Abdominal periaortic and renal sinus fat attenuation indices measured on computed tomography are associated with metabolic syndrome.

OBJECTIVES: To investigate the association between abdominal periaortic (APA) and renal sinus (RS) fat attenuation index (FAI) measured on MDCT and metabolic syndrome in non-obese and obese individuals. METHODS: Visceral, subcutaneous, RS, and APA adipose tissue were measured in preoperative abdominal CT scans of individuals who underwent donor nephrectomy (n = 84) or bariatric surgery (n = 155). FAI was defined as the mean attenuation of measured fat volume. Participants were categorized into four groups: non-obese without metabolic syndrome (n = 64), non-obese with metabolic syndrome (n = 25), obese without metabolic syndrome (n = 21), and obese with metabolic syndrome (n = 129). The volume and FAI of each fat segment were compared among the groups. Receiver operator characteristics curve analysis was used to assess the association between the FAIs and metabolic syndrome. RESULTS: FAIs of all abdominal fat segments were significantly lower in the obese group than in the non-obese group (p < 0.001). RS, APA, and the visceral adipose tissue FAIs were significantly lower in participants with metabolic syndrome than in those without metabolic syndrome in the non-obese group (p < 0.001, p = 0.006, and p < 0.001, respectively). The area under the curve for predicting metabolic syndrome was significantly higher for APA FAI (0.790) than subcutaneous, visceral, and RS FAI in all groups (0.649, 0.647, and 0.655, respectively). CONCLUSION: Both metabolic syndrome and obesity were associated with lower RS and APA adipose tissue FAI, and APA FAI performed best for predicting metabolic syndrome. KEY POINTS: • The volume and FAI of RS, APA, and visceral adipose tissue showed opposite trends with regard to metabolic syndrome or obesity. • Both metabolic syndrome and obesity were associated with lower RS FAI and APA FAI. • APA FAI performed best for predicting metabolic syndrome among FAIs of abdominal fat segments.

Tomographic Imaging of Mucociliary Clearance Following Maxillary Sinus Augmentation: A Case Series.

Mucociliary clearance (MCC) allows ventilation of graft particles that are displaced through a perforated Schneiderian membrane during maxillary sinus augmentation (MSA). However, it is very rarely confirmed by cone-beam computed tomographic (CBCT) images. It is not yet known how long the dislodged bone graft particles remain in the maxillary sinus or how quickly they are ventilated after MSA. The purpose of these case reports is to introduce tomographic imaging of ventilation of bone graft particles displaced through a perforated Schneiderian membrane after MSA. Four patients, who needed implant placement in the posterior maxilla, received MSA, during which the Schneiderian membrane was perforated but was not repaired. Therefore, some bone graft particles were dislocated into the sinus cavity. The sizes of the perforated membranes were measured and recorded. CBCT scans were taken at multiple time points after the surgery to visualize and trace the ejected material. In addition, the time from when the bone graft substitute was delivered to the sinus until the CBCT scans were taken was recorded. The expelled bone graft particles migrated to the ostium along the sinus wall immediately after MSA on CBCT images taken immediately after the surgery. No displaced graft particles were observed in the maxillary sinus on CBCT scans after 1 week. The CBCT scans at 6 months showed no unusual radiographic images. Within the limitations of the case reports, tomographic imaging revealed an MCC system that allows displaced graft particles to be ventilated into the ostium very early during MSA healing and not stagnate in the maxillary sinus.

Validation of an international prediction model including the Oxford classification in Korean patients with IgA nephropathy.

BACKGROUND: Recently, a new international risk prediction model including the Oxford classification was published which was validated in a large multi-ethnic cohort. Therefore, we aimed to validate this risk prediction model in Korean patients with IgA nephropathy. METHODS: This retrospective cohort study was conducted with 545 patients who diagnosed IgA nephropathy with renal biopsy in three medical centers. The primary outcome was defined as a reduction in estimated glomerular filtration rate (eGFR) of >50% or incident end-stage renal disease (ESRD). Continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI) were used to validate models. RESULTS: During the median 3.6 years of follow-up period, 53 (9.7%) renal events occurred. In multivariable Cox regression model, M1 (hazard ratio [HR], 2.22; 95% confidence interval [CI], 1.02-4.82; p = .043), T1 (HR, 2.98; 95% CI, 1.39-6.39; p = .005) and T2 (HR, 4.80; 95% CI, 2.06-11.18; p < .001) lesions were associated with increased risk of renal outcome. When applied the international prediction model, the area under curve (AUC) for 5-year risk of renal outcome was 0.69, which was lower than previous validation and internally derived models. Moreover, cNRI and IDI analyses showed that discrimination and reclassification performance of the international model was inferior to the internally derived models. CONCLUSION: The international risk prediction model for IgA nephropathy showed not as good performance in Korean patients as previous validation in other ethnic group. Further validation of risk prediction model is needed for Korean patients with IgA nephropathy.

Developing an Individual Glucose Prediction Model Using Recurrent Neural Network.

In this study, we propose a personalized glucose prediction model using deep learning for hospitalized patients who experience Type-2 diabetes. We aim for our model to assist the medical personnel who check the blood glucose and control the amount of insulin doses. Herein, we employed a deep learning algorithm, especially a recurrent neural network (RNN), that consists of a sequence processing layer and a classification layer for the glucose prediction. We tested a simple RNN, gated recurrent unit (GRU), and long-short term memory (LSTM) and varied the architectures to determine the one with the best performance. For that, we collected data for a week using a continuous glucose monitoring device. Type-2 inpatients are usually experiencing bad health conditions and have a high variability of glucose level. However, there are few studies on the Type-2 glucose prediction model while many studies performed on Type-1 glucose prediction. This work has a contribution in that the proposed model exhibits a comparative performance to previous works on Type-1 patients. For 20 in-hospital patients, we achieved an average root mean squared error (RMSE) of 21.5 and an Mean absolute percentage error (MAPE) of 11.1%. The GRU with a single RNN layer and two dense layers was found to be sufficient to predict the glucose level. Moreover, to build a personalized model, at most, 50% of data are required for training.

Association of Intracranial Artery Calcification with Cognitive Impairment in Hemodialysis Patients.

BACKGROUND Chronic kidney disease (CKD) is one of risk factors for dementia and cognitive decline. Cardiovascular and dialysis-related factors might also be involved in the mechanism of cognitive impairment in hemodialysis patients. The objective of this study was to investigate whether cardiovascular risk factors including intracranial artery calcification and dialysis-related factors such as fibroblast growth factor 23 (FGF23) might be associated with cognitive impairment in hemodialysis patients. MATERIAL AND METHODS A cross-sectional observational study included patients receiving in-center hemodialysis over 6 months at our hospital. All patients underwent non-contrast computed tomography (CT) examinations. Internal carotid artery (ICA) calcium scores were measured using the Agatston method. The Korean version of the Montreal Cognitive Assessment was used for measurement of cognitive function at each study visit. Serum concentrations of FGF23, osteoprotegerin, and klotho were analyzed using commercial enzyme-linked immunosorbent assay kits. RESULTS This study included 69 patients. Cognitive impairment was observed in 22 patients (31.9%), including 3 patients with dementia. ICA calcium score in patients with cognitive impairment was higher than that in those without cognitive impairment (177.3 versus 87.6, P=0.022). Intracranial artery calcification was significantly associated with cognitive impairment after adjusting for FGF23 and 25-OH vitamin D, but not significant after adjusting for age, FGF23, and 25-OH vitamin D. Low level of FGF23 was associated with cognitive impairment. CONCLUSIONS Intracranial artery calcification and low FGF23 could be associated with cognitive impairment in hemodialysis patients. Longitudinal studies are needed to investigate whether intracranial artery calcification and FGF23 could affect cognitive function of hemodialysis patients.

A machine learning-based approach for predicting renal function recovery in general ward patients with acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a significant challenge in healthcare. While there are considerable researches dedicated to AKI patients, a crucial factor in their renal function recovery, is often overlooked. Thus, our study aims to address this issue through the development of a machine learning model to predict restoration of kidney function in patients with AKI. METHODS: Our study encompassed data from 350,345 cases, derived from three hospitals. AKI was classified in accordance with the Kidney Disease: Improving Global Outcomes. Criteria for recovery were established as either a 33% decrease in serum creatinine levels at AKI onset, which was initially employed for the diagnosis of AKI. We employed various machine learning models, selecting 43 pertinent features for analysis. RESULTS: Our analysis contained 7,041 and 2,929 patients' data from internal cohort and external cohort respectively. The Categorical Boosting Model demonstrated significant predictive accuracy, as evidenced by an internal area under the receiver operating characteristic (AUROC) of 0.7860, and an external AUROC score of 0.7316, thereby confirming its robustness in predictive performance. SHapley Additive exPlanations (SHAP) values were employed to explain key factors impacting recovery of renal function in AKI patients. CONCLUSION: This study presented a machine learning approach for predicting renal function recovery in patients with AKI. The model performance was assessed across distinct hospital settings, which revealed its efficacy. Although the model exhibited favorable outcomes, the necessity for further enhancements and the incorporation of more diverse datasets is imperative for its application in real- world.

The effect of a scenario-based cognitive behavioral therapy mobile app on end-stage kidney disease patients on dialysis.

It has been reported that a scenario-based cognitive behavioral therapy mobile app including Todac Todac was effective in improving depression in the general public. However, no study has been conducted on whether Todac Todac is effective in dialysis patients. Therefore, this study was intended to determine whether the use of this app was effective in improving depression in dialysis patients. Sixty-five end-stage kidney disease patients receiving dialysis at Soonchunhyang University Cheonan Hospital were randomly assigned to the Todac Todac app program (experimental group) or an E-moods daily mood chart app program (control group) for 3 weeks. The degree of depression was measured before and after using the app.After the end of the 3-week program, a small but significant improvement was observed in the Trait anxiety (p < 0.05) and Beck depression index (p < 0.05) in E-moods group and DAS-K scores (p < 0.05) in Todac Todac group. However, no differences were seen in any parameters between the two groups. In addition, Todac Todac was not statistically more effective than the control intervention in the subgroup analysis. The Todac Todac, a scenario-based cognitive behavioral therapy mobile app, seemed to have a limited effect on improving depression in dialysis patients. Therefore, it is necessary to develop new tools to improve depression in dialysis patients.

Kidney biopsy can help to predict renal outcomes of patients with type 2 diabetes mellitus.

Background: In patients with type 2 diabetes mellitus (T2DM), diabetic kidney disease (DKD) is diagnosed based on clinical features. A kidney biopsy is used only in selected cases. This study aimed to reconsider the role of a biopsy in predicting renal outcomes. Methods: Clinical and laboratory parameters and renal biopsy results were obtained from 237 patients with T2DM who underwent renal biopsies at Soonchunhyang University Cheonan Hospital between January 2000 and March 2020 and were analyzed. Results: Of 237 diabetic patients, 29.1% had DKD only, 61.6% had non-DKD (NDKD), and 9.3% had DKD with coexisting NDKD (DKD/NDKD). Of the patients with DKD alone, 43.5% progressed to end-stage kidney disease (ESKD), while 15.8% of NDKD patients and 36.4% of DKD/NDKD patients progressed to ESKD (p < 0.001). In the DKD-alone group, pathologic features like ≥50% global sclerosis (p < 0.001), tubular atrophy (p < 0.001), interstitial fibrosis (p < 0.001), interstitial inflammation (p < 0.001), and the presence of hyalinosis (p = 0.03) were related to worse renal outcomes. The Cox regression model showed a higher risk of progression to ESKD in the DKD/NDKD group compared to the DKD-alone group (hazard ratio [HR], 2.73; p = 0.032), ≥50% global sclerosis (HR, 3.88; p < 0.001), and the degree of mesangial expansion (moderate: HR, 2.45; p = 0.045 and severe: HR, 6.22; p < 0.001). Conclusion: In patients with T2DM, a kidney biopsy can help in identifying patients with NDKD for appropriate treatment, and it has predictive value.

RIPK3 causes mitochondrial dysfunction and albuminuria in diabetic podocytopathy through PGAM5-Drp1 signaling.

BACKGROUND: Receptor-interacting protein kinase (RIPK)3 is an essential molecule for necroptosis and its role in kidney fibrosis has been investigated using various kidney injury models. However, the relevance and the underlying mechanisms of RIPK3 to podocyte injury in albuminuric diabetic kidney disease (DKD) remain unclear. Here, we investigated the role of RIPK3 in glomerular injury of DKD. METHODS: We analyzed RIPK3 expression levels in the kidneys of patients with biopsy-proven DKD and animal models of DKD. Additionally, to confirm the clinical significance of circulating RIPK3, RIPK3 was measured by ELISA in plasma obtained from a prospective observational cohort of patients with type 2 diabetes, and estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), which are indicators of renal function, were followed up during the observation period. To investigate the role of RIPK3 in glomerular damage in DKD, we induced a DKD model using a high-fat diet in Ripk3 knockout and wild-type mice. To assess whether mitochondrial dysfunction and albuminuria in DKD take a Ripk3-dependent pathway, we used single-cell RNA sequencing of kidney cortex and immortalized podocytes treated with high glucose or overexpressing RIPK3. RESULTS: RIPK3 expression was increased in podocytes of diabetic glomeruli with increased albuminuria and decreased podocyte numbers. Plasma RIPK3 levels were significantly elevated in albuminuric diabetic patients than in non-diabetic controls (p = 0.002) and non-albuminuric diabetic patients (p = 0.046). The participants in the highest tertile of plasma RIPK3 had a higher incidence of renal progression (hazard ratio [HR] 2.29 [1.05-4.98]) and incident chronic kidney disease (HR 4.08 [1.10-15.13]). Ripk3 knockout improved albuminuria, podocyte loss, and renal ultrastructure in DKD mice. Increased mitochondrial fragmentation, upregulated mitochondrial fission-related proteins such as phosphoglycerate mutase family member 5 (PGAM5) and dynamin-related protein 1 (Drp1), and mitochondrial ROS were decreased in podocytes of Ripk3 knockout DKD mice. In cultured podocytes, RIPK3 inhibition attenuated mitochondrial fission and mitochondrial dysfunction by decreasing p-mixed lineage kinase domain-like protein (MLKL), PGAM5, and p-Drp1 S616 and mitochondrial translocation of Drp1. CONCLUSIONS: The study demonstrates that RIPK3 reflects deterioration of renal function of DKD. In addition, RIPK3 induces diabetic podocytopathy by regulating mitochondrial fission via PGAM5-Drp1 signaling through MLKL. Inhibition of RIPK3 might be a promising therapeutic option for treating DKD.

Computed tomography evaluation of skeletal muscle quality and quantity in people with morbid obesity with and without metabolic abnormality.

We investigated the differences in quantity and quality of skeletal muscle between metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) individuals using abdominal CT. One hundred and seventy-two people with morbid obesity who underwent bariatric surgery and 64 healthy control individuals participated in this retrospective study. We divided the people with morbid obesity into an MHO and MUO group. In addition, nonobese metabolic healthy people were included analysis to provide reference levels. CT evaluation of muscle quantity (at the level of the third lumbar vertebra [L3]) was performed by calculating muscle anatomical cross-sectional area (CSA), which was normalized to patient height to produce skeletal muscle index (SMI). Muscle quality was assessed as skeletal muscle density (SMD), which was calculated from CT muscle attenuation. To characterize intramuscular composition, muscle attenuation was classified into three categories using Hounsfield unit (HU) thresholds: -190 HU to -30 HU for intermuscular adipose tissue (IMAT), -29 to +29 HU for low attenuation muscle (LAM), and +30 to +150 HU for normal attenuation muscle (NAM). People with morbid obesity comprised 24 (14%) MHO individuals and 148 (86%) MUO individuals. The mean age of the participants was 39.7 ± 12.5 years, and 154 (65%) participants were women. MUO individuals had a significantly greater total skeletal muscle CSA than MHO individuals in the model that adjusted for all variables. Total skeletal muscle SMI, SMD, NAM index, LAM index, and IMAT index did not differ between MHO and MUO individuals for all adjusted models. Total skeletal muscle at the L3 level was not different in muscle quantity, quality, or intramuscular composition between the MHO and MUO individuals, based on CT evaluation. MHO individuals who are considered "healthy" should be carefully monitored and can have a similar risk of metabolic complications as MUO individuals, at least based on an assessment of skeletal muscle.

Indoxyl sulfate induces apoptotic cell death by inhibiting glycolysis in human astrocytes.

Background: Neurologic complications, such as cognitive and emotional dysfunction, have frequently been observed in chronic kidney disease (CKD) patients. Previous research shows that uremic toxins play a role in the pathogenesis of CKD-associated cognitive impairment. Since astrocytes contribute to the protection and survival of neurons, astrocyte function and brain metabolism may contribute to the pathogenesis of neurodegeneration. Indoxyl sulfate (IS) is the most popular uremic toxin. However, how IS-induced astrocyte injury brings about neurologic complications in CKD patients has not been elucidated. Methods: The rate of extracellular acidification was measured in astrocytes when IS (0.5-3 mM, 4 or 7 days) treatment was applied. The hexokinase 1 (HK1), pyruvate kinase isozyme M2 (PKM2), pyruvate dehydrogenase (PDH), and phosphofructokinase (PFKP) protein levels were also measured. The activation of the apoptotic pathway was investigated using a confocal microscope, fluorescence-activated cell sorting, and cell three-dimensional imaging was used. Results: In astrocytes, IS affected glycolysis in not only dose-dependently but also time-dependently. Additionally, HK1, PKM2, PDH, and PFKP levels were decreased in IS-treated group when compared to the control. The results were prominent in cases with higher doses and longer exposure duration. The apoptotic features after IS treatment were also observed. Conclusion: Our results showed that the inhibition of glycolysis by IS in astrocytes leads to cell death via apoptosis. Specifically, long-term and higher-dose exposures had more serious effects on astrocytes. Our results suggest that the glycolysis pathway and related targets could provide a novel approach to cognitive dysfunction in CKD patients.

Loss of Cutibacterium is responsible for chronic kidney disease-associated pruritus in patients on dialysis.

Background: Chronic kidney disease (CKD)-associated pruritus is a severe distressing condition that frequently occurs in patients undergoing dialysis. In this study, the profile of the skin microbiome was analyzed to understand the underlying etiology and potential treatments. Methods: Seventy-six end-stage kidney disease (ESKD) patients (hemodialysis, 40; peritoneal dialysis, 36) and 15 healthy controls were enrolled and swabbed at three sites: back, antecubital fossa, and shin. The pruritus severity of the enrolled subjects was validated by the Worst Itch Numeric Rating Scale (WI-NRS), 5-D itch scale, and Uremic Pruritus in Dialysis Patients (UP-Dial). The 16S gene-based metagenomics method was applied to skin microbiome analysis. Results: In the comparison of bacterial communities of ESKD patients and the control group, there was a significant difference on back. Specifically, the average composition ratio of the Cutibacterium in the back samples was significantly lower in ESKD patients than in healthy controls (p < 0.01). In further analysis of ESKD patients, Cutibacterium was significantly lower in the high pruritus group than in the low pruritus group (p < 0.05), even though other clinical parameters such as age, calcium-phosphorus product, and intact parathyroid hormone showed no significance difference between the groups. Conclusion: In ESKD patients, the skin microbiome of the back was significantly altered, and the severity of itching was related to the reduction of Cutibacterium. This research reveals the relationship between skin microbiota and CKD-associated pruritus in multiple skin sites for the first time. The results of this study suggest a potential data basis for the diagnosis and treatment of CKD-associated pruritus.

Genome-wide association study and fine-mapping on Korean biobank to discover renal trait-associated variants.

Background: Chronic kidney disease is a significant health burden worldwide, with increasing incidence. Although several genome-wide association studies (GWAS) have investigated single nucleotide polymorphisms (SNP) associated with kidney trait, most studies were focused on European ancestry. Methods: We utilized clinical and genetic information collected from the Korean Genome and Epidemiology Study (KoGES). Results: More than five million SNPs from 58,406 participants were analyzed. After meta-GWAS, 1,360 loci associated with estimated glomerular filtration rate (eGFR) at a genome-wide significant level (p = 5 × 10-8) were identified. Among them, 399 loci were validated with at least one other biomarker (blood urea nitrogen [BUN] or eGFRcysC) and 149 loci were validated using both markers. Among them, 18 SNPs (nine known ones and nine novel ones) with 20 putative genes were found. The aggregated effect of genes estimated by MAGMA gene analysis showed that these significant genes were enriched in kidney-associated pathways, with the kidney and liver being the most enriched tissues. Conclusion: In this study, we conducted GWAS for more than 50,000 Korean individuals and identified several variants associated with kidney traits, including eGFR, BUN, and eGFRcysC. We also investigated functions of relevant genes using computational methods to define putative causal variants.

The Higher the CKD Stage, the Higher the Psychological Stress in Patients with CKD during COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic is related to psychological distress. Such distress depends on various factors. We previously reported that hemodialysis patients have more psychological distress than peritoneal dialysis patients among patients on dialysis in the COVID-19 pandemic era. However, no study has reported how psychological distress related to the COVID-19 pandemic depends on renal function in the entire group of chronic kidney disease (CKD) patients. Therefore, the objective of this study was to investigate psychological distress and concerns related to COVID-19 according to CKD stage. This was a cross-sectional study that included 397 CKD patients who visited a hospital from August 2020 to November 2020. Patients responded to questionnaires covering depression (9-item Patient Health Questionnaire, PHQ-9), anxiety (7-item Generalized Anxiety Disorder, GAD-7), psychological impact of event (22-item Impact of Event Scale-Revised, IES-R), insomnia (7-item Insomnia severity Index, ISI), concerns, and precautionary measures about COVID-19. According to eGFR and dialysis status, patients were divided into three groups: (1) patients with CKD stage 1~2, (2) patients with CKD stage 3~5 without dialysis, and (3) dialysis patients. The higher the CKD stage, the higher the GAD-7 (p = 0.009) and the ISI score (p = 0.001). When patients with CKD stage 1~2 and CKD stage 3~5 (with or without dialysis) were compared, PHQ-9 (p = 0.026), GAD-7 (p = 0.010), and ISI score (p = 0.002) were higher in the CKD stage 3~5 group. However, when comparing those with and without dialysis, only the ISI score (p = 0.008) showed a significant difference. More severe kidney dysfunction in CKD patients was associated with more psychological distress during the COVID-19 pandemic. Therefore, as CKD stage increases, more attention should be paid to the mental care of these patients.

Arrhythmia and Heart Rate Variability during Long Interdialytic Periods in Patients on Maintenance Hemodialysis: Prospective Observational Cohort Study.

Sudden cardiac death among hemodialysis patients is related to the hemodialysis schedule. Mortality is highest within 12 h before and after the first hemodialysis sessions of a week. We investigated the association of arrhythmia occurrence and heart rate variability (HRV) using an electrocardiogram (ECG) monitoring patch during the long interdialytic interval in hemodialysis patients. This was a prospective observational study with 55 participants on maintenance hemodialysis for at least six months. A patch-type ECG monitoring device was applied to record arrhythmia events and HRV during 72 h of a long interdialytic period. Forty-nine participants with sufficient ECG data out of 55 participants were suitable for the analysis. The incidence of supraventricular tachycardia and ventricular tachycardia did not significantly change over time. The square root of the mean squared differences of successive NN intervals (RMSSD), the proportion of adjacent NN intervals differing by >50 ms (pNN50), and high-frequency (HF) increased during the long interdialytic interval. The gap in RMSSD, pNN50, HF, and the low-frequency/high-frequency (LF/HF) ratio between patients with and without significant arrhythmias increased significantly over time during the long interdialytic interval. The daily changes in RMSSD, pNN50, HF, and the LF/HF ratio were more prominent in patients without significant arrhythmias than in those with significant arrhythmias. The electrolyte fluctuation between post-hemodialysis and subsequent pre-hemodialysis was not considered in this study. The study results suggest that the decreased autonomic response during interdialytic periods in dialysis patients is associated with poor cardiac arrhythmia events.

Clinical Safety of Expanded Hemodialysis Compared with Hemodialysis Using High-Flux Dialyzer during a Three-Year Cohort.

Expanded hemodialysis (HD) equipped with a medium cut-off (MCO) membrane provides superior removal of larger middle molecules. However, there is still little research on the long-term benefits of expanded HD. Over a three-year period, this observational study evaluated the efficacy and safety profile of expanded HD for inflammatory cytokines, including IL-6. We conducted a prospective cohort study to investigate the inflammatory cytokine changes and a retrospective observational cohort study to investigate long-term clinical efficacy and safety over a three-year period. We categorized the patients according to dialyzer used: MCO and high-flux (HF) dialyzer. The inflammatory cytokines, including IFN-γ, IL-1ß, IL-6, and TNF-α, were measured annually. The concentrations and changes of the four cytokines over time did not differ between the HF group (n = 15) and MCO group (n = 27). In both prospective and retrospective (HF group, n = 38; MCO group, n = 76) cohorts, there were no significant differences in either death, cardiovascular events, infections, or hospitalizations. Furthermore, the temporal changes in laboratory values, including serum albumin and erythropoietin prescriptions, did not differ significantly between the two groups in either the prospective or retrospective cohorts. In conclusion, clinical efficacy and safety outcomes, as well as inflammatory cytokines, did not differ with expanded HD compared with HF dialysis during a three-year treatment course, although the level of inflammatory cytokine was stable.

Transiently Observed Trace Albuminuria on Urine Dipstick Test Is Associated With All-Cause Death, Cardiovascular Death, and Incident Chronic Kidney Disease: A National Health Insurance Service-National Sample Cohort in Korea.

Introduction: Albuminuria is a well-known risk factor for end-stage kidney disease, all-cause mortality, and cardiovascular mortality, even when the albumin-to-creatinine ratio is <30 mg/g. However, the association between transiently observed trace albuminuria and these major adverse outcomes has not yet been reported. This study aimed to examine the effect of transient albuminuria on these major adverse outcomes using the National Health Insurance Service data in Korea. Methods and Results: The National Health Insurance Service-National Sample Cohort from Korea, followed from 2002 to 2015, consisted of 1,025,340 individuals, accounting for 2.2% of the total Korean population. We analyzed the effect of transient albuminuria on all-cause death, cardiovascular death, and incident chronic kidney disease (CKD) and compared it with the group without albuminuria. Among 1,025,340 individuals, 121,876 and 2,815 had transient albuminuria and no albuminuria, respectively. Adjusted hazard ratios of the transient albuminuria group for cardiovascular death and incident CKD were 1.76 (1.01-3.08) and 1.28 (1.15-1.43), respectively. There were significant differences in all-cause death, cardiovascular death, and incident CKD between the two groups after propensity score matching (p = 0.0037, p = 0.015, and p < 0.0001, respectively). Propensity score matching with bootstrapping showed that the hazard ratios of the transient albuminuria group for all-cause death and cardiovascular death were 1.39 (1.01-1.92) and 2.18 (1.08-5.98), respectively. Conclusions: In this nationwide, large-scale, retrospective cohort study, transient albuminuria was associated with all-cause death, cardiovascular death, and incident CKD, suggesting that transient albuminuria could be a risk marker for adverse outcomes in the future, and that its own subclinical phenotype could play an important role during the course of CKD.

Prediction Model of Acute Respiratory Failure in Patients with Acute Pesticide Poisoning by Intentional Ingestion: Prediction of Respiratory Failure in Pesticide Intoxication (PREP) Scores in Cohort Study.

Acute respiratory failure is the primary cause of mortality in patients with acute pesticide poisoning. The aim of the present study was to develop a new and efficient score system for predicting acute respiratory failure in patients with acute pesticide poisoning. This study was a retrospective observational cohort study comprised of 679 patients with acute pesticide poisoning by intentional poisoning. We divided this population into a ratio of 3:1; training set (n = 509) and test set (n = 170) for model development and validation. Multivariable logistic regression models were used in developing a score-based prediction model. The Prediction of Respiratory failure in Pesticide intoxication (PREP) scoring system included a summation of the integer scores of the following five variables; age, pesticide category, amount of ingestion, Glasgow Coma Scale, and arterial pH. The PREP scoring system developed accurately predicted respiratory failure (AUC 0.911 [0.849-0.974], positive predictive value 0.773, accuracy 0.873 in test set). We came up with four risk categories (A, B, C and D) using PREP scores 20, 40 and 60 as the cut-off for mechanical ventilation requirement risk. The PREP scoring system developed in the present study could predict respiratory failure in patients with pesticide poisoning, which can be easily implemented in clinical situations. Further prospective studies are needed to validate the PREP scoring system.

Cognitive Sequelae and Hippocampal Dysfunction in Chronic Kidney Disease following 5/6 Nephrectomy.

Neurological disorders are prevalent in patients with chronic kidney disease (CKD). Vascular factors and uremic toxins are involved with cognitive impairment in CKD. In addition, vascular dementia-induced alterations in the structure and function of the hippocampus can lead to deficits in hippocampal synaptic plasticity and cognitive function. However, regardless of this clinical evidence, the pathophysiology of cognitive impairment in patients with CKD is not fully understood. We used male Sprague Dawley rats and performed 5/6 nephrectomy to observe the changes in behavior, field excitatory postsynaptic potential, and immunostaining of the hippocampus following CKD progression. We measured the hippocampus volume on magnetic resonance imaging scans in the controls (n = 34) and end-stage renal disease (ESRD) hemodialysis patients (n = 42). In four cognition-related behavior assays, including novel object recognition, Y-maze, Barnes maze, and classical contextual fear conditioning, we identified deficits in spatial working memory, learning and memory, and contextual memory, as well as the ability to distinguish familiar and new objects, in the rats with CKD. Immunohistochemical staining of Na+/H+ exchanger1 was increased in the hippocampus of the CKD rat models. We performed double immunofluorescent staining for aquaporin-4 and glial fibrillary acidic protein and then verified the high coexpression in the hippocampus of the CKD rat model. Furthermore, results from recoding of the field excitatory postsynaptic potential (fEPSP) in the hippocampus showed the reduced amplitude and slope of fEPSP in the CKD rats. ESRD patients with cognitive impairment showed a significant decrease in the hippocampus volume compared with ESRD patients without cognitive impairment or the controls. Our findings suggest that uremia resulting from decreased kidney function may cause the destruction of the blood-brain barrier and hippocampus-related cognitive impairment in CKD.

Pericoronary fat attenuation index in computed tomography angiography is associated with mortality in end-stage renal disease.

BACKGROUND: An increased pericoronary fat attenuation index (FAI) on computed tomography angiography (CTA) is associated with increased all-cause and cardiac mortality in the general population. However, the ability of pericoronary FAI to predict long-term outcomes in chronic kidney disease (CKD) patients is unknown. METHODS: In this single-center retrospective longitudinal cohort study, we assessed the utility of CTA-based pericoronary FAI measurement to predict mortality of CKD patients, including those with end-stage renal disease (ESRD). Mapping and analysis of pericoronary FAI involved three major proximal coronary arteries. The prognostic value of pericoronary FAI for long-term mortality was assessed with multivariable Cox regression models. RESULTS: Among 268 CKD participants who underwent coronary CTA, 209 participants with left anterior descending artery (LAD) FAI measurements were included. The pericoronary FAI measured at the LAD was not significantly associated with adjusted risk of allcause mortality (hazard ratio [HR], 2.08; 95% confidence interval [CI], 0.94-3.51) in any CKD group. However, ESRD patients with elevated pericoronary FAI values had a greater adjusted risk of all-cause mortality compared with the low-FAI group (HR, 2.26; 95% CI, 1.11-4.61). CONCLUSION: The pericoronary FAI measured at the LAD predicted long-term mortality in patients with ESRD, which could provide an opportunity for early primary intervention in ESRD patients.