Intrahepatic IgA complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of HCC.

BACKGROUND AND AIMS: Cancer-associated fibroblasts (CAFs) play key roles in the tumor microenvironment. IgA contributes to inflammation and dismantling antitumor immunity in the human liver. In this study, we aimed to elucidate the effects of the IgA complex on CAFs in Pil Soo Sung the tumor microenvironment of HCC. APPROACH AND RESULTS: CAF dynamics in HCC tumor microenvironment were analyzed through single-cell RNA sequencing of HCC samples. CAFs isolated from 50 HCC samples were treated with mock or serum-derived IgA dimers in vitro. Progression-free survival of patients with advanced HCC treated with atezolizumab and bevacizumab was significantly longer in those with low serum IgA levels ( p <0.05). Single-cell analysis showed that subcluster proportions in the CAF-fibroblast activation protein-α matrix were significantly increased in patients with high serum IgA levels. Flow cytometry revealed a significant increase in the mean fluorescence intensity of fibroblast activation protein in the CD68 + cells from patients with high serum IgA levels ( p <0.001). We confirmed CD71 (IgA receptor) expression in CAFs, and IgA-treated CAFs exhibited higher programmed death-ligand 1 expression levels than those in mock-treated CAFs ( p <0.05). Coculture with CAFs attenuated the cytotoxic function of activated CD8 + T cells. Interestingly, activated CD8 + T cells cocultured with IgA-treated CAFs exhibited increased programmed death-1 expression levels than those cocultured with mock-treated CAFs ( p <0.05). CONCLUSIONS: Intrahepatic IgA induced polarization of HCC-CAFs into more malignant matrix phenotypes and attenuates cytotoxic T-cell function. Our study highlighted their potential roles in tumor progression and immune suppression.

Expansion of effector regulatory T cells in steroid responders of severe alcohol-associated hepatitis.

While steroid therapy is the preferred treatment for severe alcohol-associated hepatitis, the role of effector regulatory T (eTreg) cells and their association with steroid response and clinical outcomes in these patients remains to be elucidated. We prospectively enrolled 47 consecutive patients with alcohol-associated hepatitis, consisting of severe alcohol-associated hepatitis treated with steroids (n=18; steroid-treated group) and mild alcohol-associated hepatitis (n=29; nontreated group). After isolating peripheral blood mononuclear cells from the patients at enrollment and again 7 days later, the frequency of eTreg cells was examined using flow cytometry. Single-cell RNA sequencing analysis was conducted using paired peripheral blood mononuclear cells. In vitro experiments were also performed to assess phenotype changes and the suppressive function of Treg cells following steroid treatment. The steroid-treated group exhibited significantly higher Model for End-Stage Liver Disease scores than the nontreated group (p < 0.01). Within the steroid-treated group, the proportion of eTreg cells significantly expanded in the steroid responders (n=13; p = 0.01). Furthermore, a significant positive correlation was observed between the decrease in the Model for End-Stage Liver Disease score and the increase in eTreg cells (p < 0.05). Single-cell RNA sequencing using paired peripheral blood mononuclear cells (pre-steroid and post-steroid therapy) from a steroid responder revealed gene expression changes in T cells and monocytes, suggesting enhancement of Treg cell function. In vitro results showed an elevation in the proportion of eTreg cells after steroid therapy. In conclusion, our findings suggest that the efficacy of steroid therapy in patients with severe alcohol-associated hepatitis is mediated by an increase in the number of eTreg cells.

Hyperlactatemia is a predictor of mortality in patients undergoing continuous renal replacement therapy for acute kidney injury.

BACKGROUND: Hyperlactatemia occurs frequently in critically ill patients, and this pathologic condition leads to worse outcomes in several disease subsets. Herein, we addressed whether hyperlactatemia is associated with the risk of mortality in patients undergoing continuous renal replacement therapy (CRRT) due to acute kidney injury. METHODS: A total of 1,661 patients who underwent CRRT for severe acute kidney injury were retrospectively reviewed between 2010 and 2020. The patients were categorized according to their serum lactate levels, such as high (≥ 7.6 mmol/l), moderate (2.1-7.5 mmol/l) and low (≤ 2 mmol/l), at the time of CRRT initiation. The hazard ratios (HRs) for the risk of in-hospital mortality were calculated with adjustment of multiple variables. The increase in the area under the receiver operating characteristic curve (AUROC) for the mortality risk was evaluated after adding serum lactate levels to the Sequential Organ Failure Assessment (SOFA) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score-based models. RESULTS: A total of 802 (48.3%) and 542 (32.6%) patients had moderate and high lactate levels, respectively. The moderate and high lactate groups had a higher risk of mortality than the low lactate group, with HRs of 1.64 (1.22-2.20) and 4.18 (2.99-5.85), respectively. The lactate-enhanced models had higher AUROCs than the models without lactates (0.764 vs. 0.702 for SOFA score; 0.737 vs. 0.678 for APACHE II score). CONCLUSIONS: Hyperlactatemia is associated with mortality outcomes in patients undergoing CRRT for acute kidney injury. Serum lactate levels may need to be monitored in this patient subset.

Analyzing the contribution of gully erosion to land degradation in the upper Blue Nile basin, Ethiopia.

Soil erosion has become a worldwide problem that threatens the environment and the future of economic and social development. The purpose of this study is to investigate the contribution of steep slopes and gullies to erosion in high precipitation tropical areas of the Ethiopian highlands. A trapezoidal weir was installed at the head and tail of the gully to monitor the discharge and sediment concentration from 2017 to 2020. Sediment yield and runoff are heavily influenced by the amount and timing of precipitation. The coefficients of variation for total sediment loads ranged from 65.1 to 96.1% at the head and 17.1-78.1% at the tail; the lowest coefficients were found in 2018 and the highest in 2020. Furthermore, 85% of the sediment at the tail comes from the gully, according to the four-year sediment budget. Further, a hysteretic analysis of suspended sediment concentration and runoff revealed that hilly sediment sources are limited (clockwise), then sediment can be transported through the gully via bank failures (counterclockwise). Study findings contributed to a classification of runoff patterns and an investigation of suspended sediment dynamics. In the gully tail, sediment yield was higher than in the head, suggesting gully sediment contributed more to sediment yield than large upland catchments. As a result of the study, we have been able to develop practical recommendations for managing gully erosion in the future.

Causal effects of physical activity or sedentary behaviors on kidney function: an integrated population-scale observational analysis and Mendelian randomization study.

BACKGROUND: An investigation into the causality of the effects of physical activity and specific sedentary activities on kidney function in the general population is warranted. METHODS: In this observational cohort study, first, the clinical associations of the prevalence of stages 3-5 chronic kidney disease (CKD) and the estimated glomerular filtration rate (eGFR) with physical activity, determined by self-report or objective wrist-band accelerometer results, and sedentary activities (watching television, using a computer and driving) were investigated in 329 758 UK Biobank participants. To assess causality, a two-sample Mendelian randomization (MR) analysis was performed to investigate the associations of a genetic predisposition to physical activity and a sedentary lifestyle with the risk of kidney function impairment in an independent CKDGen genome-wide association study (N = 567 460). The findings were replicated with the 321 024 UK White British Biobank participants in the allele-score-based one-sample MR. RESULTS: A higher degree of self-reported or accelerometer-determined moderate-to-vigorous physical activity was associated with a higher eGFR, while a longer time spent watching television was significantly associated with a lower eGFR and a higher prevalence of CKD. The two-sample MR demonstrated that the genetic predisposition to a higher degree of physical activity was associated with a lower risk of CKD and a higher eGFR, while the genetically predicted television watching duration was associated with a higher risk of CKD and a lower eGFR. The other sedentary behaviors yielded inconsistent results. The findings were similarly replicated in the one-sample MR. CONCLUSION: Physical activity and television watching causally affect kidney function in the general population.

Longitudinal trajectory of acidosis and mortality in acute kidney injury requiring continuous renal replacement therapy.

BACKGROUND: Acidosis frequently occurs in severe acute kidney injury (AKI), and continuous renal replacement therapy (CRRT) can control this pathologic condition. Nevertheless, acidosis may be aggravated; thus, monitoring is essential after starting CRRT. Herein, we addressed the longitudinal trajectory of acidosis on CRRT and its relationship with worse outcomes. METHODS: The latent growth mixture model was applied to classify the trajectories of pH during the first 24 hours and those of C-reactive protein (CRP) after 24 hours on CRRT due to AKI (n = 1815). Cox proportional hazard models were used to calculate hazard ratios of all-cause mortality after adjusting multiple variables or matching their propensity scores. RESULTS: The patients could be classified into 5 clusters, including the normally maintained groups (1st cluster, pH = 7.4; and 2nd cluster, pH = 7.3), recovering group (3rd cluster with pH values from 7.2 to 7.3), aggravating group (4th cluster with pH values from 7.3 to 7.2), and ill-being group (5th cluster, pH < 7.2). The pH clusters had different trends of C-reactive protein (CRP) after 24 hours; the 1st and 2nd pH clusters had lower levels, but the 3rd to 5th pH clusters had an increasing trend of CRP. The 1st pH cluster had the best survival rates, and the 3rd to 5th pH clusters had the worst survival rates. This survival difference was significant despite adjusting for other variables or matching propensity scores. CONCLUSIONS: Initial trajectories of acidosis determine subsequent worse outcomes, such as mortality and inflammation, in patients undergoing CRRT due to AKI.

Causal Effects of Positive Affect, Life Satisfaction, Depressive Symptoms, and Neuroticism on Kidney Function: A Mendelian Randomization Study.

BACKGROUND: Further investigation of the causal effects of psychologic wellbeing on kidney function is warranted. METHODS: In this Mendelian randomization (MR) study, genetic instruments for positive affect, life satisfaction, depressive symptoms, and neuroticism were introduced from a previous genome-wide association study meta-analysis of European individuals. Summary-level MR was performed using the CKDGen data of European ancestry (n=567,460), and additional allele score-based MR was performed in the individual-level data of White British UK Biobank participants (n=321,024). RESULTS: In summary-level MR with the CKDGen data, depressive symptoms were a significant causative factor for kidney function impairment (CKD OR, 1.45; 95% confidence interval, 1.07 to 1.96; eGFR change [%] beta -2.18; 95% confidence interval, -3.61 to -0.72) and pleiotropy-robust sensitivity analysis results supported the causal estimates. A genetic predisposition for positive affect was significantly associated with better kidney function (CKD OR, 0.69; 95% confidence interval, 0.52 to 0.91), eGFR change [%] beta 1.50; 95% confidence interval, 0.09 to 2.93) and sensitivity MR analysis results supported the finding for CKD outcome, but was nonsignificant for eGFR. Life satisfaction and neuroticism exposures showed nonsignificant causal estimates. In the UK Biobank with covariate-adjusted allele score MR analysis, allele scores for positive affect and life satisfaction were causally associated with reduced risk of CKD and higher eGFR. In contrast, neuroticism allele score was associated with increased risk of CKD and lower eGFR, and depressive symptoms allele score was associated with lower eGFR, but showed nonsignificant association with CKD. CONCLUSIONS: Health care providers in the nephrology field should be aware of the causal linkage between psychologic wellbeing and kidney function.

Atrial fibrillation and kidney function: a bidirectional Mendelian randomization study.

AIMS: The aim of this study was to investigate the causal effects between atrial fibrillation (AF) and kidney function. METHODS AND RESULTS: We performed a bidirectional summary-level Mendelian randomization (MR) analysis implementing the results from a large-scale genome-wide association study for estimated glomerular filtration rate (eGFR) by the CKDGen (N = 765 348) and AF (N = 588 190) to identify genetic instruments. The inverse variance weighted method was the main MR method used. For replication, an allele score-based MR was performed by individual-level data within a UK Biobank cohort of white British ancestry individuals (N = 337 138). A genetic predisposition to AF was significantly associated with decreased eGFR [for log-eGFR, beta -0.003 (standard error, 0.0005), P < 0.001] and increased risk of chronic kidney disease [beta 0.059 (0.0126), P < 0.001]. The significance remained in MR sensitivity analyses and the causal estimates were consistent when we limited the analysis to individuals of European ancestry. Genetically predicted eGFR did not show a significant association with the risk of AF [beta -0.366 (0.275), P = 0.183]. The results were similar in allele score-based MR, as allele score for AF was significantly associated with reduced eGFR [for continuous eGFR, beta -0.079 (0.021), P < 0.001], but allele score for eGFR did not show a significant association with risk of AF [beta -0.005 (0.008), P = 0.530]. CONCLUSIONS: Our study supports that AF is a causal risk factor for kidney function impairment. However, an effect of kidney function on AF was not identified in this study.

Genotype-Phenotype Association in ABCC2 Exon 18 Missense Mutation Leading to Dubin-Johnson Syndrome: A Case Report.

We report a case of a patient with Dubin-Johnson syndrome confirmed by a genetic study. A 50-year-old woman who had symptoms of intermittent right upper quadrant abdominal pain was diagnosed with calculous cholecystitis at another institute and was presented to our hospital for a cholecystectomy. She had no history of liver disease, and her physical examination was normal. Abdominal computed tomography showed a gallbladder stone with chronic cholecystitis. During a laparoscopic cholecystectomy for cholecystitis, a smooth, black-colored liver was noted, and a liver biopsy was performed. The biopsy specimen showed coarse, dark brown granules in centrilobular hepatocytes via hematoxylin and eosin staining. We performed a genetic study using the blood samples of the patient. In the adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2) mutation study, a missense mutation in exon 18 was noted. Based on the black-colored liver without nodularity, conjugated hyperbilirubinemia, the liver biopsy results of the coarse pigment in centrilobular hepatocytes, and the ABCC2 mutation, Dubin-Johnson syndrome was diagnosed. The patient was managed with conservative care using hepatotonics. One month after follow-up, total bilirubin and direct bilirubin remained in a similar range. Another follow-up was planned a month later, and the patient maintained her use of hepatotonics.

Effect of exclosure on subsurface water level and sediment yield in the tropical highlands of Ethiopia.

Grazing is a major cause of soil erosion and land degradation across many parts of Ethiopia. This study examined the effects of exclosure on subsurface water levels, soil erosion, and the relationship between daily rainfall and subsurface water levels. Piezometers were used to measure subsurface water levels in the exclosure area during 2017-2020. We found that sediment yield, runoff, and the volume of subsurface water vary greatly depending on the exclosure and temporal practices used. Exclosure of grazing land was the most effective sustainable land management practice in reducing runoff and sediment yield. In 2019 and 2020, the subsurface water level continued to rise at piezometers with exclosure, which shows that exclosure contributed to the subsurface water level rising. In addition, piezometers in grazing land and the exclosure indicate that runoff trapped by acacia decurrens trees can contribute to significant differences in subsurface water levels. Higher runoff coefficients were observed in 2017 and 2018 than in 2019 and 2020, indicating that the exclosure greatly affects runoff; therefore, its implementation is vital to reduce runoff and enhance water conservation. Sediment yields measured for 2017, 2018, 2019, and 2020 were 140.45, 133.15, 101.03, and 74.39 g L-1 day-1, respectively. In 2017 and 2018, sediment yield increased, while in 2019 and 2020 sediment yield decreased because of an exclosure around the gully's cross-section and communal grazing. This study shows that erosion is reduced by exclosure, possibly due to the restoration of protective vegetation cover. This study revealed that a minimum of human and livestock intervention during the study period considerably increased groundwater levels and decreased soil erosion. Generally, the results of this study indicated that exclosure has a considerable impact on runoff and sediment. Therefore, exclosure implementation is vital to reduce runoff and sediment and enhance water conservation, thus supporting the development of effective communal grazing land management measures on the study sites and other similar environmental settings.

Observational or Genetically Predicted Higher Vegetable Intake and Kidney Function Impairment: An Integrated Population-Scale Cross-Sectional Analysis and Mendelian Randomization Study.

BACKGROUND: Further exploration of the possible effects of vegetable intake on kidney function is warranted. OBJECTIVE: We aimed to study the causality of the association between vegetable intake and kidney function by implementing Mendelian randomization (MR) analysis. METHODS: This study comprised a cross-sectional dietary investigation using UK Biobank data and MR analysis. For the cross-sectional investigation, 432,732 participants aged 40-69 y from the UK Biobank cohort were included. Self-reported vegetable intake was the exposure, and the outcomes were the estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD). Next, we included 337,138 participants of white British ancestry in the UK Biobank, and a genome-wide association study (GWAS) was performed to generate a genetic instrument. For MR, we first performed polygenic score (PGS)-based 1-sample MR. In addition, 2-sample MR was performed with CKDGen GWAS for kidney function traits, and the inverse variance weighted method was the main MR method. RESULTS: Higher vegetable intake was cross-sectionally associated with a higher eGFR (per heaped tablespoon increase; ß: 0.154; 95% CI: 0.144, 0.165) and lower odds of CKD (OR: 0.975; 95% CI: 0.968, 0.982). A PGS for vegetable intake was significantly associated with a higher eGFR [per ordinal category increase (0, 1-3, 4-6, ≥7 tablespoons per day); ß: 4.435; 95% CI: 2.337, 6.533], but the association with CKD remained nonsignificant (OR: 0.468; 95% CI: 0.143, 1.535). In the 2-sample MR, the causal estimates indicated that a higher genetically predicted vegetable intake was associated with a higher eGFR (percent change; ß: 3.071; 95% CI: 0.602, 0.560) but nonsignificantly associated with the risk of CKD (OR: 0.560; 95% CI: 0.289, 1.083) in the European ancestry data from the CKDGen. CONCLUSIONS: This study suggests that higher vegetable intake may have a causal effect on higher eGFRs in the European population.

Short or Long Sleep Duration and CKD: A Mendelian Randomization Study.

BACKGROUND: Studies have found sleeping behaviors, such as sleep duration, to be associated with kidney function and cardiovascular disease risk. However, whether short or long sleep duration is a causative factor for kidney function impairment has been rarely studied. METHODS: We studied data from participants aged 40-69 years in the UK Biobank prospective cohort, including 25,605 self-reporting short-duration sleep (<6 hours per 24 hours), 404,550 reporting intermediate-duration sleep (6-8 hours), and 35,659 reporting long-duration sleep (≥9 hours) in the clinical analysis. Using logistic regression analysis, we investigated the observational association between the sleep duration group and prevalent CKD stages 3-5, analyzed by logistic regression analysis. We performed Mendelian randomization (MR) analysis involving 321,260 White British individuals using genetic instruments (genetic variants linked with short- or long-duration sleep behavior as instrumental variables). We performed genetic risk score analysis as a one-sample MR and extended the finding with a two-sample MR analysis with CKD outcome information from the independent CKDGen Consortium genome-wide association study meta-analysis. RESULTS: Short or long sleep duration clinically associated with higher prevalence of CKD compared with intermediate duration. The genetic risk score for short (but not long) sleep was significantly related to CKD (per unit reflecting a two-fold increase in the odds of the phenotype; adjusted odds ratio, 1.80; 95% confidence interval, 1.25 to 2.60). Two-sample MR analysis demonstrated causal effects of short sleep duration on CKD by the inverse variance weighted method, supported by causal estimates from MR-Egger regression. CONCLUSIONS: These findings support an adverse effect of a short sleep duration on kidney function. Clinicians may encourage patients to avoid short-duration sleeping behavior to reduce CKD risk.

Pulse Oximeter Plethysmograph Variation During Hemorrhage in Beta-Blocker-Treated Swine.

BACKGROUND: Beta-blockers blunt the stress response to hemorrhage. Our aim was to investigate the feasibility of noninvasive pulse oximeter plethysmographic waveform variation (PoPV) for predicting blood volume loss in an esmolol-treated swine hemorrhagic shock model. MATERIALS AND METHODS: Controlled hemorrhage was induced in eight male domestic pigs. In four pigs, a total of 15% and 30% blood volume was drawn step-by-step over 10 min in each step (controlled hemorrhage-only pigs). In the other four pigs, the heart rate (HR) was reduced and maintained by 30% from baseline by esmolol infusion before controlled hemorrhage (esmolol-treated pigs). Diagnostic abilities of HR, pulse pressure variation (PPV), PoPV, and mean arterial pressure for 15% and 30% blood volume loss were determined by the area under the receiver operating characteristic curve (AUC). RESULTS: PoPV was well correlated with PPV in controlled hemorrhage-only pigs (r = 0.717) and esmolol-treated pigs (r = 0.532). In controlled hemorrhage-only pigs, HR (AUC = 0.841 and 0.864), PPV (0.878 and 0.843), and PoPV (0.779 and 0.793) accurately predicted 15% and 30% of blood volume loss. In esmolol-treated pigs, the diagnostic ability of HR was decreased (AUC = 0.766 and 0.733). However, diagnostic abilities of PPV (0.848 and 0.804) and PoPV (0.808 and 0.842) were not deteriorated. CONCLUSIONS: The diagnostic ability of HR for blood volume loss was blunted by esmolol. However, those of PPV and PoPV were not altered. PoPV may be considered to be a useful noninvasive tool to predict blood volume loss in injured patients taking beta-blockers.

Machine learning algorithm to predict mortality in patients undergoing continuous renal replacement therapy.

BACKGROUND: Previous scoring models such as the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) scoring systems do not adequately predict mortality of patients undergoing continuous renal replacement therapy (CRRT) for severe acute kidney injury. Accordingly, the present study applies machine learning algorithms to improve prediction accuracy for this patient subset. METHODS: We randomly divided a total of 1571 adult patients who started CRRT for acute kidney injury into training (70%, n = 1094) and test (30%, n = 477) sets. The primary output consisted of the probability of mortality during admission to the intensive care unit (ICU) or hospital. We compared the area under the receiver operating characteristic curves (AUCs) of several machine learning algorithms with that of the APACHE II, SOFA, and the new abbreviated mortality scoring system for acute kidney injury with CRRT (MOSAIC model) results. RESULTS: For the ICU mortality, the random forest model showed the highest AUC (0.784 [0.744-0.825]), and the artificial neural network and extreme gradient boost models demonstrated the next best results (0.776 [0.735-0.818]). The AUC of the random forest model was higher than 0.611 (0.583-0.640), 0.677 (0.651-0.703), and 0.722 (0.677-0.767), as achieved by APACHE II, SOFA, and MOSAIC, respectively. The machine learning models also predicted in-hospital mortality better than APACHE II, SOFA, and MOSAIC. CONCLUSION: Machine learning algorithms increase the accuracy of mortality prediction for patients undergoing CRRT for acute kidney injury compared with previous scoring models.

Emergency physician-based intensive care unit for critically ill patients visiting emergency department.

BACKGROUND: To provide a prompt and optimal intensive care to critically ill patients visiting our emergency department (ED), we set up and ran a specific type of emergency intensive care unit (EICU) managed by emergency physician (EP) intensivists. We investigated whether this EICU reduced the time interval from ED arrival to ICU transfer (ED-ICU interval) without altering mortality. METHODS: This was a retrospective study conducted in a tertiary referral hospital. We collected data from ED patients who were admitted to the EICU (EICU group) and other ICUs including medical, surgical, and cardiopulmonary ICUs (other ICUs group), from August 2014 to July 2017. We compared these two groups with respect to demographic findings, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, ED-ICU interval, ICU mortality, and hospital mortality. RESULTS: Among the 3440 critically ill patients who visited ED, 1815 (52.8%) were admitted to the EICU during the study period. The ED-ICU interval for the EICU group was significantly shorter than that for the other ICUs group by 27.5% (5.0 ±â€¯4.9 vs. 6.9 ±â€¯5.4 h, p < 0.001). In multivariable analysis, the ICU mortality (odds ratio = 1.062, 95% confidence interval 0.862-1.308, p = 0.571) and hospital mortality (odds ratio = 1.093, 95% confidence interval 0.892-1.338, p = 0.391) of the EICU group were not inferior to those of the other ICUs group. CONCLUSIONS: The EICU run by EP intensivists reduced the time interval from ED arrival to ICU transfer without altering hospital mortality.

Altered Risk for Cardiovascular Events With Changes in the Metabolic Syndrome Status: A Nationwide Population-Based Study of Approximately 10 Million Persons.

Background: Population-scale evidence for the association between dynamic changes in metabolic syndrome (MetS) status and alterations in the risk for major adverse cardiovascular events (MACE) is lacking. Objective: To investigate whether recovery from or development of MetS in a population is associated with an altered risk for MACE. Design: Nationwide cohort study. Setting: An analysis based on the National Health Insurance Database of Korea. Participants: A total of 27 161 051 persons who received national health screenings from 2009 to 2014 were screened. Those with a history of MACE were excluded. We determined the MetS status of 9 553 042 persons using the following harmonizing criteria: MetS-chronic (n = 1 486 485), MetS-developed (n = 587 088), MetS-recovery (n = 538 806), and MetS-free (n = 6 940 663). Measurements: The outcome was the occurrence of MACE, including acute myocardial infarction, revascularization, and acute ischemic stroke, identified from the claims database. The incidence rate ratios (IRRs) were calculated with adjustments for body mass index, comorbidity scores, previous metabolic variables, and other clinical or demographic variables. Results: At a median follow-up of 3.54 years, the MetS-recovery group (incidence rate, 4.55 per 1000 person-years) had a significantly lower MACE risk (adjusted IRR, 0.85 [95% CI, 0.83 to 0.87]) than that of the MetS-chronic group (incidence rate, 8.52 per 1000 person-years). The MetS-developed group (incidence rate, 6.05 per 1000 person-years) had a significantly higher MACE risk (adjusted IRR, 1.36 [CI, 1.33 to 1.39]) than that of the MetS-free group (incidence rate, 1.92 per 1000 person-years). Among the MetS components, change in hypertension was associated with the largest difference in MACE risk. Limitation: Limited assessment of mortality and short follow-up. Conclusion: Recovery from MetS was significantly associated with decreased risk for MACE, whereas development of MetS was associated with increased risk. Primary Funding Source: Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea.

Long-term impact of dialysis-requiring AKI during the perioperative period of liver transplantation on postdischarge outcomes.

BACKGROUND: Patients undergoing liver transplantation (LT) are prone to dialysis-requiring acute kidney injury (AKI-D). However, long-term prognoses among them need further investigation, as overall survival after LT is improving. METHODS: A nationwide, population-based cohort study was conducted using the data of Korean National Health Insurance System between 2006 and 2015. The patients who received dialysis during the perioperative period of LT were in the AKI-D group, and the control group included those who did not undergo dialysis. RESULTS: Among the 6879 patients who underwent LT, 968 were in the AKI-D group. All-cause mortality [adjusted hazard ratio (HR): 1.52 (1.26-1.83), P < 0.001], end-stage renal disease (ESRD) progression [adjusted HR: 2.93 (2.34-3.66), P < 0.001], and ICU readmission [adjusted HR: 1.70 (1.44-2.01), P < 0.001] within and after 90 days from discharge were increased in the AKI-D group. When analyzed among those who recovered from dialysis at discharge, overall outcomes were similar to those of the AKI-D group, except the long-term mortality. CONCLUSIONS: AKI-D during the perioperative period of LT was associated with worse mortality, ESRD progression, and ICU readmission risk. The results of renal-recovered patients could indicate clinicians that achievement of dialysis independence is important to gain favorable long-term postdischarge survival.

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.

Postdischarge Major Adverse Cardiovascular Events of ICU Survivors Who Received Acute Renal Replacement Therapy.

OBJECTIVES: Long-term risk of a major adverse cardiovascular events in ICU survivors who underwent acute renal replacement therapy requires further investigation. DESIGN: Nationwide population-based study using the claims database of Korea. SETTING: Index admission cases of ICU survivors in government-designated tertiary hospitals PATIENTS:: The study group consisted of ICU survivors who underwent acute renal replacement therapy, and the control group consisted of those without acute renal replacement therapy. Patients were excluded if they 1) were under age 20, 2) expired within 30 days after discharge, 3) received ICU care for less than 24 hours, 4) had a previous ICU admission, 5) had a history of major adverse cardiovascular event, or 6) had a major adverse cardiovascular event-related cardio/cerebrovascular diseases. The outcomes of the patients who received continuous renal replacement therapy were compared with those of patients who received only intermittent renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Information regarding patient characteristics and treatment modalities was collected and adjusted. The main outcome was major adverse cardiovascular event, including acute myocardial infarction, revascularization, and acute ischemic stroke. Patient mortality and progression to end-stage renal disease were also evaluated. We included 12,380 acute renal replacement therapy patients and 382,018 patients in the control group. Among the study group, 6,891 patients were included in the continuous renal replacement therapy group, and 5,034 in the intermittent renal replacement therapy group. The risks of major adverse cardiovascular event (adjusted hazard ratio, 1.463 [1.323-1.619]; p < 0.001), all-cause mortality (adjusted hazard ratio, 1.323 [1.256-1.393]; p < 0.001), and end-stage renal disease (adjusted hazard ratio, 18.110 [15.779-20.786]; p < 0.001) were higher in the acute renal replacement therapy patients than the control group. When we compared the continuous renal replacement therapy patients with the intermittent renal replacement therapy patients, the risk of major adverse cardiovascular event was comparable (adjusted hazard ratio, 1.049 [0.888-1.239]; p = 0.575). CONCLUSIONS: Clinicians should note the increased risk of a long-term major adverse cardiovascular event in acute renal replacement therapy patients and consider appropriate risk factor management. Significant difference in the risk of postdischarge major adverse cardiovascular event was not identified between continuous renal replacement therapy and intermittent renal replacement therapy.