New Criterion to Evaluate Acute-on-Chronic Kidney Injury Based on the Creatinine Reference Change.

BACKGROUND: The lack of consensus criteria of acute on chronic kidney injury (ACKI) affects the judgment for its clinical prognosis. METHODS: In this study, we analyzed the data from 711,615 hospitalized adults who had at least 2 serum creatinine (SCr) tests within 30 days. We estimated the reference change value (RCV) of SCr given initial SCr level in adults without known risks of acute kidney injury other than chronic kidney disease (CKD). We proposed a criterion for ACKI based on the RCV of SCr (cROCK), which defined ACKI as a ≥25% increase in SCr in 7 days. We validated cROCK by its association with the risks of in-hospital mortality, death after discharge, and CKD progression in a large cohort of patients with CKD stage 3. RESULTS: In 21,661 patients with CKD stage 3, a total of 3,145 (14.5%), 1,512 (7.0%), and 221 (1.0%) ACKI events were detected by both cROCK and Kidney Disease Improving Global Outcomes (KDIGO), cROCK only, and KDIGO only, respectively. cROCK detected 40% more ACKI events than KDIGO. Compared with patients without ACKI by both definitions, those with cROCK- but not KDIGO-defined ACKI had a significantly increased risk of in-hospital mortality (hazard ratio [HR] 5.53; 95% CI 3.75-8.16), death after discharge (HR 1.51; 95% CI 1.21-1.83), and CKD progression (OR 5.65; 95% CI 3.05-10.48). CONCLUSIONS: RCV-based criterion (cROCK) for ACKI is clinically valid in that it has a substantially improved sensitivity in identifying patients with high risk of adverse outcomes.

IPDN-China promotes the development of pediatric dialysis in China.

BACKGROUND: In mainland China, dialysis for children with end-stage renal disease (ESRD) was not introduced until the 1980s. To describe the development of pediatric dialysis in different regions of China, a national pediatric dialysis network, namely, International Pediatric Dialysis Network-China (IPDN-China) ( www.pedpd.org.cn ), was launched in 2012. METHODS: Original and updated information from the renal centers registered with the IPDN-China was collected between 2012 and 2016 from two sources, namely, the registry and the survey, and demographic features were analyzed. RESULTS: Due to promotion by the IPDN-China, the number of registered renal centers increased from 12 to 39 between 2012 and 2016, with a significant increase in the coverage of the Chinese administrative divisions (from 26.5 to 67.6%) (p < 0.01); and the coverage of the pediatric (0~14 years old) population increased to nearly 90% in 2016. The distribution of renal centers indicated that East China had the highest average number of registered centers per million population (pmp) 0~14-year-old age group. Seventeen relatively large dialysis centers were distributed across 14 divisions. Various modalities of renal replacement therapy (RRT) were available in most centers. The IPDN-China has promoted collaborations between dieticians, psychologists, and social workers on dialysis teams to provide better service to children with ESRD and their families. The proportion of centers with all three types of paramedic support (i.e., dieticians, psychologists, and social workers) as well as the proportion of centers with a partial paramedic team significantly increased between 2012 (25.0%) and 2016 (69.2%) (p < 0.05). In terms of the point prevalent cases of patients (aged < 18 years), data from the survey of 39 registered centers revealed that the number of children with ESRD who were on RRT was 578 (49% received a kidney transplant) at the end of 2016, which was more than that reported in previous surveys. Data from the registry showed that 349 dialysis patients had been enrolled as of the end of 2016. The median age at RRT start was 9.5 years, and the leading cause of ESRD was congenital abnormalities of the kidney and urinary tract (CAKUT). CONCLUSIONS: The IPDN-China has helped to promote the development of pediatric dialysis for ESRD in China by improving the organization of care for dialysis patients and increasing the availability and the quality of RRT for patients who need it. To improve knowledge about the epidemiology and outcomes of pediatric RRT around the country, a sustained effort needs to be made by the IPDN-China to increase the enrollment of dialysis patients and increase the number of registered centers in the future.

Noninvasive evaluation of renal oxygenation in children with chronic kidney disease using blood-oxygen-level-dependent magnetic resonance imaging.

BACKGROUND: Renal hypoxia is considered a final pathway in the progression of chronic kidney disease (CKD). Blood-oxygen-level-dependent magnetic resonance imaging (BOLD-MRI) has shown merit for evaluating renal oxygenation in adults. OBJECTIVE: To investigate renal cortical and medullary R2* values by CKD stage and by renal function index in children with chronic kidney disease. MATERIALS AND METHODS: Twenty-one children with CKD Stage 1-3, 16 children with CKD Stage 4-5, and 6 healthy volunteers underwent a renal MRI using multigradient recalled-echo sequence with 16 echoes. We measured the R2* values of the renal cortex and medulla on BOLD-MRI. RESULTS: The cortical R2* value was ranked as CKD Stage 4-5 > CKD Stage 1-3 > healthy controls, and the medullary R2* value was ranked as CKD Stage 4-5 > CKD Stage 1-3. There was no significant difference in the medullary R2* value between CKD Stage 1-3 patients and the healthy controls. There was a positive correlation between the R2* values in the renal cortex (r=0.73) and medulla (r=0.89), and the serum creatinine level (P<0.001), and the renal cortical and medullary R2* values were negatively correlated with the estimated glomerular filtration rate (r=-0.71 and r=-0.89, respectively; P<0.001). CONCLUSION: BOLD-MRI might contribute to noninvasive assessment of renal oxygenation in children with CKD in vivo but it did not reflect renal function in our sample.

[Risk Factors for Sepsis Associated-Acute Kidney Injury in Intensive Care Unit Patients].

OBJECTIVE: To explore the risk factors of acute kidney injury (AKI) in patients with sepsis in intensive care unit (ICU). METHODS: The medical records of patients diagnosed with sepsis in ICU of West China Hospital of Sichuan University from March 2009 to June 2016 were retrospectively analyzed. Differences between AKI group and Non-AKI group in general data, background disease, ICU entry and exit dates, complications, laboratory data and other related data were analyzed through univariate and multivariate statistical methods. RESULTS: A total of 2331 patients with sepsis were included in the study, including 626 patients in the AKI group and 1695 patients in the Non-AKI group. The multivariate logistic regression analysis revealed that age >40 yr. (odds ratio (OR) =2.752), diabetes (OR=2.563), hypertension/coronary heart disease (OR=1.851), chronic kidney disease (OR=15.876), heart failure (OR=2.295), acute respiratory distress syndrome (OR=2.067), severe acute pancreatitis (OR=2.725), hypotension (OR=2.140), hypoproteinemia (OR=1.596), lactic acidosis (OR=2.164), organ failure>1 (OR=4.480), WBC>10×10 9L -1 (OR=4.166), serum creatinine (OR=4.401), PCT (OR=1.816), Cys-C (OR=7.046), mild anemia (OR=2.107), moderate anemia (OR=3.817), and severe anemia (OR=6.091) were all independent risk factors of SA-AKI. CONCLUSION: Several risk factors are related to the occurrence of SA-AKI in the ICU. Early identification and monitoring of risk factors for SA-AKI and early prevention of AKI can improve the prognosis of sepsis patients.

A New Criterion for Pediatric AKI Based on the Reference Change Value of Serum Creatinine.

BACKGROUND: Current definitions of AKI do not take into account serum creatinine's high variability in children. METHODS: We analyzed data from 156,075 hospitalized children with at least two creatinine tests within 30 days. We estimated reference change value (RCV) of creatinine on the basis of age and initial creatinine level in children without kidney disease or known AKI risk, and we used these data to develop a model for detecting pediatric AKI on the basis of RCV of creatinine. We defined pediatric AKI according to pediatric reference change value optimized for AKI in children (pROCK) as creatinine increase beyond RCV of creatinine, which was estimated as the greater of 20 µmol/L or 30% of the initial creatinine level. RESULTS: Of 102,817 children with at least two serum creatinine tests within 7 days, 5432 (5.3%) had AKI as defined by pROCK compared with 15,647 (15.2%) and 10,446 (10.2%) as defined by pediatric RIFLE (pRIFLE) and Kidney Disease Improving Global Outcomes (KDIGO), respectively. Children with pROCK-defined AKI had significantly increased risk of death (hazard ratio, 3.56; 95% confidence interval, 3.15 to 4.04) compared with those without AKI. About 66% of patients with pRIFLE-defined AKI and 51% of patients with KDIGO-defined AKI, mostly children with initial creatinine level of <30 µmol/L, were reclassified as non-AKI by pROCK, and mortality risk in these children was comparable with risk in those without AKI by all definitions. CONCLUSIONS: pROCK criterion improves detection of "true" AKI in children compared with earlier definitions that may lead to pediatric AKI overdiagnosis.

Nephronophthisis: A review of genotype-phenotype correlation.

Nephronophthisis is an autosomal recessive cystic kidney disease and one of the most common genetic disorders causing end-stage renal disease in children. Nephronophthisis is a genetically heterogenous disorder with more than 25 identified genes. In 10%-20% of cases, there are additional features of a ciliopathy syndrome, such as retinal defects, liver fibrosis, skeletal abnormalities, and brain developmental disorders. This review provides an update of the recent advances in the clinical features and related gene mutations of nephronophthisis, and novel approaches for therapy in nephronophthisis patients may be needed.

A review of case and case series reports on Henöch-Schönlein syndrome-related pancreatitis.

To summarize the experience of diagnosing and treating patients with Henoch-Schönlein purpura (HSP)-related pancreatitis, a systematic review of previously published cases was conducted. Among 13 reported cases, there were six males and seven females whose age from 3 to 70 years. The clinical features of these patients indicated that acute pancreatitis could be the initial manifestation of HSP, the radiological change was atypical, and most cases were alleviated with steroidal treatment. Good outcomes can be achieved in patients who are diagnosed early with HSP-related pancreatitis, and it is vital to begin timely treatment of HSP-related pancreatitis with corticosteroid.

[Expression of heparanase in kidney of rats with respiratory syncytial virus nephropathy and its relationship with proteinurina].

OBJECTIVE: To explore the role of heparanase in the pathogenesis of respiratory syncytial virus (RSV) nephropathy in rats model. METHODS: Twenty 150-200 g Sprague-Dawley (SD) rats (n = 5 per group) were inoculated with 6 x 10(6) PFU RSV and sacrificed on days 4, 8, 14 and 28 postinoculation (RSV4, RSV8, RSV14 and RSV29). Five SD rats inoculated with Dulbecco's minimum essential medium were served as normal control. The expression levels of heparanase protein and mRNA in the rat renal tissue of each group were determined by immunohistochemical staining and real-time quantitative RT-PCR respectively. The proteinurina was also measured and then the relationship between the expression level of heparanase and the 24-hour urinary protein was studied. RESULTS: The rats with RSV nephropathy exhibited higher proteinuria in comparison with normal rats, and the 24-hour urinary protein level was significantly different between each RSV nephropathy group (RSV14 > RSV8 > RSV28 > RSV4, P < 0.05). Compared with normal control, the rats with RSV nephropathy showed up-regulated expression of heparanase protein in glomeruli. The expression levels of heparanase protein in RSV8 and RSV14 group were higher than those in RSV4 and RSV28 group (P < 0.05). There was a linear positive correlation between the expression level of glomerular heparanase protein and the quantity of 24-hour urinary protein (r = 0.783, P < 0.05). Compared with normal control group, the expression levels of heparanase mRNA in the kidney from RSV4, RSV8, RSV14, and RSV28 group were elevated (RSV14 > RSV8 > RSV4 > RSV28 , P < 0.05). There was a linear positive correlation between the expression level of renal heparanase mRNA and the quantity of 24-hour urinary protein (r = 0.725, P < 0.05). CONCLUSION: The increased expression of heparanase in kidney may be important to the loss of glomerular negative charge in glomerular basement membrane which is involved in the pathogenesis of RSV nephropathy in rats.

[Primary culture and identification of rat glomerular podocytes].

OBJECTIVE: To establish an easy and feasible method for primary culture and identification of rat glomerular podocytes. METHODS: Glomeruli from Sprague-Dawley (SD) rats weighing 60-100 gram were isolated by the method of different size combination of screen. Isolated glomeruli were appropriately digested with 2 g/L type IV collagenase and cultured in 25 cm2 plastic flask coated with rat tail collagen in K1-3T3 medium with ITS-X (containing insulin-transferrin-selenium). Subculture of primary cultured epithelial cells was performed at 9-10 days after implantation of collagenase digested glomeruli. Podocytes were identified by the morphology study with scanning electron microscope and inverted microscope, as well as the immunohistochemistry staining (SP methods) study for the expression of keratin, desmin and Wilms' tumor suppressor-1 (WT-1). RESULTS: Epithelial cells outgrowth from isolated glomeruli appeared after 3 days primary culture and grew to confluence with cobblestone-appearance at 9-10 days. These cobblestone cells were subcultured at this point and gradually conversed into large, flat arborized cells with well-developed processes and microvilli. These arborized cells were negative expression with desmin staining and showed positive expression of cytokeratin and WT-1, which indicated that they were podocytes. CONCLUSION: Implantating collagenase digested-glomeruli is an easy and feasible method for primary culture of rat glomerular podocytes. WT-1 may serve as a good marker to identify rat glomerular podocytes.

[Mechanical ventilation in acute respiratory distress syndrome].

The goal of mechanically ventilating patients with acute respiratory distress syndrome (ARDS) is to ensure adequate oxygenation and minimal ventilator-associated lung injury. Non-invasive ventilation should be cautiously used in patients with ARDS. Protective ARDS mechanical ventilation strategies with low tidal volumes can reduce mortality. Driving pressure is the most reasonable parameter to optimize tidal volume. Available evidence does not support the routine use of higher positive end expiratory pressure (PEEP) in patients with ARDS. The optimal level of PEEP may be titrated by the inflection point obtained from static pressure-volume curve. Promising therapies include prone position ventilation, high frequency oscillatory ventilation and extracorporeal membrane oxygenation as salvage treatment. While mechanically ventilating, it is also important for ARDS patients to maintain spontaneous breathing via assisted ventilation mode such as bilevel positive airway pressure, pressure support ventilation and neurally adjusted ventilation assist. Exogenous surfactant, inhaled nitric oxide, bronchodilators, airway pressure release ventilation and partial liquid ventilation are not recommended therapies.

[Mechanism for promoting repair of renal ischemia reperfusion injury by mesenchymal stem cells].

OBJECTIVE: Preclinical studies have demonstrated that exogenous mesenchymal stem cells (MSCs) may ameliorate kidney damage and enhance repair of renal ischemia reperfusion injury (IRI). This review will focus on the mechanism for accelerating repair of renal IRI by MSCs. Several chemokine receptors such as CXCR4 and CD44 are related to MSCs trafficking to post-ischemic kidney. MSCs differentiate into tubular epithelial cells, which is not the predominant mechanism for repair of the damaged kidney. Instead, MSCs exert their therapeutic effect mainly through paracrine action via a variety of cytokines and microvesicles, and the paracrine actions of infused MSCs work to activate intrinsic kidney cells, promote angiogenesis, inhibit oxidative stress and reduce apoptosis, inflammation and renal fibrosis.

Clinical significance of IgM and C3 deposition in children with primary immunoglobulin A nephropathy.

BACKGROUND: Mesangial IgM and C3 deposition is commonly observed in patients with primary immunoglobulin A nephropathy (IgAN), but its characteristics and prognosis have rarely been reported. The aim of this study was to investigate the relationship between combined mesangial IgM and C3 deposition and disease progression in children with IgAN. METHODS: One hundred sixteen children diagnosed with IgAN between 2016 and 2020 were selected. Renal biopsies were scored by Oxford classification including the presence of mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis and crescents. The primary renal outcome was an event of either ≥ 50% reduction of eGFR from the baseline value or the onset of end-stage renal disease within the follow-up period. Cox regression analysis was performed to examine the effect of the combined mesangial IgM and C3 deposition on renal outcomes. RESULTS: Forty-seven (40.52%) patients presented combined mesangial IgM and C3 deposition. Compared with children without combined IgM and C3 deposition, children with combined IgM and C3 deposition presented higher mesangial hypercellularity, endocapillary hypercellularity and cresentic lesions in kidney biopsies, and higher prevalence of renal dysfunction (19.15% versus 2.90%; P = 0.007). Renal outcome was also significantly worse as revealed by Kaplan-Meier curves (P = 0.0034). Multivariable Cox analysis identified tubular atrophy/interstitial fibrosis lesions [hazard ratio (HR) 14.843, 95% CI, 3.497-62.997, P < 0.001] and intensity of IgM deposition (HR 2.838, 95% CI, 1.321-6.094, P = 0.007) as independent risk factors for poor renal function. CONCLUSIONS: Combined mesangial IgM and C3 deposition was associated with unfavorable histopathological features. Mesangial IgM deposition was an independent risk factor for poor renal outcomes in children with primary IgAN.

Gal-9/Tim-3 signaling pathway activation suppresses the generation of Th17 cells and promotes the induction of Foxp3+ regulatory T cells in renal ischemia-reperfusion injury.

CD4+ T cells mediate the pathogenesis of renal ischemia-reperfusion injury (IRI). Emerging research suggests that a Th17/regulatory T cell (Treg) imbalance plays a pivotal role in the development of renal IRI. A recently identified negative checkpoint protein, T cell immunoglobulin domain and mucin domain family 3 (Tim-3), inhibits the immune response by binding to its ligand, galectin-9 (Gal-9). However, the role of the Gal-9/Tim-3 signaling pathway in the regulation of CD4+ T cell subsets in renal IRI remains unclear. In this study, we investigated the effect of the Gal-9/Tim-3 signaling pathway on Th17/Treg subsets in renal IRI using a mouse model. Renal IRI induced the expression of Gal-9 in renal tubular epithelial cells and increased the proportion of Tim-3+ Th17 cells and Tim-3+ forkhead box P3 (Foxp3)+ Treg cells in the ischemia-reperfusion (IR) kidneys. Administration of rAAV9-Gal-9 suppressed kidney inflammation, reduced the mortality of mice with renal IRI, increased Foxp3+ Treg cells, and reduced Th17 cells. In contrast, the blockade of Tim-3 in vivo using an anti-Tim-3 monoclonal antibody aggravated renal inflammation, decreased Foxp3+ Treg cells, and promoted Th17 cells. Thus, Gal-9/Tim-3 signaling pathway activation may protect against renal IRI by inhibiting Th17 cell production and inducing Foxp3+ Treg cell expansion. Our study suggests that the Gal-9/Tim-3 signaling pathway may be targeted by immunotherapy in renal IRI.

Idiopathic membranous nephropathy in children: A case report.

BACKGROUND: Minimal change disease is a common cause of nephrotic syndrome (NS) in children and has a good prognosis. Idiopathic membranous nephropathy (IMN), a rare cause of NS in children, may progress to chronic kidney disease. However, there is little data on how to evaluate and treat IMN in children. CASE SUMMARY: In this article, we report the case of a 7-year-old boy with steroid-resistant NS. After cyclophosphamide pulse therapy combined with oral prednisone, the urinary protein results remained positive. Renal biopsy confirmed the pathological diagnosis of stage II MN, with positivity for phospholipase A2 receptor. Other immunological and infectious diseases relevant to secondary MN were ruled out by laboratory tests. Subsequently, tacrolimus plus prednisone was administered, and the therapeutic effect was satisfactory. CONCLUSION: IMN is rare in children. The main clinical manifestation is NS. The diagnosis depends on renal biopsy. There is little evidence-based data on the treatment of IMN in children. Therefore, large-sample randomized controlled trials need to be performed. Individualized treatment should be used to improve the prognosis of the disease.

Risk factors and optimal predictive scoring system of mortality for children with acute paraquat poisoning.

BACKGROUND: There is no suitable scoring system that can be used to predict mortality in children with acute paraquat intoxication (APP). AIM: To optimize a predictive scoring system for mortality in children with APP. METHODS: A total of 113 children with APP from January 1, 2010 to January 1, 2020 were enrolled in this study. These patients were divided into survivors and non-survivors. We compared the clinical characteristics between the two groups and analyzed the independent prognostic risk factors. The survival rates of patients with different values of the pediatric critical illness score (PCIS) were assessed using kaplan-meier survival analysis. The best scoring system was established by using the area under the receiver operating characteristic curve analysis. RESULTS: The overall mortality rate was 23.4%. All non-survivors died within 20 days; 48.1% (13/27) died within 3 days, and 70.3% (19/27) died within 7 days. Compared to survivors, the non-survivors were older, had higher white blood cell count, alanine aminotransferase (ALT), aspartate aminotransferase, serum creatinine, blood urea nitrogen, glucose, and pediatric early warning score, and had lower platelet count, albumin, Serum sodium (Na+) and PCIS. ALT and PCIS were the independent prognostic risk factors for children with APP. The survival rate of children classified as extremely critical patients (100%) was lower than that of children classified as critical (60%) or noncritical (6.7%) patients. The specificity of ALT was high (96.51%), but the sensitivity was low (59.26%). The sensitivity and specificity of ALT combined with PCIS were high, 92.59% and 87.21%, respectively. The difference in mortality was significantly higher for ALT combined with PCIS (area under the receiver operating characteristic: 0.937; 95%CI: 0.875-0.974; P < 0.05). CONCLUSION: In our study, ALT and PCIS were independent prognostic risk factors for children with APP. ALT combined with PCIS is an optimal predictive mortality scoring system for children with APP.

Psychological research of the children with chronic kidney disease and their guardians during the COVID-19 pandemic.

Background: There is great mental stress due to the coronavirus disease 2019 (COVID-19) pandemic. However, there are no detailed psychological studies of the children with chronic kidney disease (CKD) and their guardians during the COVID-19 pandemic. Objective: This study explores the psychological pressure on children with CKD and their guardians. Methods: An online survey was conducted at 20 of the largest pediatric nephropathy departments in China, including the Rutter Parent Questionnaire, Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). Overall, 885 children (589 children with CKD associated with 296 children of the control group) completed the survey together with their guardians. Results: There was no statistical difference between CKD children and control children regarding their Rutter behavior scores and abnormal behaviors. Nevertheless, the abnormal behavior of children might aggravate the anxiety and depression of guardians in both CKD and control groups (p < 0.05). We confirmed that the anxiety and depression of guardians in the CKD group were both significantly higher than those in the control group (p < 0.05). The guardians in the CKD group with lower annual income were more likely to experience anxiety (p < 0.05). Furthermore, the guardians whose children were older than 11 years old might be more anxious than those who were 6-11 years old. Besides, the guardians in the CKD group who watched the news for 30-60 min daily were less likely to have depression than those who watched < 10 min (p < 0.05). The subgroup results showed that the gender, the time of watching the news, the annual income of guardians, and children's age might be the most critical factors influencing guardians' psychological burden. Conclusion: The guardians in the CKD group have more severe anxiety and depression during the pandemic. The children's abnormal behavior, adolescents' pressure, low household income, and the panic about the pandemic may be the main reasons for the anxiety and depression of guardians.

Efficacy and Safety of Vadadustat for Anemia in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Background: Vadadustat is a novel drug for treating anemia patients with chronic kidney disease (CKD), but its effect and safety remain uncertain. This study aimed to summarize the evidence for vadadustat in the treatment of CKD patients with anemia. Methods: PubMed, Ovid Medline, Embase, Cochrane CENTRAL, Wanfang Data, China National Knowledge Infrastructure and an international trial register were searched from their inception to June 2021 for randomized controlled trials (RCTs) comparing the efficacy and safety of vadadustat to those of placebo or erythropoiesis-stimulating agents (ESAs) in treating anemia in CKD patients. Data were pooled in a meta-analysis, with results expressed as the mean difference for continuous outcomes and relative risk for categorical outcomes with 95% confidence intervals (95% CIs). The certainty of evidence was rated according to Cochrane methods and the GRADE approach. Results: Ten RCTs comparing vadadustat with placebo (4 RCTs) or darbepoetin alfa (6 RCTs) were included (n = 8,438 participants). Compared with placebo, vadadustat increased the hemoglobin (Hb) response rate (risk ratio 5.27; 95% CI: 2.69 to 10.31; p < 0.001; high certainty of evidence) and Hb level from baseline (∆Hb) (mean difference (MD) 1.28; 95% CI: 0.83 to 1.73; p < 0.001; low certainty of evidence). Compared with placebo or darbepoetin alfa, vadadustat decreased hepcidin (MD -36.62; 95% CI: -54.95 to -18.30; p < 0.001) and ferritin (MD -56.24; 95% CI: -77.37 to -35.11; p < 0.001) levels and increased iron-binding capacity (MD 24.38; 95% CI: 13.69 to 35.07; p < 0.001), with a low to moderate certainty of evidence. Moderate to high certainty evidence suggested that compared with placebo or darbepoetin alfa, vadadustat significantly increased the risk of nausea and diarrhea but did not significantly increase the risk of serious adverse events, especially all-cause mortality, cardiac events and nonfatal stroke. Conclusion: Vadadustat may safely improve Hb levels and promote iron utilization in CKD patients with anemia without increasing the incidence of serious adverse events.

Application of Delphi method and analytic hierarchy process to establish indicator system for evaluation of rational drug use in children with primary nephrotic syndrome: Observational study.

Nephrotic syndrome (NS) can be divided into primary, secondary, and congenital NS 3 types, and primary nephrotic syndrome (PNS) accounts for about 90% of the total number of NS in children, which is a common childhood glomerular disease one. The treatment of children with PNS has been controversial and confused because of hormone tolerance, complications, multiple drug combinations, and other issues, but there are no indicators to assess the rational drug use (RDU) of children with PNS. This study aims to develop a set of indicators to assess the RDU in children with PNS.The study is an observational study and the procedure includes 3 steps:A consensus was reached after 2 rounds of the Delphi survey and each indicator was weighted. The final indicators included 2 first-rank indicators and 16 second-rank indicators. In round 1, modified 3 indicators, increase 2 indicators and delete 6 indicators. In round 2, reached consensus. The first-rank indicators comprised drug choice (46.96%) and drug usage and dosage (53.04%); The second-rank indicators aimed to the specific drug therapy, including the RDU of hormones, immunomodulators, and adjuvant drug. The score of each indicator met the requirements, therefore, childrens PNS RDU evaluation index system had been established and the index was scientific and credible.The first set indicators had been established to assess RDU of children with PNS. Monitoring these indicators will guide people towards the promotion of RDU for PNS. Whats more, the indicator provided a methodological reference for the development of other indicator sets.

Long noncoding RNA TANCR promotes γδ T cells activation by regulating TRAIL expression in cis.

BACKGROUND: γδ T cells are an important subset of T lymphocytes that play important roles in innate and adaptive immunity via the secretion of various cytokines. Previous studies have found that long noncoding RNAs (lncRNAs) are critical regulators that contribute to the development of immune cells. However, the functions of lncRNAs in the γδ T cells remains poorly studied. RESULTS: Here, we identified the novel function of lncRNA NONHSAT196558.1 in isopentenyl pyrophosphate (IPP)-activated and -expanded γδ T cells using RNA-seq. As it functioned as an activating noncoding RNA of tumor necrosis factor related apoptosis-inducing ligand (TRAIL), an important cytotoxic cytokine that expressed by γδ T cells in responding to various infectious agents, we named this lncRNA as TANCR. Secondly, the expression of TANCR was found to be positively correlated with TRAIL expression in IPP activated γδ T cells. In addition, TANCR was confirmed to localized both in nucleus and cytoplasm. Finally, a loss-of-function was conducted by using siRNA/ASO or CRISPR/Cas9 system to knockdown or knockout TANCR, and confirmed that silencing of TANCR inhibits TRAIL expression in several kinds of cells, including HEK293T cells, Jurkat cells, and primary γδ T cells. CONCLUSION: These evidences demonstrate that TANCR play important roles in γδ T cell activation. Furthermore, TANCR may be involved in the cytotoxicity of γδ T cells. This study aims to further our understanding of the molecular mechanisms underlying lncRNA-mediated immune responses.

Proton pump inhibitors and the risk of hospital-acquired acute kidney injury in children.

BACKGROUND: To evaluate the association between use of proton pump inhibitor (PPI) and the risk of hospital-acquired acute kidney injury (HA-AKI) in hospitalized children. METHODS: We conducted a multicenter retrospective cohort study in hospitalized children aged 1 month to 18 years from 25 tertiary hospitals across China from 2013 to 2015. Patient-level data were obtained from the electronic hospitalization databases. AKI was defined and staged using the serum creatinine (SCr) data according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: Among 42,232 children analyzed, 11,496 (27.2%) used PPI, 1,760 (4.2%) used histamine 2 receptor antagonist (H2RA), and 3,514 (8.3%) had HA-AKI during hospitalization. Over 85% of PPIs were prescribed for prophylaxis of gastro-duodenal lesions in children. The use of PPI was associated with a significantly increased risk of HA-AKI compared with both non-users [odds ratio (OR), 1.37; 95% confidence interval (CI), 1.23-1.53)] and H2RA users (OR, 1.24; 95% CI, 1.01-1.52). The associations were consistent across children of different age range, gender, subtypes of PPIs and methods of administration. A larger effect was observed in children with chronic kidney disease (OR, 3.37; 95% CI, 2.46-4.62) and those needed intensive care (OR, 1.54; 95% CI, 1.33-1.78). The risk of HA-AKI was increased even within the recommended dosage range of PPI. CONCLUSIONS: PPIs were widely used and associated with an increased risk of HA-AKI in hospitalized children in China.