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1.
Article in English | MEDLINE | ID: mdl-38934043

ABSTRACT

Background: The global coronavirus disease 2019 (COVID-19) pandemic has placed patients with end-stage kidney disease (ESKD) at heightened risk owing to their vulnerability to infections. Our study focused on patients with ESKD, examining COVID-19 incidence, hospitalization, and mortality in relation to their renal replacement therapy (RRT) type and identifying factors influencing COVID-19 hospitalization. Methods: We conducted a retrospective cohort study using health insurance claims data from the Health Insurance Review and Assessment Service for patients with ESKD between July 2017 and June 2022. COVID-19 data for the general population were sourced from the Korea Disease Control and Prevention Agency. Results: Patients undergoing hemodialysis (HD) constituted 90.7% of the cohort, followed by kidney transplantation (KT) recipients and peritoneal dialysis (PD). After adjusting for every 10,000 individuals, KT recipients exhibited the highest COVID-19 incidence, followed by those undergoing HD and PD, whereas the general population showed a higher infection rate of 43.64. Patients undergoing HD had the highest hospitalization rates, followed by KT recipients and those undergoing PD. The mortality rate per 10,000 individuals was highest in HD, followed by PD, the general population, and KT. Multivariate analysis indicated that age, RRT duration, residence in a nursing hospital, and comorbidities were associated with COVID-19 hospitalization. Conclusion: Among RRT modalities, KT recipients displayed the highest COVID-19 incidence, whereas those undergoing HD exhibited the highest hospitalization and mortality rates. This study contributes to our understanding of infectious diseases in patients on RRT and aids in preparedness for future infectious disease outbreaks.

2.
RSC Adv ; 14(15): 10172-10181, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38544945

ABSTRACT

Transition metal hydroxides are commonly used to develop nanostructures with desired functionalities by controlling their size, morphology, and structure. In this study, nickel hydroxide nanosheets with a hexagonal island shape are synthesized via a surfactant-assisted method. Using this method, nickel hydroxide nanosheets can be easily achieved in a quick manner. The synthesized nanosheets are 3-6 nm thick and exhibit a curly and wrinkled morphology with increasing surfactant concentration. These nanosheets demonstrate superior catalytic properties for the oxygen evolution reaction activity compared to nickel oxide sheets obtained via a simple heat treatment. Furthermore, we conduct surface enhanced Raman scattering analysis to confirm that the nickel hydroxide nanosheets serve as active species for NiOOH during the oxygen evolution reaction, and we propose an electrochemical mechanism for this system. This study not only presents the detailed synthesis process but also proposes a straightforward approach, offering valuable insights into the structural and electrochemical properties of the resulting nanosheets.

3.
Biomark Res ; 12(1): 22, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38331932

ABSTRACT

Hemodialysis patients are susceptible to cardiovascular remodeling, which increases the risk of cardiovascular morbidity and mortality. Circulating extracellular matrix (ECM)-associated molecules increase during cardiovascular remodeling and can be potential biomarkers of adverse cardiovascular outcomes. However, their clinical significance in patients undergoing hemodialysis remain unclear. This study aimed to elucidate the association between circulating ECM-associated molecules and cardiovascular outcomes in patients undergoing hemodialysis. To this end, we measured levels of plasma matrix metalloproteinase (MMP)-2, MMP-9, tenascin-C, and thrombospondin-2 in 372 patients with hemodialysis. Plasma MMP-2 levels were significantly higher in patients with future cardiovascular events than in those without future cardiovascular events (P = 0.004). All measured molecules had significant correlations with amino-terminal pro-brain natriuretic peptide levels, but the correlation coefficient was the strongest for plasma MMP-2 (rho = 0.317, P < 0.001). High plasma MMP-2 levels were predictive of left ventricular (LV) diastolic dysfunction (adjusted odds ratio per a standard deviation increase = 1.48, 95% confidence interval [CI] = 1.05-2.08) and were independently associated with an increased risk of composite cardiovascular events (adjusted hazard ratio per a standard deviation increase = 1.30, 95% CI = 1.04-1.63). In conclusion, high plasma MMP-2 levels are associated with LV diastolic dysfunction and an increased risk of adverse cardiovascular outcomes in hemodialysis patients.

4.
Intern Med ; 63(6): 773-780, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-37558487

ABSTRACT

Objective Contrast agents used for radiological examinations are an important cause of acute kidney injury (AKI). We developed and validated a machine learning and clinical scoring prediction model to stratify the risk of contrast-induced nephropathy, considering the limitations of current classical and machine learning models. Methods This retrospective study included 38,481 percutaneous coronary intervention cases from 23,703 patients in a tertiary hospital. We divided the cases into development and internal test sets (8:2). Using the development set, we trained a gradient boosting machine prediction model (complex model). We then developed a simple model using seven variables based on variable importance. We validated the performance of the models using an internal test set and tested them externally in two other hospitals. Results The complex model had the best area under the receiver operating characteristic (AUROC) curve at 0.885 [95% confidence interval (CI) 0.876-0.894] in the internal test set and 0.837 (95% CI 0.819-0.854) and 0.850 (95% CI 0.781-0.918) in two different external validation sets. The simple model showed an AUROC of 0.795 (95% CI 0.781-0.808) in the internal test set and 0.766 (95% CI 0.744-0.789) and 0.782 (95% CI 0.687-0.877) in the two different external validation sets. This was higher than the value in the well-known scoring system (Mehran criteria, AUROC=0.67). The seven precatheterization variables selected for the simple model were age, known chronic kidney disease, hematocrit, troponin I, blood urea nitrogen, base excess, and N-terminal pro-brain natriuretic peptide. The simple model is available at http://52.78.230.235:8081/Conclusions We developed an AKI prediction machine learning model with reliable performance. This can aid in bedside clinical decision making.


Subject(s)
Acute Kidney Injury , Clinical Decision-Making , Humans , Risk Assessment/methods , Retrospective Studies , Machine Learning , Acute Kidney Injury/chemically induced , Acute Kidney Injury/diagnosis
5.
Medicine (Baltimore) ; 102(40): e35412, 2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37800776

ABSTRACT

RATIONALE: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic stem cell disease with features of hemolytic anemia, thrombosis, and bone marrow failure. Due to intravascular hemolysis and hemoglobinuria, renal dysfunction is often accompanied in PNH patients. PATIENT CONCERNS: A 25-year old woman presenting gross hematuria after coronavirus disease 2019 infection was admitted to our medical center. She had mild nausea and headache. She was diagnosed with iron deficiency anemia few years ago and had no other underlying disease. Her laboratory findings showed acute kidney injury (AKI) and severe anemia, with evidences of hemolysis. DIAGNOSIS: Renal biopsy was done to determine the cause of renal failure and the result was acute tubular necrosis with deposition of golden pigments, hemosiderin. With pathologic result and laboratory finding of hemolysis, we did flow cytometry for PNH, and the patient was finally diagnosed with PNH. INTERVENTIONS: With AKI and oliguria, the patient started to take hemodialysis. OUTCOMES: After taking 5 sessions of hemodialysis, the patient's renal function was recovered from AKI. With diagnosis of PNH, the patient is now being treated with complement C5 inhibitor. LESSONS: This challenging case tells us that we should consider the first manifestation of PNH as a cause of severe AKI requiring hemodialysis in a patient with anemia and evidence of hemolysis.


Subject(s)
Acute Kidney Injury , Hemoglobinuria, Paroxysmal , Adult , Female , Humans , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Acute Kidney Injury/pathology , Hemoglobinuria, Paroxysmal/complications , Hemoglobinuria, Paroxysmal/diagnosis , Hemolysis , Hemosiderin/adverse effects , Renal Dialysis
6.
Medicine (Baltimore) ; 102(39): e35484, 2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37773791

ABSTRACT

Vaccination is important for patients undergoing hemodialysis (HD) to prevent coronavirus disease 2019 (COVID-19) infection since they are more vulnerable. However, they exhibit a weak response to vaccines, underscoring the importance of understanding whether antibodies are sufficiently produced and their durability post-COVID-19 vaccination. This prospective observational study assessed the antibody response of Korean patients undergoing HD for 1 year. We compared the antibody responses of patients undergoing HD to the COVID-19 vaccine with those of healthy volunteers from 2021 to 2022. The patient and control groups received 2 doses of ChAdOx1 nCoV-19 and mRNA-1273, respectively. Immunoglobulin G (IgG) and neutralizing antibody levels were measured weeks or months apart after 2 doses for 1 year using enzyme-linked immunosorbent and fluorescence-based competitive severe acute respiratory syndrome coronavirus 2 neutralizing assays, respectively. We analyzed the third dose's effect on the patient group by categorizing the group into patients who received the third dose and those who did not since it was initiated midway through the study. In the control group, we enrolled participants who had completed 3 doses of mRNA-1273 since almost all participants received the third dose. Thirty-two patients undergoing HD and 15 healthy participants who received 2 doses of ChAdOx1 nCoV-19 and 3 of mRNA-1273, respectively, were enrolled. Although antibody production was weaker in the patient group than in the control group (P < .001), patients showed an increase in IgG levels (0.408 ± 0.517 optical density (OD) pre-vaccination, 2.175 ± 1.241 OD in patients with 2 doses, and 2.134 ± 1.157 OD in patients with 3 doses 1 year after the second dose) and neutralizing antibodies (23 ± 8% pre-vaccination, 87 ± 23% in patients with 2 doses, and 89 ± 18% in patients with 3 doses 1 year after the second dose) post-vaccination (P < .001). In the patient group, 19 patients received a third dose (BNT162b2 or mRNA-1273); however, it did not increase the antibody levels (P = 1.000). Furthermore, the antibodies produced by the vaccination did not wane until 1 year. Two doses of vaccination resulted in a significant antibody response in patients undergoing HD, and antibody levels did not wane until 1 year.


Subject(s)
2019-nCoV Vaccine mRNA-1273 , COVID-19 , Humans , Antibody Formation , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , ChAdOx1 nCoV-19 , SARS-CoV-2 , Vaccination , Antibodies, Neutralizing , Immunoglobulin G , Antibodies, Viral
7.
Clin Exp Vaccine Res ; 12(3): 249-259, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37599806

ABSTRACT

Purpose: Since patients on hemodialysis (HD) are known to be vulnerable to coronavirus disease 2019 (COVID-19), many studies were conducted regarding the effectiveness of the COVID-19 vaccine in HD patients in Western countries. Here, we assessed antibody response of HD patients for 6 months post-vaccination to identify the duration and effectiveness of the COVID-19 vaccine in the Asian population. Materials and Methods: We compared antibody response of the COVID-19 vaccine in HD patients with healthy volunteers. Patient and control groups had two doses of ChAdOx1 nCoV-19 and mRNA-1273, respectively. Immunoglobulin G (IgG) was measured before vaccination, 2 weeks after the first dose, 2 and 4 weeks, 3 and 6 months after the second dose. Neutralizing antibody was measured before vaccination and at 2 weeks, 3 and 6 months after second dose. Since the third dose was started in the middle of the study, we analyzed the effect of the third dose as well. Results: Although antibody production was weaker than the control group (n=22), the patient group (n=39) showed an increase in IgG and neutralizing antibody after two doses. And, 21/39 patients and 14/22 participants had a third dose (BNT162b2 or mRNA-1273 in the patient group, mRNA-1273 in the control group), and it did not affect antibody response in both group. Trend analysis showed IgG and neutralizing antibody did not decrease over time. Age, sex, and HD vintage did not affect antibody production in HD patients. Patients with higher body mass index displayed better seroresponse, while those on immunosuppressants showed poor seroresponse. Conclusion: Two doses of vaccination led to significant antibody response in HD patients, and the antibody did not wane until 6 months.

8.
J Pers Med ; 13(1)2023 Jan 12.
Article in English | MEDLINE | ID: mdl-36675812

ABSTRACT

Systemic inflammation has been proposed as a relevant factor of vascular remodeling and dysfunction. We aimed to identify circulating inflammatory biomarkers that could predict future arteriovenous fistula (AVF) dysfunction in patients undergoing hemodialysis. A total of 282 hemodialysis patients were enrolled in this prospective multicenter cohort study. Plasma cytokine levels were measured at the time of data collection. The primary outcome was the occurrence of AVF stenosis and/or thrombosis requiring percutaneous transluminal angioplasty or surgery within the first year of enrollment. AVF dysfunction occurred in 38 (13.5%) patients during the study period. Plasma interleukin-6 (IL-6) levels were significantly higher in patients with AVF dysfunction than those without. Diabetes mellitus, low systolic blood pressure, and statin use were also associated with AVF dysfunction. The cumulative event rate of AVF dysfunction was the highest in IL-6 tertile 3 (p = 0.05), and patients in tertile 3 were independently associated with an increased risk of AVF dysfunction after multivariable adjustments (adjusted hazard ratio = 3.06, p = 0.015). In conclusion, circulating IL-6 levels are positively associated with the occurrence of incident AVF dysfunction in hemodialysis patients. Our data suggest that IL-6 may help clinicians identify those at high risk of impending AVF failure.

9.
Nanoscale Horiz ; 7(10): 1210-1216, 2022 Sep 26.
Article in English | MEDLINE | ID: mdl-35929511

ABSTRACT

Transition metal oxides, which include many stoichiometric variations, are formed into various crystal structures by the atomic arrangement of cations and anions according to stoichiometric composition and are used for a wide range of applications based on this. Among them, cobalt oxide, which has wide crystal structures depending on the lattice points of the anion and the valence of the Co cation, from its hydroxide formula, is attracting a lot of attention due to its interesting catalytic properties due to its crystal structure. In this study, using the synthesized Co(OH)2 nanosheets, the real-time behavior of the phase transition that occurs when continuous heat is applied to the sample has been systematically analyzed using an aberration-corrected scanning transmission electron microscope. The layered Co(OH)2 phase passes through hexagonal CoO and cubic CoO phases to finally become Co nanoparticles, but when the temperature is dropped in the hexagonal phase, spinel Co3O4 is formed. These results suggest that various phases included in transition metal oxides can be selectively implemented according to temperature range control.

10.
Nanoscale Horiz ; 7(10): 1250, 2022 Sep 26.
Article in English | MEDLINE | ID: mdl-35972207

ABSTRACT

Correction for 'Thermally driven phase transition of cobalt hydroxide sheets via cobalt oxides to cobalt nanoparticles' by Aram Yoon et al., Nanoscale Horiz., 2022, https://doi.org/10.1039/d2nh00218c.

11.
Appl Microsc ; 52(1): 7, 2022 Jul 14.
Article in English | MEDLINE | ID: mdl-35831511

ABSTRACT

The process of encapsulating cobalt nanoparticles using a graphene layer is mainly direct pyrolysis. The encapsulation structure of hybrids prepared in this way improves the catalyst stability, which greatly reduces the leaching of non-metals and prevents metal nanoparticles from growing beyond a certain size. In this study, cobalt particles surrounded by graphene layers were formed by increasing the temperature in a transmission electron microscope, and they were analyzed using scanning transmission electron microscopy (STEM). Synthesized cobalt hydroxide nanosheets were used to obtain cobalt particles using an in-situ heating holder inside a TEM column. The cobalt nanoparticles are surrounded by layers of graphene, and the number of layers increases as the temperature increases. The interlayer spacing of the graphene layers was also investigated using atomic imaging. The success achieved in the encapsulation of metallic nanoparticles in graphene layers paves the way for the design of highly active and reusable heterogeneous catalysts for more challenging molecules.

12.
Environ Res ; 212(Pt A): 113177, 2022 09.
Article in English | MEDLINE | ID: mdl-35346654

ABSTRACT

For the first time, both spatial and temporal effects of fish feed on changes in abundance of antibiotic resistance genes (ARGs) were investigated in South Korea via quantifying ARGs and analyzing physicochemical parameters in the influent (IN) and effluent before (BF) and 30 min after (AF) the fish feeding time of sixteen flow-through fish farms. The absolute abundance of ARGs in AF samples was 5 times higher than in BF and 12 times higher than in IN samples. Values of physicochemical parameters such as ammonia, total nitrogen, suspended solids and turbidity in the effluent significantly increased by 21.6, 4.2, 2.6 and 1.65 times, respectively, after fish feeding. Spatially, the fish farms on Jeju Island exhibited higher relative abundance (3.02 × 10-4 - 6.1 × 10-2) of ARGs compared to the farms in nearby Jeollanam-do (3.4 × 10-5 - 8.3 × 10-3). Seasonally, samples in summer and autumn showed a higher abundance of ARGs than in winter and spring. To assess risk to the food chain as well as public health, further studies are warranted to explore the pathogenic potential of these ARGs.


Subject(s)
Aquaculture , Genes, Bacterial , Animals , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial/genetics , Fisheries , Fishes
13.
Sci Rep ; 12(1): 3107, 2022 02 24.
Article in English | MEDLINE | ID: mdl-35210536

ABSTRACT

The incidence of fractures in patients with end-stage kidney disease (ESKD) is high which is associated with high morbidity and mortality. Since fractures are preventable diseases to some extent, epidemiologic studies are needed a lot. The aim of this study is to explore the epidemiology of fractures by modality of kidney replacement therapy (KRT). We performed a retrospective analysis of 52,777 patients dependent on KRT from 2008 to 2017 using the National Health Insurance System of Republic Korea. Fractures were occurred in 8995 (17.04%) of 52,777 patients with ESKD. Hemodialysis and kidney transplant patients had the highest (57.4 per 1000 person-year) and the lowest (25.2 per 1000 person-year) incidence rate, respectively. The two most common fracture sites were the lower limb and upper limb, regardless of KRT modality. The first fractures were about 2.55 ± 2.07 years after KRT initiation, the earliest in Hemodialysis patients. Diabetes mellitus, cerebrovascular disease, chronic lung and liver disease were risk factors of fractures. The use of steroids, anti-osteoporosis medications, and some classes of psychotropics and opioids was associated with an elevated risk. The results of this study inform the understanding of fractures in KRT patients.


Subject(s)
Fractures, Bone/epidemiology , Fractures, Bone/etiology , Renal Replacement Therapy/adverse effects , Adult , Aged , Female , Humans , Incidence , Kidney Failure, Chronic/therapy , Kidney Transplantation , Male , Middle Aged , Renal Dialysis , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors
14.
Pharmaceutics ; 14(2)2022 Feb 16.
Article in English | MEDLINE | ID: mdl-35214161

ABSTRACT

Vonoprazan (VPZ) is the first-in-class potassium-competitive acid blocker (P-CAB), and has many advantages over proton pump inhibitors (PPIs). It is administered as a fumarate salt for the treatment of acid-related diseases, including reflux esophagitis, gastric ulcer, and duodenal ulcer, and for eradication of Helicobacter pylori. To discover novel cocrystals of VPZ, we adopted an artificial neural network (ANN)-based machine learning model as a virtual screening tool that can guide selection of the most promising coformers for VPZ cocrystals. Experimental screening by liquid-assisted grinding (LAG) confirmed that 8 of 19 coformers selected by the ANN model were likely to create new solid forms with VPZ. Structurally similar benzenediols and benzenetriols, i.e., catechol (CAT), resorcinol (RES), hydroquinone (HYQ), and pyrogallol (GAL), were used as coformers to obtain phase pure cocrystals with VPZ by reaction crystallization. We successfully prepared and characterized three novel cocrystals: VPZ-RES, VPZ-CAT, and VPZ-GAL. VPZ-RES had the highest solubility among the novel cocrystals studied here, and was even more soluble than the commercially available fumarate salt of VPZ in solution at pH 6.8. In addition, novel VPZ cocrystals had superior stability in aqueous media than VPZ fumarates, demonstrating their potential for improved pharmaceutical performance.

15.
Kidney Res Clin Pract ; 41(2): 231-241, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34974656

ABSTRACT

BACKGROUND: The limited literature on mental illness in end-stage kidney disease (ESKD) patients suggests that this disease is common and burdensome but underrecognized in clinical practice. This study aimed to analyze the prevalence of mental illness in ESKD patients. METHODS: We assessed the prevalence and patterns of mental illnesses in a nationwide cohort of patients diagnosed with ESKD between January 1, 2008, and December 31, 2017. The risk of mental illness was evaluated using a multivariable Cox proportional hazards model. RESULTS: A total of 70,079 patients met all study inclusion criteria. A total of 28.3% of patients had mental illness, and the specific distribution was as follows: depression, 16.8%; anxiety, 20.0%; somatoform/conversion disorder, 0.9%; stress reaction/adjustment disorder, 2.5%; and substance abuse disorder, 0.6%. The frequency of mental illness was highest in patients on hemodialysis (HD), followed by patients on peritoneal dialysis (PD) and kidney transplant (KT) patients. The peak rate of mental illness in HD and PD patients was reached 1 to 2 years after renal replacement therapy initiation, but the peak rate of most mental illnesses in KT patients occurred before surgery. The prevalence of depression was 2.19 times higher in HD patients and 1.97 times higher in PD patients than in KT patients. CONCLUSION: ESKD patients are at high risk of mental illness, and the prevalence of mental illness is highest in HD patients. Since the onset of mental illness occurs around the initiation of renal replacement therapy, clinicians need to pay attention to mental illness when treating ESKD patients.

16.
Biomed Res Int ; 2021: 5504873, 2021.
Article in English | MEDLINE | ID: mdl-34853790

ABSTRACT

Chronic kidney disease-mineral bone disorder (CKD-MBD) is the most common complication in CKD patients. Although there is a consensus on treatment guidelines for CKD-MBD, it remains uncertain whether these treatment recommendations reflect actual practice. Therefore, the aim of this study was to investigate the CKD-MBD medication trend in real-world practice. This was a retrospective and observational study using a 12-year period database transformed into a common data model from three tertiary university hospitals. Study populations were subjects initially diagnosed as CKD. The date of diagnosis was designated as the index date. New patients were categorized year to year from 2008 to 2019 with a fixed observation period of 365 days to check the prescription of CKD-MBD medications including calcium-containing phosphate binder, noncalcium-containing phosphate binder, aluminium hydroxide, vitamin D receptor activator (VDRA), and cinacalcet. The numbers of CKD patients in the three hospitals were 7555, 2424, and 5351, respectively. The proportion for patients with CKD-MBD medication prescription decreased yearly regardless of hospital and CKD stage (p for trend < 0.05). The use of aluminium hydroxide disappeared steadily while the use of VDRA increased annually in all settings. Despite these changes in prescription patterns, the mean value for CKD-MBD-related serologic markers was almost within target range. The proportion of the population within the target value was not significantly changed. Irrespective of hospital and CKD stage, similar trends of prescription for CKD-MBD medications were observed in real-world practice. Further research with a distributed network study may be helpful to understand medication trends in CKD-MBD treatment.


Subject(s)
Chronic Kidney Disease-Mineral and Bone Disorder/drug therapy , Adult , Aged , Aged, 80 and over , Calcium-Regulating Hormones and Agents/therapeutic use , Chronic Kidney Disease-Mineral and Bone Disorder/etiology , Cinacalcet/therapeutic use , Electronic Health Records , Female , Hospitals, University , Humans , Male , Middle Aged , Practice Guidelines as Topic , Receptors, Calcitriol/agonists , Renal Insufficiency, Chronic/complications , Republic of Korea , Retrospective Studies , Tertiary Care Centers
17.
PLoS One ; 16(11): e0260135, 2021.
Article in English | MEDLINE | ID: mdl-34788311

ABSTRACT

BACKGROUND: Melanoma-associated antigen H1 (MAGEH1) is a protein that belongs to melanoma-associated antigen (MAGE) superfamily. Growth arrest and DNA damage 45G (GADD45G) is a member of the DNA damage-inducible gene family which responds to environmental stresses. We have previously shown that GADD45G is a protein that promotes apoptosis of renal tubular cells in response to a nephrotoxic injury. In this study, we show evidence that MAGEH1 interacts with GADD45G and is involved in the induction of nephrotoxin-induced apoptosis of renal tubular cells. METHODS: Primary human renal tubular epithelial (HRE) cells and human kidney 2 (HK-2) cells were used in this study. To produce stable cell lines in which MAGEH1 expression was silenced, HRE cells were transduced with a lentiviral vector encoding a single guide RNA construct targeting the MAGEH1 gene. To knockdown GADD45G expression in HRE cells, a vector containing short hairpin RNA (shRNA) was used. We used short interfering RNAs (siRNA) to achieve transient silencing of genes in HK-2 cells. Recombinant adenoviruses were synthesized to overexpress MAGEH1 and GADD45G proteins. Human protein microarray was used to identify proteins that binds to GADD45G. Co-immunoprecipitation assays were then performed to confirm microarray results. Cell death was induced by cyclosporine A (CsA). Real-time quantitative PCR assay was used to evaluate gene expression levels. The degree of apoptosis and necrosis of cultured cells was evaluated by flow cytometry. Expression levels of caspases were examined using western blot analysis. RESULTS: We found that GADD45G bound to one protein spotted in the protein microarray, which was subsequently identified as MAGEH1. We confirmed the interaction between GADD45G and MAGEH1 protein using the co-immunoprecipitation assay. MAGEH1 gene expression was not altered by CsA-induced cytotoxic injury, whereas GADD45G gene expression was increased significantly upon CsA treatment. MAGEH1 expression was significantly downregulated in GADD45G knockdown HRE stable cells suggesting that MAGEH1 expression may be dependent on GADD45G expression. CsA-induced apoptosis was significantly reduced in MAGEH1 knockdown HRE stable cells which led to an increased survival of these cells. Similar results were observed in GADD45G knockdown HRE stable cells. Accordingly, CsA-induced apoptosis was significantly decreased in MAGEH1 siRNA and GADD45G siRNA transfected HK-2 cells. CsA-induced activation of caspase-7 and caspase-9 was inhibited in MAGEH1 knockdown HRE stable cells, and similarly in GADD45G knockdown HRE stable cells. CONCLUSIONS: To the best of our knowledge, this is the first study to show that MAGEH1 interacts with GADD45G and that MAGEH1 is involved in caspase-dependent apoptosis of renal tubular cells induced by nephrotoxic drugs.


Subject(s)
Epithelial Cells , Apoptosis , Caspase 7 , Cell Death , DNA Damage , Humans , Kidney
18.
Kidney Res Clin Pract ; 40(3): 419-431, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34510861

ABSTRACT

BACKGROUND: Optimal estimated glomerular filtration rate (eGFR) to start maintenance dialysis is controversial. Observational studies have reported that initiation of dialysis at high eGFRs is associated with worse postdialysis survival. METHODS: We retrospectively investigated 1,038 incident dialysis patients who started maintenance dialysis during 2010-2015. Patients were assessed for comorbidities and adverse events during the transitional period of dialysis initiation. Patients were classified as planned dialysis (PD) vs. unplanned dialysis (UD) according to indications for dialysis initiation. RESULTS: UD group comprised 352 patients (33.9%). Mean eGFR at dialysis initiation was higher in UD patients than PD patients (7.9 ± 5.1 vs. 5.9 ± 3.4 mL/min/1.73 m2, p < 0.001). Mean Davies comorbidity index in the UD group was higher (vs. PD group, 1.3 ± 1.0 vs. 0.9 ± 1.0, p < 0.001). Patients with more comorbidities experienced more ischemic heart disease (hazard ratio [HR], 4.36; 95% confidence interval [CI], 1.71-11.14) in the medium-risk group and HR of 8.84 (95% CI, 3.06-25.55) in the high-risk group (vs. low-risk group, p < 0.001)) during the predialysis period. High-risk group had increased postdialysis mortality (HR, 2.48; 95% CI, 1.46-4.20; p = 0.001). Adjusted HR of mortality was higher in the medium-risk group of UD patients (HR, 1.72; 95% CI, 1.16-2.56; p = 0.007). CONCLUSION: Patients with more comorbidities were at increased risk of predialysis ischemic heart disease and postdialysis mortality. UD patients in the medium-risk population had increased risk of postdialysis mortality. Dialysis start should be individualized by considering comorbidities.

19.
Foods ; 10(7)2021 Jul 09.
Article in English | MEDLINE | ID: mdl-34359470

ABSTRACT

A probiotic powder of poor flowability with high dust content, prepared by spray drying reconstituted skim milk fermented with Lactobacillus rhamnosus GG (LGG), was granulated by fluidized-bed granulation (FBG). The effects of the addition of skim milk powder (SMP) as a fluidizing aid, and of simple moisture-activation with or without dehydration, were investigated with respect to the performance of the FBG process. A fine, poorly fluidizable LGG powder (Geldart Group C) could be fluidized and granulated, with a 4- to 5-fold increase in particle size (d4,3 = 96-141 µm), by mixing with SMP (30-50%), which has larger, fluidizable particles belonging to Geldart Group A. Moisture-activation after the mixing, followed by fluidized-bed dehydration with hot air to remove excess moisture, further improved the FBG; the yield of the granules increased from 42% to 61% and the particle size distribution became much narrower, although the average particle size remained almost the same (d4,3 = 142 µm). These granules showed a popcorn-type structure in scanning electron microscopy images and encapsulated a sufficient level of viable LGG cells (1.6 × 108 CFU g-1). These granules also exhibited much better flowability and dispersibility than the spray-dried LGG powder.

20.
Sci Rep ; 11(1): 3929, 2021 02 16.
Article in English | MEDLINE | ID: mdl-33594123

ABSTRACT

Patients with end-stage kidney disease (ESKD) have been reported to have an increased risk of cancer. However, the epidemiological characteristics of cancer in ESKD patients remain unclear. Therefore, this study aimed to investigate the epidemiological characteristics of cancer in ESKD patients and the differences based on the renal replacement therapy provided. Data on ESKD patients were obtained from the South Korean nationwide cohort Health Insurance Review and Assessment Service database. This study included 58,831 eligible patients of the total 813,907 patients diagnosed with ESKD between January 1, 2007 and December 31, 2017. Of the 58,831 ESKD patients, 3292 (5.6%) were newly diagnosed with cancer. The average duration between the diagnosis of ESKD and cancer was 3.3 ± 1.9 years (mean ± standard deviation), with no differences between hemodialysis, peritoneal dialysis, and kidney transplant groups. The most commonly observed cancer sites in ESKD patients were the colorectum, lung, and liver. The incidence of cancer increased progressively among patients undergoing kidney transplant, peritoneal dialysis, and hemodialysis in that order. Hemodialysis patients were found to have an increased risk of digestive tract cancer compared with kidney transplant patients (adjusted hazard ratio = 1.9; 95% confidence interval: 1.31-2.81; P < 0.001). The study findings may be a useful reference for cancer-screening guidelines.


Subject(s)
Kidney Failure, Chronic/complications , Neoplasms/epidemiology , Aged , Female , Humans , Incidence , Kidney Failure, Chronic/therapy , Kidney Transplantation/statistics & numerical data , Male , Middle Aged , Peritoneal Dialysis/statistics & numerical data , Republic of Korea/epidemiology , Retrospective Studies
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