., Conclusion: Our easily applied prediction models can effectively identify individuals at high mortality risk within 30 days or 1 year in hospitalized patients with ischemic AKI. It can guide the optimal clinical management to minimize mortality after an episode of ischemic AKI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Yan, Zhang, Deng, Luo, Wang and Duan.)

Background: Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients, which is associated with significantly increased mortality. Existing mortality prediction tools showed insufficient predictive power or failed to reflect patients' dynamic clinical evolution. Therefore, the study aimed to develop and validate machine learning-based models for real-time mortality prediction in critically ill patients with SA-AKI., Methods: The multi-center retrospective study included patients from two distinct databases. A total of 12,132 SA-AKI patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) were randomly allocated to the training, validation, and internal test sets. An additional 3,741 patients from the eICU Collaborative Research Database (eICU-CRD) served as an external test set. For every 12 h during the ICU stays, the state-of-the-art eXtreme Gradient Boosting (XGBoost) algorithm was used to predict the risk of in-hospital death in the following 48, 72, and 120 h and in the first 28 days after ICU admission. Area under the receiver operating characteristic curves (AUCs) were calculated to evaluate the models' performance., Results: The XGBoost models, based on routine clinical variables updated every 12 h, showed better performance in mortality prediction than the SOFA score and SAPS-II. The AUCs of the XGBoost models for mortality over different time periods ranged from 0.848 to 0.804 in the internal test set and from 0.818 to 0.748 in the external test set. The shapley additive explanation method provided interpretability for the XGBoost models, which improved the understanding of the association between the predictor variables and future mortality., Conclusions: The interpretable machine learning XGBoost models showed promising performance in real-time mortality prediction in critically ill patients with SA-AKI, which are useful tools for early identification of high-risk patients and timely clinical interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Yan, Duan, Kang, Deng, Liu, Wu and Wu.)

Acute kidney injury (AKI) is common among hospitalized children and is associated with a poor prognosis. The study sought to develop machine learning-based models for predicting adverse outcomes among hospitalized AKI children. We performed a retrospective study of hospitalized AKI patients aged 1 month to 18 years in the Second Xiangya Hospital of Central South University in China from 2015 to 2020. The primary outcomes included major adverse kidney events within 30 days (MAKE30) (death, new renal replacement therapy, and persistent renal dysfunction) and 90-day adverse outcomes (chronic dialysis and death). The state-of-the-art machine learning algorithm, eXtreme Gradient Boosting (XGBoost), and the traditional logistic regression were used to establish prediction models for MAKE30 and 90-day adverse outcomes. The models' performance was evaluated by split-set test. A total of 1394 pediatric AKI patients were included in the study. The incidence of MAKE30 and 90-day adverse outcomes was 24.1% and 8.1%, respectively. In the test set, the area under the receiver operating characteristic curve (AUC) of the XGBoost model was 0.810 (95% CI 0.763-0.857) for MAKE30 and 0.851 (95% CI 0.785-0.916) for 90-day adverse outcomes, The AUC of the logistic regression model was 0.786 (95% CI 0.731-0.841) for MAKE30 and 0.759 (95% CI 0.654-0.864) for 90-day adverse outcomes. A web-based risk calculator can facilitate the application of the XGBoost models in daily clinical practice. In conclusion, XGBoost showed good performance in predicting MAKE30 and 90-day adverse outcomes, which provided clinicians with useful tools for prognostic assessment in hospitalized AKI children., (© 2022. The Author(s).)

Objective: The epidemiology and outcomes of acute kidney disease (AKD) after acute kidney injury (AKI) in hospitalized children are poorly described. The aim of this study is to investigate the prevalence, predictive factors, and clinical outcomes of AKD in hospitalized children with AKI., Methods: Children (1 month-18 years) with AKI during hospitalization in the Second Xiangya Hospital from January 2015 to December 2020 were identified. AKD was defined based on the consensus report of the Acute Disease Quality Initiative 16 workgroup. The endpoints include adverse outcomes in 30 and 90 days. Multivariable logistic regression analyses were used to estimate the odds ratio of 30- and 90-day adverse outcomes associated with AKD and identify the risk factors of AKD., Results: AKD was developed in 42.3% (419/990) of the study patients, with 186 in AKD stage 1, 107 in AKD stage 2, and 126 in AKD stage 3. Pediatric patients with AKD stages 2-3 had significantly higher rates of developing 30- and 90-day adverse outcomes than those with AKD stage 0 and 1. The adjusted odds ratio of AKD stage 2-3 was 12.18 (95% confidence interval (CI), 7.38 - 20.09) for 30-day adverse outcomes and decreased to 2.49 (95% CI, 1.26 - 4.91) for 90-day adverse outcomes. AKI stages 2 and 3, as well as glomerulonephritis, were the only predictive factors for AKD stage 2-3., Conclusion: AKD is frequent among hospitalized pediatric AKI patients. AKD stage 2-3 represents a high-risk subpopulation among pediatric AKI survivors and is independently associated with 30- and 90-day adverse outcomes. Awareness of the potential risks associated with AKD stage 2-3 and its risk factors may help improve outcomes through careful monitoring and timely intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Deng, Yan, Zhang, Luo, Wang and Duan.)

Objectives: To evaluate the effects of intravenous iodinated contrast medium (ICM) administration on the deterioration of renal function (DRF), new renal replacement therapy (RRT) induction and mortality of hospitalized acute kidney injury (AKI) patients., Methods: Adult hospitalized patients undergoing a contrast-enhanced or unenhanced CT scan within 7 days after AKI diagnosis from January 2015 to December 2019 were identified in this retrospective study. Propensity score matching was performed. Outcomes in 7 and 30 days after CT scan were compared between the contrast and non-contrast groups. Additional analyses were also performed in patients stratified by SCr levels at AKI diagnosis, times and time of CT scan, and in patients without chronic kidney disease or RRT requirement prior to CT scan., Results: In total, 1172 pairs were generated after 1:1 propensity score matching from 1336 cases exposed to ICM and 2724 unexposed. No significant differences were found in the outcomes between the two groups: DRF, 7.8% vs 9.0% (odds ratio (OR) 0.83, 95% confidence interval (CI) 0.62-1.11) in 7 days, 5.1% vs 5.4% (OR 0.93, 95%CI 0.64-1.34) in 30 days; new RRT induction, 2.3% vs 3.3% (OR 0.72,95%CI 0.43-1.18) in 7 days, 4.2% vs 4.5% (OR 0.95,95%CI 0.64-1.41) in 30 days; and mortality, 3.9% vs 4.8% (OR 0.83,95%CI 0.56-1.22) in 7 days, 9.0% vs 10.2% (OR 0.88,95%CI 0.68-1.15) in 30 days. Subset analyses showed similar results., Conclusion: Intravenous ICM administration during AKI duration did not increase the risks of DRF, new RRT induction, and mortality in 7 and 30 days after CT scan., Key Points: • Intravenous ICM administration in hospitalized AKI patients does not increase the risks of deterioration of renal function, RRT induction, and mortality in 7 and 30 days after CT scan. • The effects of intravenous ICM on adverse outcomes are minimal even in AKI patients with high level of SCr values or multiple CT scans., (© 2021. European Society of Radiology.)

When expressing streptavidin recombinant polypeptide on magnetosomes (called bacterial magnetic nanoparticles, or BMPs), the presence of endogenous bacterial biotin might be detrimental. In the study, the streptavidin monomer fragment (S1-116) was fused with the intein N-terminal (termed precursor S1-116-IN), and S1-116-IN was expressed in E. coli (BL21). Meanwhile, the SA117-160 fragment was fused with the C-terminal intein, and then this chimeric polypeptide was expressed on magnetosomes by fusion with magnetosome membrance protein MamF. In the in vitro protein splicing system, the purified engineered magnetosomes (BMP-SA117-160-IC) and the S1-116-IN precursor were mixed. Intein-mediated trans-splicing reaction was induced to produce the functional magnetic beads BMP-SA. Our results indicate that intein-mediated protein trans-splicing may lead to efficient synthesis of the recombinant streptavidin on the magnetosomes, showing its promising potential to produce other functional magnetic nanoparticles.

Acute kidney injury (AKI) is commonly present in critically ill patients with sepsis. Early prediction of short-term reversibility of AKI is beneficial to risk stratification and clinical treatment decision. The study sought to use machine learning methods to discriminate between transient and persistent sepsis-associated AKI. Septic patients who developed AKI within the first 48 h after ICU admission were identified from the Medical Information Mart for Intensive Care III database. AKI was classified as transient or persistent according to the Acute Disease Quality Initiative workgroup consensus. Five prediction models using logistic regression, random forest, support vector machine, artificial neural network and extreme gradient boosting were constructed, and their performance was evaluated by out-of-sample testing. A simplified risk prediction model was also derived based on logistic regression and features selected by machine learning algorithms. A total of 5984 septic patients with AKI were included, 3805 (63.6%) of whom developed persistent AKI. The artificial neural network and logistic regression models achieved the highest area under the receiver operating characteristic curve (AUC) among the five machine learning models (0.76, 95% confidence interval [CI] 0.74-0.78). The simplified 14-variable model showed adequate discrimination, with the AUC being 0.76 (95% CI 0.73-0.78). At the optimal cutoff of 0.63, the sensitivity and specificity of the simplified model were 63% and 76% respectively. In conclusion, a machine learning-based simplified prediction model including routine clinical variables could be used to differentiate between transient and persistent AKI in critically ill septic patients. An easy-to-use risk calculator can promote its widespread application in daily clinical practice., (© 2021. The Author(s).)

Acute kidney injury (AKI) correlates with increased health-care costs and poor outcomes in older adults. However, there is no good scoring system to predict mortality within 30-day, 1-year after AKI in older adults. We performed a retrospective analysis screening data of 53,944 hospitalized elderly patients (age > 65 years) from multi-centers in China. 944 patients with AKI (acute kidney disease) were included and followed up for 1 year. Multivariable regression analysis was used for developing scoring models in the test group (a randomly 70% of all the patients). The established models have been verified in the validation group (a randomly 30% of all the patients). Model 1 that consisted of the risk factors for death within 30 days after AKI had accurate discrimination (The area under the receiver operating characteristic curves, AUROC: 0.90 (95% CI 0.875-0.932)) in the test group, and performed well in the validation groups (AUROC: 0.907 (95% CI 0.865-0.949)). The scoring formula of all-cause death within 1 year (model 2) is a seven-variable model including AKI type, solid tumor, renal replacement therapy, acute myocardial infarction, mechanical ventilation, the number of organ failures, and proteinuria. The area under the receiver operating characteristic (AUROC) curves of model 2 was > 0.80 both in the test and validation groups. Our newly established risk models can well predict the risk of all-cause death in older hospitalized AKI patients within 30 days or 1 year., (© 2021. The Author(s).)

Background: Acute kidney injury (AKI) and chronic kidney disease (CKD) have become worldwide public health problems, but little information is known about the epidemiology of acute kidney disease (AKD)-a state in between AKI and CKD. We aimed to explore the incidence and outcomes of hospitalized patients with AKD after AKI, and investigate the prognostic value of AKD in predicting 30-day and one-year adverse outcomes., Methods: A total of 2,556 hospitalized AKI patients were identified from three tertiary hospitals in China in 2015 and followed up for one year.AKD and AKD stage were defined according to the consensus report of the Acute Disease Quality Initiative 16 workgroup. Multivariable regression analyses adjusted for confounding variables were used to examine the association of AKD with adverse outcomes., Results: AKD occurred in 45.4% (1161/2556) of all AKI patients, 14.5% (141/971) of AKI stage 1 patients, 44.6% (308/691) of AKI stage 2 patients and 79.6% (712/894) of AKI stage 3 patients. AKD stage 1 conferred a greater risk of Major Adverse Kidney Events within 30 days (MAKE30) (odds ratio [OR], 2.36; 95% confidence interval 95% CI [1.66-3.36]) than AKD stage 0 but the association only maintained in AKI stage 3 when patients were stratified by AKI stage. However, compared with AKD stage 0, AKD stage 2-3 was associated with higher risks of both MAKE30 and one-year chronic dialysis and mortality independent of the effects of AKI stage with OR being 31.35 (95% CI [23.42-41.98]) and 2.68 (95% CI [2.07-3.48]) respectively. The association between AKD stage and adverse outcomes in 30 days and one year was not significantly changed in critically ill and non-critically ill AKI patients. The results indicated that AKD is common among hospitalized AKI patients. AKD stage 2-3 provides additional information in predicting 30-day and one-year adverse outcomes over AKI stage. Enhanced follow-up of renal function of these patients may be warranted., Competing Interests: The authors declare there are no competing interests., (©2021 Yan et al.)

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are a promising tool to attenuate cisplatin (CP)-induced acute kidney injury (AKI). However, whether the transplantation of human cord blood mononuclear cells (hCBMNCs) exhibits similar protective effects and their potential underlying mechanisms of action remain unclear. The present study aimed to determine the protective effects of hUCMSCs and hCBMNCs transplantation therapies on an established CP-induced rat model and explore their underlying mechanisms of action. A total of 24 Sprague-Dawley rats, selected based on body weight, were randomly assigned into 4 groups: i) normal control; ii) model (CP); iii) hCBMNCs (CP + hCBMNCs); and iv) hUCMSCs (CP + hUCMSCs). hUCMSCs (2.0x10 6 cells) and hCBMNCs (2.0x10 6 cells) were injected into the femoral vein of rats 24 h after CP (8 mg/kg) treatment. To determine the effects of hCBMNCs and hUCMSCs on CP-induced rats, renal function assessment and histological evaluations were performed. Expression levels of high mobility group box 1 (HMGB1) and the ratio of Bax/Bcl2 in renal tissues were detected to elucidate their underlying molecular mechanisms of action. The results demonstrated that transplantation of hUCMSCs and hCBMNCs significantly improved renal function in CP-induced AKI rats, as evidenced by the enhancement of renal morphology; decreased concentrations of blood urea nitrogen and serum creatinine; and a lower percentage of apoptotic renal tubular cells. The expression of HMGB1 and the ratio of Bax/Bcl-2 were significantly reduced in the hUCMSCs and hCBMNCs groups compared with CP group. In conclusion, the present study indicated that hCBMNCs exert similar protective effects to hUCMSCs on CP-induced AKI. hUCMSCs and hCBMNCs protect against CP-induced AKI by suppressing HMGB1 expression and preventing cell apoptosis., (Copyright: © Xu et al.)

Acute kidney disease (AKD) is a state between acute kidney injury (AKI) and chronic kidney disease (CKD), but the prognosis of AKD is unclear and there are no risk-prediction tools to identify high-risk patients. 2,556 AKI patients were selected from 277,898 inpatients of three affiliated hospitals of Central South University from January 2015 to December 2015. The primary point was whether AKI patients developed AKD. The endpoint was death or end stage renal disease (ESRD) 90 days after AKI diagnosis. Multivariable Cox regression was used for 90-day mortality and two prediction models were established by using multivariable logistic regression. Our study found that the incidence of AKD was 53.17% (1,359/2,556), while the mortality rate and incidence of ESRD in AKD cohort was 19.13% (260/1,359) and 3.02% (41/1,359), respectively. Furthermore, adjusted hazard ratio of mortality for AKD versus no AKD was 1.980 (95% CI 1.427-2.747). In scoring model 1, age, gender, hepatorenal syndromes, organic kidney diseases, oliguria or anuria, respiratory failure, blood urea nitrogen (BUN) and acute kidney injury stage were independently associated with AKI progression into AKD. In addition, oliguria or anuria, respiratory failure, shock, central nervous system failure, malignancy, RDW-CV ≥ 13.7% were independent risk factors for death or ESRD in AKD patients in scoring model 2 (goodness-of fit, P 1  = 0.930, P 2  = 0.105; AUROC 1  = 0.879 (95% CI 0.862-0.896), AUROC 2  = 0.845 (95% CI 0.813-0.877), respectively). Thus, our study demonstrated AKD was independently associated with increased 90-day mortality in hospitalized AKI patients. A new prediction model system was able to predict AKD following AKI and 90-day prognosis of AKD patients to identify high-risk patients.

Background: Acute kidney injury (AKI) is one of the common complications of sepsis. Heretofore, there is no effective treatment for septic AKI. Recent studies have revealed that besides treating hematological malignancies, human umbilical cord blood mononuclear cells (hUCBMNCs) show good therapeutic effects on other diseases. But whether hUCBMNCs can protect against septic AKI and its underlying mechanism are unknown., Methods: The rat model of lipopolysaccharide- (LPS-) induced AKI was developed, and the injection of hUCBMNCs was executed to prevent and treat AKI. ML385, a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor, was used to silence Nrf2. The cell experiments were conducted to elaborate the protective mechanism of Nrf2 pathway., Results: An effective model of LPS-induced AKI was established. Compared to the rats only with LPS injection, the levels of inflammation, reactive oxygen species (ROS), and apoptosis in renal tissues after hUCBMNC injection were markedly attenuated. Pathological examination also indicated significant remission of renal tissue injury in the LPS+MNCs group, compared to rats in the LPS group. Transmission electron microscopy (TEM) showed that the damage of the mitochondria in the LPS+MNCs group was lighter than that in the LPS group. Noteworthily, the renal Nrf2/HO-1 pathway was activated and autophagy was enhanced after hUCBMNC injection. ML385 could partly reverse the renoprotective effect of hUCBMNCs, which could demonstrate that Nrf2 participated in the protection of hUCBMNCs. Cell experiments showed that increasing the expression level of Nrf2 could alleviate LPS-induced cell injury by increasing the autophagy level and decreasing the injury of the mitochondria in HK-2 cells., Conclusion: All results suggest that hUCBMNCs can protect against LPS-induced AKI via the Nrf2 pathway. Activating Nrf2 can upregulate autophagy to protect LPS-induced cell injury., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Li-Xin Feng et al.)

Objectives: To investigate the prognosis including major adverse kidney events within 30 days (MAKE30) and 90-day and 1-year adverse outcome in hospitalized patients with post-contrast acute kidney injury (PC-AKI) to identify high-risk factors., Methods: This retrospective observational study included 288 PC-AKI patients selected from 277,898 patients admitted to hospitals from January 2015 to December 2015. PC-AKI was defined according to the 2018 guideline of European Society of Urogenital Radiology. Multivariable Cox regression and logistic regression analyses were used to analyze main outcome and risk factors., Results: PC-AKI patients with AKI stage ≥ 2 had much higher incidence of MAKE30 than those with AKI stage 1 (RR = 7.027, 95% CI 4.918-10.039). Persistent renal dysfunction, heart failure, central nervous system failure, baseline eGFR < 60 mL/min/1.73 m 2 , oliguria or anuria, blood urea nitrogen ≥ 7.14 mmol/L, respiratory failure, and shock were independent risk factors of 90-day or 1-year adverse prognosis (p < 0.05). Compared with transient renal dysfunction, PC-AKI patients with persistent renal dysfunction had a higher all-cause mortality rate (RR = 3.768, 95% CI 1.612-8.810; RR = 4.106, 95% CI 1.765-9.551) as well as combined endpoints of death, chronic kidney disease, or end-stage renal disease (OR = 3.685, 95% CI 1.628-8.340; OR = 5.209, 95% CI 1.730-15.681) within 90 days or 1 year., Conclusions: PC-AKI is not always a transient, benign creatininopathy, but can result in adverse outcome. AKI stage is independently correlated to MAKE30 and persistent renal dysfunction may exaggerate the risk of long-term adverse events., Key Points: • PC-AKI can result in adverse outcome such as persistent renal dysfunction, dialysis, chronic kidney disease (CKD), end-stage renal disease (ESRD), or death. • AKI stage is independently correlated to MAKE30. • Persistent renal dysfunction may exaggerate the risk of long-term adverse events.

Contrast-induced acute kidney injury (CI-AKI) is the third common cause of acute kidney injury (AKI), which is associated with poor short- and long-term outcomes. Currently, effective therapy strategy for CI-AKI remains lacking. Stanniocalcin-1 (STC1) is a conserved glycoprotein with antiapoptosis and anti-inflammatory functions, but the role of STC1 in controlling CI-AKI is unknown. Here, we demonstrated a protective role of STC1 in contrast-induced injury in cultured renal tubular epithelial cells and CI-AKI rat models. Recombinant human STC1 (rhSTC1) regulated mitochondrial quality control, thus suppressing contrast-induced mitochondrial damage, oxidative stress, inflammatory response, and apoptotic injury. Mechanistically, activation of the Nrf2 signaling pathway contributes critically to the renoprotective effect of STC1. Together, this study demonstrates a novel role of STC1 in preventing CI-AKI and reveals Nrf2 as a molecular target of STC1. Therefore, this study provides a promising preventive target for the treatment of CI-AKI., Competing Interests: There were no potential conflicts of interest that needed to be disclosed., (Copyright © 2020 Fei Zhao et al.)

Currently, there is no effective method to prevent renal interstitial fibrosis after acute kidney injury (AKI). In this study, we established and screened a new renal interstitial fibrosis rat model after cisplatin-induced AKI. Our results indicated that rats injected with 4 mg/kg cisplatin once a week for two weeks after firstly administrated with 6.5 mg/kg loading dose of cisplatin could set up a more accurate model reflecting AKI progression to renal interstitial fibrosis. Then, we investigated the effects and possible mechanisms of human umbilical cord blood mononuclear cells (hUCBMNCs) on renal tubular interstitial fibrosis after cisplatin-induced AKI. In rats injected with hUCBMNCs for four times, level of matrix metalloproteinase 7(MMP-7)in serum and urine, urinary albumin/creatinine ratio, tubular pathological scores, the relative collagen area of the tubulointerstitial region, endoplasmic reticulum dilation and the mitochondrial ultrastructural damage were significantly improved. The level of reactive oxygen species, α-smooth muscle actin (α-SMA), [NOD]-like pyrin domain containing protein 3 and cleaved-Caspase 3 in renal tissue decreased significantly. However, in rats injected with hUCBMNCs for two times, no significant difference was discovered in MMP-7 levels and urinary albumin/creatinine ratio. Although expression of α-SMA and the percentage areas of collagen staining in tubulointerstitial tissues were ameliorated in rats injected with hUCBMNCs for two times, the effects were significantly weaker than those in rats injected with hUCBMNCs for four times. Taken together, our study constructed a highly efficient, duplicable novel rat model of renal fibrosis after cisplatin-induced AKI. Multiple injections of hUCBMNCs may prevent renal interstitial fibrosis after cisplatin-induced AKI., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Aim: The purpose of this study is to observe the volume change of prostate and laser-ablated lesions in the canine and to explore the mechanism and clinical significance through histopathology., Materials and Methods: Transperineal laser ablation (TPLA) was performed under the guidance of transrectal ultrasound (TRUS) in eight canines. Two canines were sacrificed 1 day and 1 week after TPLA, respectively. The remaining six canines were sacrificed after finishing transrectal contrast-enhanced ultrasound (TR-CEUS) at three phases., Results: The prostatic volumes immediately following TPLA and 1 week later were larger than before TPLA (20.1 ± 3.9 vs 17.1 ± 3.8 ml; 21.7 ± 3.6 vs 17.1 ± 3.8 ml, p  < 0.05), but 1 month later, returned to the preoperative level (17.4 ± 3.2 ml). At three time points, the mean volumes of laser-ablated lesions at 3 W/600 J were 0.6 ± 0.2, 1.1 ± 0.4, and 1.7 ± 0.5 ml, respectively, while those of laser-ablated lesions at 3 W/1200 J were 1.2 ± 0.2, 1.6 ± 0.3, and 2.2 ± 0.5 ml, respectively. The mean volumes of laser-ablated lesions increased significantly over time after TPLA ( p  < 0.050)., Conclusion: The prostate volume transient enlarges after TPLA, which prompts for clinical application that it should prolong appropriately the duration of urinary catheterization to avoid acute urinary retention. Many inflammatory cells were observed in the laser-ablated lesions and adjacent normal prostate parenchyma through histopathology. It is speculated that the inflammatory response is involved in the progression of tissue damage.

Contrast-induced acute kidney injury (CI-AKI) is a severe complication of intravascular applied radial contrast media, and recent progress in interventional therapy and angiography has revived interest in explaining detailed mechanisms and developing effective treatment. Recent studies have indicated a potential link between CI-AKI and microRNA (miRNA). However, the potential non-coding RNA-associated-competing endogenous RNA (ceRNA) pairs involved in CI-AKI still remain unclear. In this study, we systematically explored the circRNA or lncRNA-associated-ceRNA mechanism in a new rat model of CI-AKI through deep RNA sequencing. The results revealed that the expression of 38 circRNAs, 12 lncRNAs, 13 miRNAs and 127 mRNAs were significantly dysregulated. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses for mRNAs with significantly different expression and then constructed comprehensive circRNA or lncRNA-associated ceRNA networks in kidney of CI-AKI rats. Thereafter, two constructed ceRNA regulatory pathways in this CI-AKI rat model-novel&#95;circ&#95;0004153/rno-miR-144-3p/Gpnmb or Naglu and LNC&#95;000343/rno-miR-1956-5p/KCP-were validated by real-time qPCR. This study is the first one to provide a systematic dissection of non-coding RNA-associated ceRNA profiling in kidney of CI-AKI rats. The selected non-coding RNA-associated ceRNA networks provide new insight for the underlying mechanism and may profoundly affect the diagnosis and therapy of CI-AKI., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Contrast-induced acute kidney injury (CI-AKI) is a major adverse effect caused by intravascular administration of iodinated contrast medium. Whether there is a difference in CI-AKI incidence between iso-osmolar (IOCM) and low-osmolar contrast media (LOCM) among diabetic patients is controversial., Methods: Randomized controlled trials comparing the nephrotoxic effects between IOCM and LOCM in diabetic patients with or without CKD (eGFR< 60 ml/min/1.73 m 2 ) were included in the analysis. The incidence of CI-AKI was defined as an initial increase in serum creatinine (SCr) concentration of at least 0.5 mg/dl or a rise in creatinine of 25% from baseline., Results: A total of 2190 patients were included, among whom 1122 patients received IOCM and 1068 received LOCM. When compared to LOCM, IOCM had no significant benefit in preventing CI-AKI (OR = 1.66, [CI: 0.97-2.84], P = 0.06, I 2  = 54%). However, the difference between IOCM and LOCM was found when CI-AKI was defined as an absolute SCr increase (≥0.5 mg/dl) rather than a relative SCr increase (≥25%). Further analysis showed that LOCM resulted in more adverse events., Conclusions: Whether there is a difference of CI-AKI incidence between IOCM and LOCM in diabetic patients was related to the selected diagnostic criteria. The incidence of adverse events was significantly lower with IOCM when compared with LOCM. Therefore, we suggest that IOCM may be used in diabetic and CKD (eGFR< 60 ml/min/1.73 m 2 ) patients.

Recent progress in angiography and interventional therapy has revived interest in comparison of nephrotoxicity of low-or iso-osmolar contrast media, but detailed mechanisms and effective treatments of contrast-induced acute kidney injury (CI-AKI) remain elusive. We established a new model of CI-AKI and compared the nephrotoxicity of iohexol and iodixanol with a focus on renal oxidative stress, mitochondrial damage and mitophagy. Our results showed that 48-h dehydration plus furosemide injection before iohexol administration successfully induced CI-AKI in rats. Compared with iodixanol, iohexol induced a greater decrease in renal function, more severe morphological damage and mitochondrial ultrastructural changes, an increased number of apoptotic cells, decreased antioxidative enzymes with activation of NLRP3 inflammasome in renal tissue. Renal contrast media kinetics showed the immediate excretion of iohexol and the transient renal accumulation of iodixanol. Plasma mtDNA Tc numbers were positively correlated with markers of renal mitochondrial disruption but negatively correlated with the level of serum creatinine and the score of tubular injury. Of note, iodixanol appeared to induce a stronger activation of mitophagy than iohexol, evidenced by greater protein levels of LC3II and PINK1/Parkin in the renal tissue of iodixanol-treated rats. Taken together, our results indicate that iohexol induced more severe nephrotoxicity than iodixanol in vivo due to apoptosis, destruction of antioxidative defense machinery, activation of NLRP3 inflammasome, mitochondrial damage and mitophagy. Plasma mtDNA may serve as a biological marker for renal mitochondrial disruption and damage in CI-AKI. Antioxidative defense and mitophagy are involved in the process of CI-AKI and may be promising targets of therapies.

Background/aims: Contrast induced-acute kidney injury (CI-AKI) is one of the most common causes of acute kidney injury (AKI) in hospitalized patients. Mitophagy, the selective elimination of mitochondria via autophagy, is an important mechanism of mitochondrial quality control in physiological and pathological conditions. In this study, we aimed to determine effects of iohexol and iodixanol on mitochondrial reactive oxygen species (ROS), mitophagy and the potential role of mitophagy in CI-AKI cell models., Methods: Cell viability was measured by cell counting kit-8. Cell apoptosis, mitochondrial ROS and mitochondrial membrane potential were detected by western blot, MitoSOX fluorescence and TMRE staining respectively. Mitophagy was detected by the colocalization of LC3-FITC with MitoTracker Red, western blot and electronic microscope., Results: The results showed that mitophagy was induced in human renal tubular cells (HK-2 cells) under different concentrations of iodinated contrast media. Mitochondrial ROS displayed increased expression after the treatment. Rapamycin (Rap) enhanced mitophagy and alleviated contrast media induced HK-2 cells injury. In contrast, autophagy inhibitor 3-methyladenine (3-MA) down-regulated mitophagy and aggravated cells injury., Conclusions: Together, our finding indicates that iohexol and iodixanol contribute to the generation of mitochondrial ROS and mitophagy. The enhancement of mitophagy can effectively protect the kidney from iodinated contrast (iohexol)-induced renal tubular epithelial cells injury., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

With the steady increase in the use of various contrast‑related technologies in recent years, contrast‑induced nephropathy has received significant attention from clinicians and researchers. The present study aimed to determine the potential role of autophagy in iodinated contrast media (CM)‑induced cell injury and apoptosis in human proximal renal tubular epithelial HK‑2 cells. The present study used the iodinated CM iohexol (200 mg iodine/ml) to treat HK‑2 cells for 6 h, in order to establish a damaged cell model. The autophagy inhibitor 3‑methyladenine (3‑MA; 10 mM) was used to inhibit the formation of autophagosomes. Immunofluorescence assay and transmission electron microscopy (TEM) were used to observe the formation of autophagosomes in the cytoplasm. The protein expression levels of microtubule‑associated protein 1A/1B‑light chain 3 (LC3)‑II and autophagy‑related protein 7 (Atg7) were detected by western blotting. The cytotoxicity of CM was evaluated by MTT assay and lactate dehydrogenase release, and cell apoptosis was detected by flow cytometry. Increased formation of autophagosomes and autophagic vesicles was observed under TEM in HK‑2 cells following iohexol treatment for 6 h. Immunofluorescence assay demonstrated that iohexol increased LC3‑II expression in HK‑2 cells. Furthermore, the expression levels of LC3‑II and Atg7 in HK‑2 cells were significantly upregulated by iohexol administration; however, LC3‑II and Atg7 expression was decreased by 3‑MA treatment. These results provided evidence to suggest that autophagy is activated in response to iohexol‑induced cell injury and apoptosis, and may exert a renoprotective role in HK‑2 cells.

Contrast media (CM)-induced nephropathy (CIN) is a serious complication of intravascularly applied radiocontrast media. At present, no drugs have been approved for the prevention of CIN. The present study aimed to explore the effects and potential mechanisms of atorvastatin on iodinated CM-induced cytotoxicity in the human proximal renal tubular epithelial cells. The cytotoxic effect of iohexol (50, 100 and 200 mg I/ml) and the protective effect of atorvastatin pretreatment (1, 20 and 40 µM) were assessed. The cytotoxicity of iohexol was evaluated via the MTT cell viability and lactate dehydrogenase assays. The amount of apoptotic cells was determined by flow cytometry. Morphological changes in HK-2 cells were observed via transmission electron microscopy. The mRNA expression of NOX4 and p22phox was measured through reverse transcription-quantitative polymerase chain reaction analysis. The cytotoxicity was induced by iohexol in HK-2 cells. Atorvastatin was identified to significantly alleviate the suppression of cell viability induced by iohexol. Notably, 40 µM atorvastatin also significantly reduced the mRNA expression of intracellular NOX4 and p22phox, and the percentage of apoptotic cells. Furthermore, morphological changes characteristic of injured cells were alleviated by atorvastatin pretreatment. These results suggest that atorvastatin exhibits a protective effect on HK-2 cells against iohexol-induced cytotoxicity through the downregulation of NOX4 and p22phox. Thus, atorvastatin is a potential therapeutic agent for the prevention of CIN and required further study.

Background: Iodiated contrast-induced nephropathy (CIN) is a serious complication of contrast-enhanced imaging. The aim of this study was to evaluate the diagnostic sensitivities and specificities of serum cystatin C (sCys C) and serum creatinine (sCr) for CIN and to further investigate difference of the incidence, risk factors, and in-hospital and 3-month prognosis of CIN according to sCys C criteria and sCr criteria., Methods: We prospectively evaluated 213 patients who underwent angiography. The sCr and sCys C concentrations were detected before and at 48 hours, 72 hours after the procedure. The incidence, risk factors, and in-hospital and 3-month prognosis of CIN were analyzed. Receiver operating characteristic curve (ROC) analysis was performed for sCr and sCys C 48 hours after procedure., Results: The incidence of CIN was 24.4% (sCys C criteria) and 8% (sCr criteria). Diabetes mellitus, dehydration, and hypoalbuminemia were independent risk factors for CIN. Area under the ROC of sCys C 48 hours after procedure was not superior to sCr (0.715 vs 0.790, P=.178). The mortality of patients with CIN in sCr criteria increased significantly (P<.05)., Conclusion: In this study, the incidence and risk factors of CIN were related to diagnostic criteria. The sCys C was not superior to sCr for predicting CIN in the patients who underwent angiography., (© 2016 Wiley Periodicals, Inc.)

Currently, little information is available to stratify the risks and predict acute kidney injury (AKI)-associated death. In this present cross-sectional study, a novel scoring model was established to predict the probability of death within 90 days in patients with AKI diagnosis. For establishment of predictive scoring model, clinical data of 1169 hospitalized patients with AKI were retrospectively collected, and 731 patients of them as the first group were analyzed by the method of multivariate logistic regression analysis to create a scoring model and further predict patient death. Then 438 patients of them as the second group were used for validating this prediction model according to the established scoring method. Our results showed that Patient's age, AKI types, respiratory failure, central nervous system failure, hypotension, and acute tubular necrosis-individual severity index (ATN-ISI) score are independent risk factors for predicting the death of AKI patients in the created scoring model. Moreover, our scoring model could accurately predict cumulative AKI and mortality rate in the second group. In conclusion, this study identified the risk factors of 90-day mortality for hospitalized AKI patients and established a scoring model for predicting 90-day prognosis, which could help to interfere in advance for improving the quality of life and reduce mortality rate of AKI patients.

An analysis of the atmospheric impact on ground brightness temperature (Tg) is performed for numerous land surface types at commonly-used frequencies (i.e., 1.4 GHz, 6.93 GHz, 10.65 GHz, 18.7 GHz, 23.8 GHz, 36.5 GHz and 89.0 GHz). The results indicate that the atmosphere has a negligible impact on Tg at 1.4 GHz for land surfaces with emissivities greater than 0.7, at 6.93 GHz for land surfaces with emissivities greater than 0.8, and at 10.65 GHz for land surfaces with emissivities greater than 0.9 if a root mean square error (RMSE) less than 1 K is desired. To remove the atmospheric effect on Tg, a generalized atmospheric correction method is proposed by parameterizing the atmospheric transmittance τ and upwelling atmospheric brightness temperature Tba↑. Better accuracies with Tg RMSEs less than 1 K are achieved at 1.4 GHz, 6.93 GHz, 10.65 GHz, 18.7 GHz and 36.5 GHz, and worse accuracies with RMSEs of 1.34 K and 4.35 K are obtained at 23.8 GHz and 89.0 GHz, respectively. Additionally, a simplified atmospheric correction method is developed when lacking sufficient input data to perform the generalized atmospheric correction method, and an emissivity-based atmospheric correction method is presented when the emissivity is known. Consequently, an appropriate atmospheric correction method can be selected based on the available data, frequency and required accuracy. Furthermore, this study provides a method to estimate τ and Tba↑ of different frequencies using the atmospheric parameters (total water vapor content in observation direction Lwv, total cloud liquid water content Lclw and mean temperature of cloud Tclw), which is important for simultaneously determining the land surface parameters using multi-frequency passive microwave satellite data.

Background: The distribution of the Mur blood group antigen is 5-7% in the south of China, and a much higher prevalence is observed in some areas of the region. Anti-Mur can cause hemolytic disease of the newborn and severe transfusion reactions., Objectives: Genetic testing is more ideal than conventional serological tests because antibodies for detection are usually not available., Methods: In this study, a novel loop-mediated isothermal amplification (LAMP) assay for the detection of Mur blood group antigen was established., Results: Fifteen of 275 (5·5%) samples were confirmed by LAMP as Mur antigen positive. All the Mur antigen-positive samples were GP.Mur subtype which was confirmed with sequencing., Conclusion: The LAMP method has identical results with conventional serology method but more suitable for large-scale screening., (© 2016 British Blood Transfusion Society.)

Objective: The purpose of this study was to evaluate the predictability of two-dimensional shear wave elastography (2D-SWE) for papillary thyroid microcarcinoma (PTMC)., Materials and Methods: One hundred and eighteen patients with 137 thyroid nodules (46 benign nodules, 91 malignant nodules) were included in this study who received conventional ultrasound (US) and 2D-SWE before fine-needle aspiration or surgery. The diagnostic performance was compared between US findings only and the combined use of US findings with 2D-SWE, which were correlated with pathology results., Results: Receiver-operating characteristic curve analysis was performed to assess the diagnostic performance of 2D-SWE. Conventional US findings and 2D-SWE values were analyzed and compared between benign and malignant thyroid nodules. The mean values of SWE&#95;mean, SWE&#95;min, and SWE&#95;max were 46.6±16.7, 26.2±9.5, and 73.6±18.1 kPa, respectively, in PTMC, which were significantly higher than those in benign tumors (27.8±12.4, 15.8±8.6, and 50.3±22.6 kPa, P<0.001). The optimal cut-off values of SWE&#95;mean, SWE&#95;min, and SWE&#95;max for predicting malignancy were 34.5, 21.8, and 53.2 kPa, respectively. Taller than wide, micro-calcification, and SWE&#95;mean were found to be independent risk factors for predicting PTMC. The overall sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of combined conventional US features with 2D-SWE parameters were 95.7%, 94.5%, 94.9%, 89.8%, and 97.7%, respectively; these were superior to those of conventional US (89.1%, 90.1%, 89.9%, 82.0%, and 93.2%)., Conclusion: The study indicates that the quantitative parameters of 2D-SWE are an independent predictive factor for diagnosing PTMC, which could provide valuable information when conventional US cannot give determinate results.

Norcantharidin (NCTD) has been proven to be able to attenuate renal interstitial fibrosis, but the exact molecular mechanism is still unknown. This study investigated the relationship between the anti-fibrotic effect of NCTD and its inhibition on PP2Ac expression. Here, PP2Ac was found to be positively correlated with extracellular matrix accumulation in the rat unilateral ureteral obstruction (UUO) model. Additional experiments showed that the PP2A inhibitor (okadaic acid) can ameliorate renal interstitial fibrosis by inhibiting the expression of fibronectin (FN) and collagen I (Col-I) and reversing tubular epithelial-to-mesenchymal transition in vivo and in vitro. In vitro experiments also demonstrated that ectopic over-expression of PP2Ac has a profibrotic effect in HK-2 cells. Moreover, NCTD was able to downregulate PP2Ac expression, decrease FN, Col-I, α-SMA expression, and increase E-cadherin expression in a dose-dependent manner both in vivo and in vitro. In particular, it was demonstrated that NCTD induced no evident changes in the expression of FN, Col-I, α-SMA and E-cadherin in HK-2 cells after PP2Ac was knocked down by shRNA. These results indicated that NCTD exerts an anti-fibrosis effect via inhibition of PP2Ac expression. Thus, PP2Ac could be a promising target for intervention in renal interstitial fibrosis.

Real-time polymerase chain reaction (RT-PCR) enables effective and sensitive screening for infectious risk in the field of blood safety. However, when using RT-PCR to detect bacterial contamination, several intractable points must be considered, one of which is the lack of appropriate quality control. In this study, we developed a simplified RT-PCR assay in which the same primer set and two distinct probes were used to detect both, an internal reference control and the target in a reaction. The copy number of the internal reference control represents the positive detection limit of the assay; therefore, when the threshold-cycle value of the target is less than or equal to that of the internal reference control, the result obtained for the target can be considered to be a true positive. When human gDNA was spiked with Escherichia coli gDNA and the detection limit for the internal reference control was set to five copies, the measured detection limit for E. coli gDNA was two copies. The internal reference control duplex RT-PCR assay showed high efficiency (0.91-1.02), high linearity (R2 > 0.99), and good reproducibility in intra- and inter-assay comparisons. Lastly, when human platelet-rich plasma samples were spiked with E. coli or other bacterial species, all species were detected efficiently, and the results of a two-sample pooled t test showed that the limit of detection for E. coli was 1 cfu/mL. Here, we present a synthetic internal reference control molecule and a new statistical method for improving the reliability of RT-PCR assays when screening for bacterial contamination in blood products.

Oxidative stress is an important mechanism of contrast-induced acute kidney injury (CIAKI). The optimal strategy to prevent CIAKI remains unclear. The aim of the present study was to assess the effect of pentoxifylline, a nonspecific phosphodiesterase inhibitor, on the prevention of CIAKI. A total of 32 healthy male Sprague-Dawley rats were randomly divided into normal dietary group (NN; n=8) and a high cholesterol-supplemented dietary group (HN; 4% cholesterol and 1% cholic acid; n=24). At the end of eight weeks, the rats in the high cholesterol diet group were randomly divided into three subgroups (n=8 in each group). CIAKI was induced in two of the subgroups via intravenous injection of the radiocontrast media iohexol (10 ml/kg). Pentoxifylline (50 mg/kg) was administered to one of the iohexol-treated groups via intraperitoneal injection 12 h prior to and following contrast media (CM) injection. Kidney function parameters and oxidative stress markers were then measured. The renal pathological changes were evaluated using hematoxylin and eosin staining and scored semi-quantitatively. In iohexol-injected rats, serum creatinine (Scr), renal pathological scores, renal malondialdehyde (MDA) content, renal NADPH oxidase activity, fractional excretion of sodium (FENa%) and fractional excretion of potassium (FEK%) were significantly increased (P<0.01). The Scr, histologic scores, renal MDA content, NADPH oxidase activity, FENa% and FEK% in the rats treated with pentoxifylline prior to iohexol were observed to be reduced compared with those in rats treated with iohexol alone (P<0.01). This suggests that pentoxifylline significantly attenuates renal injuries, including tubular necrosis and proteinaceous casts induced by CM. It may be concluded that pentoxifylline protected the renal tissue from the nephrotoxicity induced by low-osmolar CM via an antioxidant effect.

Objective: To evaluate the effects of Huai Qi Huang (HQH) granules on primary glomerulonephritis patients, and to discuss its possible mechanisms., Method: Sixteen patients diagnosed with primary glomerular disease between December 2011 and December 2012 were enrolled. Their blood and urine samples were collected at day 0 (the baseline levels), 30, and 90 of receiving HQH granules orally. Levels of creatinine and cystatin C (Cys-C) in serum and urine, and total protein and albumin in urine were measured by automatic biochemical analyzer. Neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine was tested by ELISA; serum malondialdehyde (MDA) was measured by thiobarbituric acid method, the erythrocyte count in urine was calculated under light microscope., Results: Serum levels of creatinine, MDA, Cys-C and NGAL at day 30 and 90 were significantly lower than the baseline levels. Urinary levels of Cys-C, NGAL, total protein, albumin and erythrocyte counts were also decreased; level of estimated glomerular filtration (eGFR) was increased., Conclusion: HQH granules have certain effect on delaying the development of primary glomerular disease with mild proteinuria and hematuresis in patients. This study may supply a new treatment for primary glomerular diseases.

Background/aims: This study was designed to investigate whether urinary kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18) and cystatin C (Cys-C) are early predictive biomarkers for gadolinium-based contrast-induced nephropathy (Gd-CIN) in the elderly patients undergoing gadolinium-enhanced magnetic resonance imaging (MRI)., Methods: 60 elderly patients undergoing enhanced MRI using gadolinium-based contrast media were enrolled. Urine samples were collected before and 24 hours and 48 hours after the procedure, and KIM-1, IL-18 and Cys-C levels were measured by using an ELLSA kit respectively. Serum samples before and 24 hours and 48 hours after the procedure were also collected, and creatinine was measured by automatic biochemical analyzer., Results: Gd-CIN was diagnosed in 8 of 60 (13.3%) patients. At 24 hours after MRI with gadolinium administration in the Gd-CIN group, the urinary KIM-1, IL-18 and Cys-C were significantly increased. Logistic regression analysis showed that urinary KIM-1 and IL-18 at 24 hours after gadolinium injection were independent predictive markers of Gd-CIN. The predictable time of acute kidney injury (AKI) onset determined by urinary KIM-1, IL-18 and Cys-C was 24 hours earlier than by serum creatinine., Conclusions: Urinary KIM-1, IL-18 and Cys-C could be early predictive biomarkers of Gd-CIN in the elderly patients, which showed a good performance in early diagnosis of Gd-CIN as compared with serum creatinine.

Objective: The objective of this study is to evaluate the effect and mechanism of mitochondria-targeted peptides (MTP131 and SPI20) on contrast-induced acute kidney injury (CI-AKI) in rats with hypercholesterolemia., Method: Forty SD rats were randomly divided into normal diet group (NN, n = 8) and high cholesterol supplemented dietary group (HN, n = 32). At the end of 8 weeks, the group HN was divided into four subgroups. All Rats were given injection of either diatrizoate (10 mL/kg) or equal volume of normal saline, the rats pretreated with MTP131 or SPI20 were given injection with MTP131 or SPI 20 (3 mg/kg) by peritoneal cavity for 3 times. Blood, urine and renal tissue samples were prepared to determine biochemical parameters. The renal pathological changes were evaluated by hematoxylin and eosin staining and scored semiquantitatively, The protein expression of renal NOX4 was also measured by Western blotting., Results: In diatrizoate-injected rats, Serum creatinine (Scr), fractional excretion of sodium (FeNa%), fractional excretion of potassium (FeK%), pathological scores, renal malondialdehyde (MDA) content, the NADPH oxidase activity and the expression of NOX4 in kidney tissue were significantly increased (p < 0.01). In the groups pretreated with MTP131 or SPI20, the levels of Scr, FeNa%, FeK%, MDA content and NADPH oxidase activity in renal tissue decreased (p < 0.01), the levels of renal super oxygen dehydrogenises and ATPase activity increased (p < 0.01). The renal injuries induced by contrast media (CM) were alleviated., Conclusion: MTP131 and SPI20 might protect acute kidney injury induced by CM in rats with hypercholesterolemia.

To evaluate the in-flight performance of a new hyperspectral sensor onboard an unmanned aerial vehicle (UAV-HYPER), a comprehensive field campaign was conducted over the Baotou test site in China on 3 September 2011. Several portable reference reflectance targets were deployed across the test site. The radiometric performance of the UAV-HYPER sensor was assessed in terms of signal-to-noise ratio (SNR) and the calibration accuracy. The SNR of the different bands of the UAV-HYPER sensor was estimated to be between approximately 5 and 120 over the homogeneous targets, and the linear response of the apparent reflectance ranged from approximately 0.05 to 0.45. The uniform and non-uniform Lambertian land surface reflectance was retrieved and validated using in situ measurements, with root mean square error (RMSE) of approximately 0.01-0.07 and relative RMSE of approximately 5%-12%. There were small discrepancies between the retrieved uniform and non-uniform Lambertian land surface reflectance over the homogeneous targets and under low aerosol optical depth (AOD) conditions (AOD = 0.18). However, these discrepancies must be taken into account when adjacent pixels had large land surface reflectance contrast and under high AOD conditions (e.g. AOD = 1.0).