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.

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.

Urine Methyl Hippuric Acid Levels in Acute Pesticide Poisoning: Estimation of Ingested Xylene Volume and Association with Clinical Outcome Parameters.

To determine the relationship between the oral ingestion volume of xylene and methyl hippuric acid (MHA) in urine, we measured MHA in 11 patients whose ingested xylene volume was identified. The best-fit equation between urine MHA and ingested amount of xylene was as follows: y (ingested amount of xylene, mL/kg) = -0.052x² + 0.756x (x = MHA in urine in g/g creatinine). From this equation, we estimated the ingested xylene volume in 194 patients who had ingested pesticide of which the formulation was not available. Our results demonstrated that oxadiazole, dinitroaniline, chloroacetamide, organophosphate, and pyrethroid were xylene-containing pesticide classes, while the paraquat, glyphosate, glufosinate, synthetic auxin, fungicide, neonicotinoid, and carbamate classes were xylene-free pesticides. Sub-group univariate analysis showed a significant association between MHA levels in urine and ventilator necessity in the pyrethroid group. However, this association was not observed in the organophosphate group. Our results suggest that MHA in urine is a surrogate marker for xylene ingestion, and high urine MHA levels may be a risk factor for poor clinical outcome with some pesticide poisoning.

Concurrent Hemoperfusion and Hemodialysis in Patients with Acute Pesticide Intoxication.

BACKGROUND: Water soluble and insoluble chemicals in the pesticide formulation may be eliminated more effectively in time if hemodialysis (HD) and hemoperfusion (HP) are performed concurrently. AIM: This study is aimed at evaluating the efficacy of concurrent HP and HD in patients with acute pesticide intoxication. METHODS: Between January 2011 and December 2012, we used HP and HD consecutively (HP-HD group, 347 cases), and then during the next 2 years (January 2013 to December 2014), we used concurrent HP and HD (HPD group, 383 cases). We compared the clinical outcomes between the 2 groups. RESULTS: The mortality was higher in the HP-HD group than in the HPD group: (48.1 vs. 20.9%) for the overall mortality and (81.8 vs. 57.9%) for the paraquat (bipyridylium) mortality (p < 0.001). In multiple logistic analyses, age (p = 0.013), ingested volume (p < 0.001), and HP-HD (p = 0.014) were significant risk factors for mortality in the paraquat ingested group. CONCLUSION: Concurrent HP and HD would be an effective and safe treatment for patients with acute pesticide intoxication, in particular, paraquat intoxication.

The Anion Gap is a Predictive Clinical Marker for Death in Patients with Acute Pesticide Intoxication.

Pesticide formulation includes solvents (methanol and xylene) and antifreeze (ethylene glycol) whose metabolites are anions such as formic acid, hippuric acid, and oxalate. However, the effect of the anion gap on clinical outcome in acute pesticide intoxication requires clarification. In this prospective study, we compared the anion gap and other parameters between surviving versus deceased patients with acute pesticide intoxication. The following parameters were assessed in 1,058 patients with acute pesticide intoxication: blood chemistry (blood urea nitrogen, creatinine, glucose, lactic acid, liver enzymes, albumin, globulin, and urate), urinalysis (ketone bodies), arterial blood gas analysis, electrolytes (Na(+), K(+), Cl(-) HCO3 (-), Ca(++)), pesticide field of use, class, and ingestion amount, clinical outcome (death rate, length of hospital stay, length of intensive care unit stay, and seriousness of toxic symptoms), and the calculated anion gap. Among the 481 patients with a high anion gap, 52.2% had a blood pH in the physiologic range, 35.8% had metabolic acidosis, and 12.1% had acidemia. Age, anion gap, pesticide field of use, pesticide class, seriousness of symptoms (all P < 0.001), and time lag after ingestion (P = 0.048) were significant risk factors for death in univariate analyses. Among these, age, anion gap, and pesticide class were significant risk factors for death in a multiple logistic regression analysis (P < 0.001). In conclusions, high anion gap is a significant risk factor for death, regardless of the accompanying acid-base balance status in patients with acute pesticide intoxication.

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.

TXNIP contributes to induction of pro-inflammatory phenotype and caspase-3 activation in astrocytes during Alzheimer's diseases.

Neuroinflammation and oxidative stress have been implicated in the pathogenesis of Alzheimer's disease (AD). Neuroinflammation and oxidative stress are associated with neuronal death in AD. Astrocytes are linked to neuroinflammation during AD. Astrocytes are important contributors to AD progression. Although the role of thioredoxin-interacting protein (TXNIP) has been identified in inflammation and oxidative stress, the mechanism by which TXNIP regulates inflammation and oxidative stress in astrocytes during AD remains unclear. In the present study, we found that TXNIP gene levels were elevated in cerebral cortex of patients with AD. The protein levels of TXNIP were elevated in GFAP-positive astrocytes of cerebral cortex from patients with AD and APP/PS1 double-transgenic mouse model of AD. Our results showed that TXNIP increased expression of genes related to pro-inflammatory reactive astrocytes and pro-inflammatory cytokines and chemokines in human astrocytes. Moreover, TXNIP increased production of pro-inflammatory cytokines and chemokines in human astrocytes. TXNIP induced activation of NK-kB signaling and over-production of mitochondrial reactive oxygen species (mtROS) in human astrocytes. TXNIP also induced mitochondrial oxidative stress by reduction of mitochondrial respiration and ATP production in human astrocytes. Furthermore, elevated TXNIP levels are correlated with caspase-3 activation of GFAP-positive astrocytes in patients with AD and mouse AD. TXNIP induced mitochondria-dependent apoptosis via caspase-9 and caspase-3 activation in human astrocytes. These results suggest that TXNIP contributes to induction of pro-inflammatory phenotype and caspase-3 activation in astrocytes during AD.

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.

A questionnaire survey on the diagnosis and treatment of Fabry nephropathy in clinical practice.

BACKGROUND: Fabry nephropathy is characterized by a deficiency of lysosomal alpha-galactosidase A, which results in proteinuria and kidney disease. The ineffectiveness of enzyme replacement therapy (ERT) for severe kidney failure highlights the need for early detection and meaningful markers. However, because the diagnosis and treatment of Fabry disease can vary according to the expertise of physicians, we evaluated the opinions of Korean specialists. METHODS: A questionnaire regarding the management of Fabry nephropathy was emailed to healthcare providers with the experience or ability to treat individuals with Fabry nephropathy. RESULTS: Of the 70 experts who responded to the survey, 43 were nephrologists, and 64.3% of the respondents reported having treated patients with Fabry disease. Pediatricians are treating primarily patients with classic types of the disease, while nephrologists and cardiologists are treating more patients with variant types. Only 40.7% of non-nephrologists agreed that a kidney biopsy was required at the time of diagnosis, compared with 81.4% of nephrologists. Thirty-eight of 70 respondents (54.3%) reported measuring globotriaosylsphingosine (lyso-Gb3) as a biomarker. The most common period to measure lyso-Gb3 was at the time of diagnosis, followed by after ERT, before ERT, and at screening. For the stage at which ERT should begin, microalbuminuria and proteinuria were chosen by 51.8% and 28.6% of respondents, respectively. CONCLUSION: Nephrologists are more likely to treat variant Fabry disease rather than classic cases, and they agree that ERT should be initiated early in Fabry nephropathy, using lyso-Gb3 as a biomarker.

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.

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.

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.

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.

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.

Blood Pressure Control in Patients with Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease. Blood pressure (BP) control can reduce the risks of cardiovascular (CV) morbidity, mortality, and kidney disease progression. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines have suggested the implementation of a more intensive BP control with a target systolic BP (SBP) of <120 mmHg based on the evidence that the CV benefits obtained is outweighed by the kidney injury risk associated with a lower BP target. However, an extremely low BP level may paradoxically aggravate renal function and CV outcomes. Herein, we aimed to review the existing literature regarding optimal BP control using medications for DKD.

Impact of Acid-Base Status on Mortality in Patients with Acute Pesticide Poisoning.

We investigated clinical impacts of various acid-base approaches (physiologic, base excess (BE)-based, and physicochemical) on mortality in patients with acute pesticide intoxication and mutual intercorrelated effects using principal component analysis (PCA). This retrospective study included patients admitted from January 2015 to December 2019 because of pesticide intoxication. We compared parameters assessing the acid-base status between two groups, survivors and non-survivors. Associations between parameters and 30-days mortality were investigated. A total of 797 patients were analyzed. In non-survivors, pH, bicarbonate concentration (HCO3-), total concentration of carbon dioxide (tCO2), BE, and effective strong ion difference (SIDe) were lower and apparent strong ion difference (SIDa), strong ion gap (SIG), total concentration of weak acids, and corrected anion gap (corAG) were higher than in survivors. In the multivariable logistic analysis, BE, corAG, SIDa, and SIDe were associated with mortality. PCA identified four principal components related to mortality. SIDe, HCO3-, tCO2, BE, SIG, and corAG were loaded to principal component 1 (PC1), referred as total buffer bases to receive and handle generated acids. PC1 was an important factor in predicting mortality irrespective of the pesticide category. PC3, loaded mainly with pCO2, suggested respiratory components of the acid-base system. PC3 was associated with 30-days mortality, especially in organophosphate or carbamate poisoning. Our study showed that acid-base abnormalities were associated with mortality in patients with acute pesticide poisoning. We reduced these variables into four PCs, resembling the physicochemical approach, revealed that PCs representing total buffer bases and respiratory components played an important role in acute pesticide poisoning.