Engineering Two-Dimensional Nodal Semimetals in Functionalized Biphenylene by Fluorine Adatoms.

We propose a band engineering scheme on the biphenylene network, a newly synthesized carbon allotrope. We illustrate that the electronic structure of the biphenylene network can be significantly altered by controlling conditions affecting the symmetry and destructive interference of wave functions through periodic fluorination. First, we investigate the mechanism for the appearance of a type-II Dirac fermion in a pristine biphenylene network. We show that the essential ingredients are mirror symmetries and stabilization of the compact localized eigenstates via destructive interference. While the former is used for the band-crossing point along high symmetry lines, the latter induces highly inclined Dirac dispersions. Subsequently, we demonstrate the transformation of the biphenylene network's type-II Dirac semimetal phase into various Dirac phases such as type-I Dirac, gapped type-II Dirac, and nodal line semimetals through the deliberate disruption of mirror symmetry or modulation of destructive interference by varying the concentration of fluorine atoms.

Antibiotic-induced intestinal microbiota depletion can attenuate the acute kidney injury to chronic kidney disease transition via NADPH oxidase 2 and trimethylamine-N-oxide inhibition.

Intestinal microbiota and their metabolites affect systemic inflammation and kidney disease outcomes. Here, we investigated the key metabolites associated with the acute kidney injury (AKI)-to chronic kidney disease (CKD) transition and the effect of antibiotic-induced microbiota depletion (AIMD) on this transition. In 61 patients with AKI, 59 plasma metabolites were assessed to determine the risk of AKI-to-CKD transition. An AKI-to-CKD transition murine model was established four weeks after unilateral ischemia-reperfusion injury (IRI) to determine the effects of AIMD on the gut microbiome, metabolites, and pathological responses related to CKD transition. Human proximal tubular epithelial cells were challenged with CKD transition-related metabolites, and inhibitory effects of NADPH oxidase 2 (NOX2) signals were tested. Based on clinical metabolomics, plasma trimethylamine N-oxide (TMAO) was associated with a significantly increased risk for AKI-to-CKD transition [adjusted odds ratio 4.389 (95% confidence interval 1.106-17.416)]. In vivo, AIMD inhibited a unilateral IRI-induced increase in TMAO, along with a decrease in apoptosis, inflammation, and fibrosis. The expression of NOX2 and oxidative stress decreased after AIMD. In vitro, TMAO induced fibrosis with NOX2 activation and oxidative stress. NOX2 inhibition successfully attenuated apoptosis, inflammation, and fibrosis with suppression of G2/M arrest. NOX2 inhibition (in vivo) showed improvement in pathological changes with a decrease in oxidative stress without changes in TMAO levels. Thus, TMAO is a key metabolite associated with the AKI-to-CKD transition, and NOX2 activation was identified as a key regulator of TMAO-related AKI-to-CKD transition both in vivo and in vitro.

The effect of renal function on the pharmacokinetics and pharmacodynamics of enavogliflozin, a potent and selective sodium-glucose cotransporter-2 inhibitor, in type 2 diabetes.

AIMS: To explore the effect of renal function on the pharmacokinetic (PK) and pharmacodynamic (PD) profile and safety of enavogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: An open-label, two-part clinical trial was conducted in T2DM patients, stratified by renal function: Group 1, normal renal function; Group 2, mild renal impairment (RI); Group 3, moderate RI; and Group 4, severe RI. In Part A, Groups 2 and 4 received enavogliflozin 0.5 mg once. In Part B, Groups 1 and 3 received enavogliflozin 0.5 mg once daily for 7 days. Serial blood and timed urine samples were collected to analyse the PK and PD characteristics of enavogliflozin. Pearson's correlation coefficients were calculated to assess the correlations between PK or PD parameters and creatinine clearance (CrCL). RESULTS: A total of 21 patients completed the study as planned. The area under the curve (AUC) for enavogliflozin was not significantly correlated with CrCL, although the maximum concentration slightly decreased as renal function decreased. By contrast, daily urinary glucose excretion (UGE) was positively correlated with CrCL after both single- (r = 0.7866, p < 0.0001) and multiple-dose administration (r = 0.6606, p = 0.0438). CONCLUSIONS: Systemic exposure to oral enavogliflozin 0.5 mg was similar among the patients with T2DM regardless of their renal function levels. However, the glucosuric effect of enavogliflozin decreased with RI. Considering the UGE observed and approved therapeutic use of other SGLT2 inhibitors, the efficacy of enavogliflozin with regard to glycaemic control could be explored in patients with mild and moderate RI (estimated glomerular filtration rate ≥30 or ≥45 mL/min/1.73 m2) in a subsequent larger study.

Long-term ozone exposure and mortality in patients with chronic kidney disease: a large cohort study.

BACKGROUND: Epidemiologic studies on the effects of long-term exposure to ozone (O3) have shown inconclusive results. It is unclear whether to O3 has an effect on chronic kidney disease (CKD). We investigated the effects of O3 on mortality and renal outcome in CKD. METHODS: We included 61,073 participants and applied Cox proportional hazards models to examine the effects of ozone on the risk of end-stage renal disease (ESRD) and mortality in a two-pollutants model adjusted for socioeconomic status. We calculated the concentration of ozone exposure one year before enrollment and used inverse distance weighting (IDW) for interpolation, where the exposure was evenly distributed. RESULTS: In the single pollutant model, O3 was significantly associated with an increased risk of ESRD and all-cause mortality. Based on the O3 concentration from IDW interpolation, this moving O3 average was significantly associated with an increased risk of ESRD and all-cause mortality. In a two-pollutants model, even after we adjusted for other measured pollutants, nitrogen dioxide did not attenuate the result for O3. The hazard ratio (HR) value for the district-level assessment is 1.025 with a 95% confidence interval (CI) of 1.014-1.035, while for the point-level assessment, the HR value is 1.04 with a 95% CI of 1.035-1.045. The impact of ozone on ESRD, hazard ratio (HR) values are, 1.049(95%CI: 1.044-1.054) at the district unit and 1.04 (95%CI: 1.031-1.05) at the individual address of the exposure assessment. The ozone hazard ratio for all-cause mortality was 1.012 (95% confidence interval: 1.008-1.017) for administrative districts and 1.04 (95% confidence interval: 1.031-1.05) for individual addresses. CONCLUSIONS: This study suggests that long-term ambient O3 increases the risk of ESRD and mortality in CKD. The strategy to decrease O3 emissions will substantially benefit health and the environment.

Air quality and kidney health: Assessing the effects of PM10, PM2.5, CO, and NO2 on renal function in primary glomerulonephritis.

BACKGROUND: While extensive studies have elucidated the relationships between exposure to air pollution and chronic diseases, such as cardiovascular disorders and diabetes, the intricate effects on specific kidney diseases, notably primary glomerulonephritis (GN)-an immune-mediated kidney ailment-are less well understood. Considering the escalating incidence of GN and conspicuous lack of investigative focus on its association with air quality, investigation is dedicated to examining the long-term effects of air pollutants on renal function in individuals diagnosed with primary GN. METHODS: This retrospective cohort analysis was conducted on 1394 primary GN patients who were diagnosed at Seoul National University Bundang Hospital and Seoul National University Hospital. Utilizing time-varying Cox regression and linear mixed models (LMM), we examined the effect of yearly average air pollution levels on renal function deterioration (RFD) and change in estimated glomerular filtration rate (eGFR). In this context, RFD is defined as sustained eGFR of less than 60 mL/min per 1.73 m2. RESULTS: During a mean observation period of 5.1 years, 350 participants developed RFD. Significantly, elevated interquartile range (IQR) levels of air pollutants-including PM10 (particles ≤10 micrometers, HR 1.389, 95 % CI 1.2-1.606), PM2.5 (particles ≤2.5 micrometers, HR 1.353, 95 % CI 1.162-1.575), CO (carbon monoxide, HR 1.264, 95 % CI 1.102-1.451), and NO2 (nitrogen dioxide, HR 1.179, 95 % CI 1.021-1.361)-were significantly associated with an increased risk of RFD, after factoring in demographic and health variables. Moreover, exposure to PM10 and PM2.5 was associated with decreased eGFR. CONCLUSIONS: This study demonstrates a substantial link between air pollution exposure and renal function impairment in primary GN, accentuating the significance of environmental determinants in the pathology of immune-mediated kidney diseases.

Characterizing Glomerular Barrier Dysfunction with Patient-Derived Serum in Glomerulus-on-a-Chip Models: Unveiling New Insights into Glomerulonephritis.

Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy.

Plasma Circulating Tumor Necrosis Factor Receptors at Multiple Time Points Can Predict the Outcome of Severe Acute Kidney Injury.

INTRODUCTION: This prospective cohort study investigated the clinical role of circulating tumor necrosis factor receptor (cTNFR) levels as prognostic biomarkers in severe acute kidney injury (AKI) patients requiring continuous renal replacement therapy (CRRT). METHODS: We enrolled 136 patients from 7 hospitals participating in the VENUS (VolumE maNagement Under body composition monitoring in critically ill patientS on CRRT) trial from July 2017 to October 2019. The levels of cTNFR1 and cTNFR2 were measured using plasma samples collected on days 0 (D0), 2 (D2), and 7 (D7). Patients were divided into high- and low-cTNFR groups based on their receptor concentrations. RESULTS: D0 concentrations of cTNFR1 and cTNFR2 were positively correlated with one another (R2 = 0.37, p < 0.001). The high-cTNFR1 group displayed a higher in-hospital mortality rate than the low-TNFR1 group (p = 0.002). Moreover, the mortality rate was significantly higher in the high-TNFR1 group than in the low-TNFR1 group after adjusting for age, sex, and acute physiology, and chronic health evaluation II scores (hazard ratio 1.82, 95% confidence interval 1.09-3.03, p = 0.025). D2 and D7 cTNFR1 levels were also associated with in-hospital mortality; contrastingly, cTNFR2 levels were not associated with this outcome. Additionally, patients were divided into three groups according to the change in cTNFR levels from D0 to D2 (ΔcTNFR). Those in the highest ΔcTNFR tertile had a higher mortality rate than the remaining patients (p = 0.033 for ΔcTNFR1; p = 0.025 for ΔcTNFR2). Patients who underwent AKI-to-chronic kidney disease transition had higher concentrations of cTNFR1 (p = 0.014). DISCUSSION/CONCLUSION: Plasma cTNFR1 concentrations at CRRT initiation and changes in cTNFR1 and 2 levels immediately following CRRT initiation are significant biomarkers for predicting the outcomes of patients with severe AKI.

Magnetic Ordering, Anomalous Lifshitz Transition, and Topological Grain Boundaries in Two-Dimensional Biphenylene Network.

We study the electronic properties of a new planar carbon crystal formed through networking biphenylene molecules. Novel electronic features among carbon materials such as zone-center saddle point and peculiar type-II Dirac fermionic states are shown to exist in the low-energy electronic spectrum. The type-II state here has a nearly flat branch and is close to a transition to type I. Possible magnetic instabilities related to low-energy bands are discussed. Furthermore, with a moderate uniaxial strain, a pair of Dirac points merge with the zone-center saddle point, realizing concurrent Lifshitz transitions of van Hove singularity as well as pair annihilation of the Dirac fermions. A new effective Hamiltonian encompassing all distinctive low-energy states is constructed, revealing a finite winding number of the pseudospin texture around the Dirac point, quantized Zak phases, and topological grain boundary states.

Efficacy of Mesenchymal-Stromal-Cell-Derived Extracellular Vesicles in Ameliorating Cisplatin Nephrotoxicity, as Modeled Using Three-Dimensional, Gravity-Driven, Two-Layer Tubule-on-a-Chip (3D-MOTIVE Chip).

Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) are known to have a therapeutic effect on nephrotoxicity. As animal models require significant time and resources to evaluate drug effects, there is a need for a new experimental technique that can accurately predict drug effects in humans. We evaluated the therapeutic effect of MSC-derived EVs in cisplatin nephrotoxicity using a three-dimensional, gravity-driven, two-layer tubule-on-a-chip (3D-MOTIVE chip). In the 3D-MOTIVE chip, 10 µM cisplatin decreased the number of attached cells compared to the vehicle. Conversely, annexin V and reactive oxygen species (ROS) were increased. Cell viability was increased 2.8-fold and 2.5-fold after treatment with EVs at 4 and 8 µg/mL, respectively, compared to the cisplatin-induced nephrotoxicity group. Cell attachment was increased 2.25-fold by treatment with 4 µg/mL EVs and 2.02-fold by 8 µg/mL EVs. Annexin V and ROS levels were decreased compared to those in the cisplatin-induced nephrotoxicity group. There were no significant differences in annexin V and ROS levels according to EV concentration. In sum, we created a cisplatin-induced nephrotoxicity model on a 3D-MOTIVE chip and found that MSC-derived EVs could restore cell viability. Thus, MSC-derived EVs may have the potential to ameliorate cisplatin-induced nephrotoxicity.

Fatal Systemic Capillary Leak Syndrome after SARS-CoV-2Vaccination in Patient with Multiple Myeloma.

A young man with smoldering multiple myeloma died of hypotensive shock 2.5 days after severe acute respiratory syndrome coronavirus 2 vaccination. Clinical findings suggested systemic capillary leak syndrome (SCLS); the patient had experienced a previous suspected flare episode. History of SCLS may indicate higher risk for SCLS after receiving this vaccine.

Target value of mean arterial pressure in patients undergoing continuous renal replacement therapy due to acute kidney injury.

BACKGROUND: Although patients undergoing continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI) frequently have instability in mean arterial pressure (MAP), no consensus exists on the target value of MAP related to high mortality after CRRT. METHODS: A total of 2,292 patients who underwent CRRT due to AKI in three referral hospitals were retrospectively reviewed. The MAPs were divided into tertiles, and the 3rd tertile group served as a reference in the analyses. The major outcome was all-cause mortality during the intensive care unit period. The odds ratio (OR) of mortality was calculated using logistic regression after adjustment for multiple covariates. The nonlinear relationship regression model was applied to determine the threshold value of MAP related to increasing mortality. RESULTS: The mean value of MAP was 80.7 ± 17.3 mmHg at the time of CRRT initiation. The median intensive care unit stay was 5 days (interquartile range, 2-12 days), and during this time, 1,227 (55.5%) patients died. The 1st tertile group of MAP showed an elevated risk of mortality compared with the 3rd tertile group (adjusted OR, 1.28 [1.03-1.60]; P = 0.029). In the nonlinear regression analysis, the threshold value of MAP was calculated as 82.7 mmHg. Patients with MAP < 82.7 mmHg had a higher mortality rate than those with ≥ 82.7 mmHg (adjusted OR, 1.21 [1.01-1.45]; P = 0.037). CONCLUSIONS: Low MAP at CRRT initiation is associated with a high risk of mortality, particularly when it is < 82.7 mmHg. This value may be used for risk classification and as a potential therapeutic target.

Real-Time Clinical Decision Support Based on Recurrent Neural Networks for In-Hospital Acute Kidney Injury: External Validation and Model Interpretation.

BACKGROUND: Acute kidney injury (AKI) is commonly encountered in clinical practice and is associated with poor patient outcomes and increased health care costs. Despite it posing significant challenges for clinicians, effective measures for AKI prediction and prevention are lacking. Previously published AKI prediction models mostly have a simple design without external validation. Furthermore, little is known about the process of linking model output and clinical decisions due to the black-box nature of neural network models. OBJECTIVE: We aimed to present an externally validated recurrent neural network (RNN)-based continuous prediction model for in-hospital AKI and show applicable model interpretations in relation to clinical decision support. METHODS: Study populations were all patients aged 18 years or older who were hospitalized for more than 48 hours between 2013 and 2017 in 2 tertiary hospitals in Korea (Seoul National University Bundang Hospital and Seoul National University Hospital). All demographic data, laboratory values, vital signs, and clinical conditions of patients were obtained from electronic health records of each hospital. We developed 2-stage hierarchical prediction models (model 1 and model 2) using RNN algorithms. The outcome variable for model 1 was the occurrence of AKI within 7 days from the present. Model 2 predicted the future trajectory of creatinine values up to 72 hours. The performance of each developed model was evaluated using the internal and external validation data sets. For the explainability of our models, different model-agnostic interpretation methods were used, including Shapley Additive Explanations, partial dependence plots, individual conditional expectation, and accumulated local effects plots. RESULTS: We included 69,081 patients in the training, 7675 in the internal validation, and 72,352 in the external validation cohorts for model development after excluding cases with missing data and those with an estimated glomerular filtration rate less than 15 mL/min/1.73 m2 or end-stage kidney disease. Model 1 predicted any AKI development with an area under the receiver operating characteristic curve (AUC) of 0.88 (internal validation) and 0.84 (external validation), and stage 2 or higher AKI development with an AUC of 0.93 (internal validation) and 0.90 (external validation). Model 2 predicted the future creatinine values within 3 days with mean-squared errors of 0.04-0.09 for patients with higher risks of AKI and 0.03-0.08 for those with lower risks. Based on the developed models, we showed AKI probability according to feature values in total patients and each individual with partial dependence, accumulated local effects, and individual conditional expectation plots. We also estimated the effects of feature modifications such as nephrotoxic drug discontinuation on future creatinine levels. CONCLUSIONS: We developed and externally validated a continuous AKI prediction model using RNN algorithms. Our model could provide real-time assessment of future AKI occurrences and individualized risk factors for AKI in general inpatient cohorts; thus, we suggest approaches to support clinical decisions based on prediction models for in-hospital AKI.

Role of Human Primary Renal Fibroblast in TGF-ß1-Mediated Fibrosis-Mimicking Devices.

Renal fibrosis is a progressive chronic kidney disease that ultimately leads to end-stage renal failure. Despite several approaches to combat renal fibrosis, an experimental model to evaluate currently available drugs is not ideal. We developed fibrosis-mimicking models using three-dimensional (3D) co-culture devices designed with three separate layers of tubule interstitium, namely, epithelial, fibroblastic, and endothelial layers. We introduced human renal proximal tubular epithelial cells (HK-2), human umbilical-vein endothelial cells, and patient-derived renal fibroblasts, and evaluated the effects of transforming growth factor-ß (TGF-ß) and TGF-ß inhibitor treatment on this renal fibrosis model. The expression of the fibrosis marker alpha smooth muscle actin upon TGF-ß1 treatment was augmented in monolayer-cultured HK-2 cells in a 3D disease model. In the vascular compartment of renal fibrosis models, the density of vessels was increased and decreased in the TGF-ß-treated group and TGF-ß-inhibitor treatment group, respectively. Multiplex ELISA using supernatants in the TGF-ß-stimulating 3D models showed that pro-inflammatory cytokine and growth factor levels including interleukin-1 beta, tumor necrosis factor alpha, basic fibroblast growth factor, and TGF-ß1, TGF-ß2, and TGF-ß3 were increased, which mimicked the fibrotic microenvironments of human kidneys. This study may enable the construction of a human renal fibrosis-mimicking device model beyond traditional culture experiments.

Cancer development and mortality differences in patients with glomerulonephritis after renal biopsy: a single center retrospective cohort study.

BACKGROUND: The association between glomerulonephritis (GN) and cancer has been well known for decades. However, studies evaluating long-term de novo cancer development in patients with GN are limited. This study aimed to evaluate the incidence of cancer development among patients with renal biopsy-proven GN during post-biopsy follow-up and the differences in outcomes according to cancer occurrence. METHODS: We conducted a retrospective cohort study of adult patients who underwent renal biopsy at Seoul National Bundang Hospital between 2003 and 2017. After excluding 778 patients with age < 18 years, cancer diagnosis before or within 6 months after renal biopsy, immunosuppressant therapy before renal biopsy, or pathologic diagnoses other than GN, 822 patients were included in the analysis. Data on baseline clinical characteristics, renal biopsy results, and types and doses of immunosuppressant agents were collected from electronic medical records. The incidence of cancer was censored on the date when the first cancer was diagnosed. We evaluated rates of mortality and end-stage renal disease (ESRD) development during follow-up. RESULTS: During a mean follow-up period of 58.9 ± 44.5 months, 45 subjects (5.5%) developed de novo cancer. A comparison of clinical characteristics between subjects who did and did not develop cancer revealed that cancer patients were older and had higher comorbidities and immunosuppressant use. Overall, patients with GN had an elevated standardized incidence ratio (SIR) of 7.16 (95% confidence interval (CI): 5.22-9.61) relative to the age- and sex-matched general population. In particular, the SIR was significantly higher in GNs such as membranous nephropathy (MN), IgA nephropathy, lupus nephritis, and focal segmental glomerulosclerosis. Multivariable Cox proportional hazard model revealed that patients with MN had an increased risk of cancer development, with a hazard ratio of 2.30 [95% CI: 1.06-4.98]. Patients with MN who developed cancer had a significantly higher risk of mortality (hazard ratio: 6.59; 95% CI: 1.22-35.56, P = 0.03) than those without cancer, but there was a non-significant difference in ESRD development. CONCLUSIONS: Patients with GN without concurrent cancer, particularly those with MN, have significantly higher risks of cancer development and subsequent mortality and should remain aware of the potential development of malignancy during follow-up.

Simple Postoperative AKI Risk (SPARK) Classification before Noncardiac Surgery: A Prediction Index Development Study with External Validation.

BACKGROUND: Researchers have suggested models to predict the risk of postoperative AKI (PO-AKI), but an externally validated risk index that can be practically implemented before patients undergo noncardiac surgery is needed. METHODS: We performed a retrospective observational study of patients without preexisting renal failure who underwent a noncardiac operation (≥1 hour) at two tertiary hospitals in Korea. We fitted a proportional odds model for an ordinal outcome consisting of three categories: critical AKI (defined as Kidney Disease Improving Global Outcomes AKI stage ≥2, post-AKI death, or dialysis within 90 days after surgery), low-stage AKI (defined as PO-AKI events not fulfilling the definition of critical AKI), and no PO-AKI. RESULTS: The study included 51,041 patients in a discovery cohort and 39,764 patients in a validation cohort. The Simple Postoperative AKI Risk (SPARK) index included a summation of the integer scores of the following variables: age, sex, expected surgery duration, emergency operation, diabetes mellitus, use of renin-angiotensin-aldosterone inhibitors, baseline eGFR, dipstick albuminuria hypoalbuminemia, anemia, and hyponatremia. The model calibration plot showed tolerable distribution of observed and predicted probabilities in both cohorts. The discrimination power of the SPARK index was acceptable in both the discovery (c-statistic 0.80) and validation (c-statistic 0.72) cohorts. When four SPARK classes were defined on the basis of the sum of the risk scores, the SPARK index and classes fairly reflected the risks of PO-AKI and critical AKI. CONCLUSIONS: Clinicians may consider implementing the SPARK index and classifications to stratify patients' PO-AKI risks before performing noncardiac surgery.

Hyperuricemia is associated with acute kidney injury and all-cause mortality in hospitalized patients.

AIM: Hyperuricemia is a risk factor for high morbidity and mortality in several diseases. However, the relationship between uric acid (UA) and the risk of acute kidney injury (AKI) and mortality remain unresolved in hospitalized patients. METHODS: Data from 18 444 hospitalized patients were retrospectively reviewed. The odds ratio (OR) for AKI and the hazard ratio (HR) for all-cause mortality were calculated based on the UA quartiles after adjustment for multiple variables. All analyses were performed after stratification by sex. RESULTS: The fourth quartile group (male, UA > 6.7 mg/dL; female, UA > 5.4 mg/dL) showed a higher risk of AKI compared with the first quartile group (male, UA < 4.5 mg/dL; female, UA < 3.6 mg/dL), with the following OR: 3.2 (2.55-4.10) in males (P < 0.001); and 3.1 (2.40-4.19) in females (P < 0.001). There were more patients who did not recover from AKI in the fourth quartile compared with the first quartile, with the following OR: 2.0 (1.32-3.04) in males (P = 0.001) and 2.4 (1.43-3.96) in females (P = 0.001). The fourth quartile group had a higher risk of all-cause mortality compared with the first quartile group, with the following HR: 1.4 (1.20-1.58) in males (P < 0.001) and 1.2 (1.03-1.46) in females (P = 0.019). The in-hospital mortality risk was also higher in the fourth quartile compared with the first quartile, which was significant only in males (OR, 2.1 (1.33-3.31) (P = 0.002)). CONCLUSION: Hyperuricemia increases the risks of AKI and all-cause mortality in hospitalized patients.

Development of a new mortality scoring system for acute kidney injury with continuous renal replacement therapy.

AIM: On the basis of the worst outcomes of patients undergoing continuous renal replacement therapy (CRRT) in intensive care unit, previously developed mortality prediction model, Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) needs to be modified. METHODS: A total of 828 patients who underwent CRRT were recruited. Mortality prediction model was developed for the prediction of death within 7 days after starting the CRRT. Based on regression analysis, modified scores were assigned to each variable which were originally used in the APACHE II and SOFA scoring models. Additionally, a new abbreviated Mortality Scoring system for AKI with CRRT (MOSAIC) was developed after stepwise selection analysis. RESULTS: We used all the variables included in the APACHE II and SOFA scoring models. The prediction powers indicated by C-statistics were 0.686 and 0.683 for 7-day mortality by the APACHE II and SOFA systems, respectively. After modification of these models, the prediction powers increased up to 0.752 for the APACHE II and 0.724 for the SOFA systems. Using multivariate analysis, seven significant variables were selected in the MOSAIC model wherein its C-statistic value was 0.772. These models also showed good performance with 0.720, 0.734 and 0.773 of C-statistics in the modified APACHE II, modified SOFA and MOSAIC scoring models in the external validation cohort (n = 497). CONCLUSION: The modified APACHE II/SOFA and newly developed MOSAIC models could be more useful tool for predicting mortality for patients receiving CRRT.

Hyperphosphatemia and risks of acute kidney injury, end-stage renal disease, and mortality in hospitalized patients.

BACKGROUND: Hyperphosphatemia is associated with vascular calcification and bone mineral disorders and is a major concern among patients with chronic kidney disease (CKD). However, the relationship between hyperphosphatemia and renal outcome in non-CKD patients has not been studied. Furthermore, the clinical implications of hyperphosphatemia in relation to the risks of acute kidney injury (AKI), end-stage renal disease (ESRD), and mortality after hospitalization remain unresolved. METHODS: A total of 20,686 patients (aged ≥18 years) admitted to Seoul National University Bundang Hospital from January 2013 to December 2013 were retrospectively reviewed. Patients were divided into quartiles according to serum phosphorus level at the time of admission. The odds ratios (ORs) for AKI and hazard ratios (HRs) for ESRD and all-cause mortality were calculated after adjustment of multiple covariates. RESULTS: AKI developed in 2319 patients (11.2%), with higher ORs for patients in the third and fourth quartiles (1.4 [1.24-1.68] and 2.8 [2.44-3.22], respectively) compared with the first quartile group. During a median follow-up period of 4.0 years, 183 patients (0.88%) developed ESRD and 3675 patients (17.8%) died. Patients in the fourth quartile had higher risks of ESRD and mortality than patients in the first quartile (HRs, 2.3 [1.46-3.75] and 1.4 [1.22-1.49], respectively). These trends remained consistent in patients with an estimated glomerular filtration rate > 60 ml/min/1.73 m2. CONCLUSIONS: Hyperphosphatemia is related to the risks of AKI, ESRD, and mortality, and it may therefore be necessary to monitor serum phosphorus level in hospitalized patients, irrespective of kidney function.

Impact of Electronic Acute Kidney Injury (AKI) Alerts With Automated Nephrologist Consultation on Detection and Severity of AKI: A Quality Improvement Study.

BACKGROUND: Several electronic alert systems for acute kidney injury (AKI) have been introduced. However, their clinical benefits require further investigation. STUDY DESIGN: Before-and-after quality improvement study. SETTING & PARTICIPANTS: A tertiary teaching hospital in Korea, which adopted an AKI alert system on June 1, 2014. Before and after launch of the alert system, 1,884 and 1,309 patients with AKI were included in the usual-care and alert groups, respectively. QUALITY IMPROVEMENT PLAN: Implementation of an AKI alert system through which clinicians could generate automated consultations to the nephrology division for all hospitalized patients. OUTCOMES: Primary outcomes included overlooked AKI events, defined as not measuring the follow-up creatinine value, and the consultation pattern of clinicians. Secondary outcomes were severe AKI events; AKI recovery, defined based on the creatinine-based criterion; and patient mortality. MEASUREMENTS: ORs for events of overlooked AKI, early consultation, and severe AKI were calculated with logistic regression. AKI recovery rate and patient mortality were assessed using Cox regression. RESULTS: After introduction of the alert system, the odds of overlooked AKI events were significantly lower (adjusted OR, 0.40; 95% CI, 0.30-0.52), and the odds of an early consultation with a nephrologist were greater (adjusted OR, 6.13; 95% CI, 4.80-7.82). The odds of a severe AKI event was reduced after implementation of the alerts (adjusted OR, 0.75; 95% CI, 0.64-0.89). Furthermore, the likelihood of AKI recovery was improved in the alert group (adjusted HR, 1.70; 95% CI, 1.53-1.88). Mortality was not affected by the AKI alert system (adjusted HR, 1.07; 95% CI, 0.68-1.68). LIMITATIONS: Possible unreported differences between the alert and usual-care groups. CONCLUSIONS: Implementation of the AKI alert system was associated with beneficial effects in terms of an improved rate of recovery from AKI. Therefore, widespread adoption of such systems could be considered in general hospitals.

Permissive fluid volume in adult patients undergoing extracorporeal membrane oxygenation treatment.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a cardiorespiratory support technique for patients with circulatory or pulmonary failure. Frequently, large-volume fluid resuscitation is needed to ensure sufficient extracorporeal blood flow in patients initiating ECMO. However, excessive overhydration is known to increase mortality in critically ill patients. Therefore, in order to define a tolerant volume range in patients undergoing ECMO treatment, the association between cumulative fluid balance (CFB) and outcome was evaluated in patients undergoing ECMO. METHODS: This retrospective multicenter cohort study was conducted with 723 patients who underwent ECMO in three tertiary care hospitals between 2005 and 2016. CFB was calculated as total fluid input minus total fluid output during the first 3 days from ECMO initiation. The patients were divided into groups that initiated ECMO owing to cardiovascular disease (CVD)-related or non-cardiovascular disease (non-CVD)-related causes. The primary endpoint was mortality within 90 days after ECMO commencement. RESULTS: Totals of 406 and 317 patients were included in the CVD and non-CVD groups, respectively. In the CVD group, the mean age was 58.4 ± 17.7 years, and 68.2% were male. The mean age was 55.7 ± 15.7 years, and 65.3% were male in the non-CVD group. The median CFB values were 64.7 and 53.5 ml/kg in the CVD and non-CVD groups, respectively. Multivariable analysis using Cox proportional hazards models revealed a significantly increased risk of 90-day mortality in patients with higher CFB values in both the CVD and non-CVD groups. However, the risks were elevated only in the two CFB quartile groups with the largest CFB amounts. Cubic spline models showed that mortality risk began to increase significantly when CFB was 82.3 ml/kg in the CVD group. In patients with respiratory diseases, the mortality risk increase was significant for those with CFB levels above 189.6 ml/kg. CONCLUSIONS: Mortality risk did not increase until a certain level of fluid overload was reached in patients undergoing ECMO. Adequate fluid resuscitation is critical to improving outcomes in these patients.