288 results on '"Der-Cherng Tarng"'
Search Results
2. 2022 Taiwan lipid guidelines for primary prevention
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Po-Hsun Huang, Ya-Wen Lu, Yi-Lin Tsai, Yen-Wen Wu, Hung-Yuan Li, Hsin-Yun Chang, Chih-Hsing Wu, Chih-Yu Yang, Der-Cherng Tarng, Chin-Chou Huang, Li-Ting Ho, Chao-Feng Lin, Shih-Chieh Chien, Yih-Jer Wu, Hung-I Yeh, Wen-Harn Pan, and Yi-Heng Li
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General Medicine - Published
- 2022
3. Echocardiographic features of left ventricular dysfunction and outcomes in chronic kidney disease
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Shuo-Ming Ou, Chieh-Ju Chao, Ming-Tsun Tsai, Kuo-Hua Lee, Wei-Cheng Tseng, Pin-Jie Bin, Yao-Ping Lin, Chien-Yi Hsu, and Der-Cherng Tarng
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Cardiology and Cardiovascular Medicine - Abstract
ObjectiveHeart failure (HF) imposes a substantial burden and the prevalence of HF is high in patients with chronic kidney disease (CKD). HF results in multiple hospital admissions, but whether HF subtypes worsen long-term outcomes and renal function in patients with CKD remains inconclusive.MethodsThe study comprised 10 904 patients with CKD aged ≥20 years who underwent echocardiography between 1 January 2011 and 31 December 2018. The patients were stratified into four groups: non-HF, HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and HF with preserved ejection fraction (HFpEF). The primary end points were all-cause mortality, major adverse cardiovascular events (MACEs) and adverse renal outcomes.ResultsIn inverse probability of treatment weighting-adjusted method, the risk of all-cause mortality and MACEs relative to the non-HF group was greatest in the HFrEF group (HR 3.18 (95% CI 2.57 to 3.93) and HR 3.83 (95% CI 3.20 to 4.59)), followed by the HFmrEF (HR 2.75 (95% CI 2.22 to 3.42) and HR 3.08 (95% CI 2.57 to 3.69)) and HFpEF (HR 1.85 (95% CI 1.59 to 2.15) and HR 2.43 (95% CI 2.16 to 2.73) groups. In addition, the HFrEF group had the greatest risks of end-stage renal disease (HR 2.58 (95% CI 1.94 to 3.44)) compared with other groups.ConclusionsHF is associated with subsequent worse clinical outcomes, which may be more pronounced in patients with HFrEF, followed by those with HFmrEF and those with HFpEF relative to non-HF group.
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- 2022
4. Novel Anemia Therapies in CKD: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference
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Elaine Ku, Lucia Del Vecchio, Kai-Uwe Eckardt, Volker H. Haase, Kirsten L. Johansen, Masaomi Nangaku, Navdeep Tangri, Sushrut S. Waikar, Andrzej Więcek, Michael Cheung, Michel Jadoul, Wolfgang C. Winkelmayer, David C. Wheeler, Baris Afsar, Tadao Akizawa, Stefan D. Anker, Mustafa Arici, Jodie L. Babitt, Jonathan Barratt, Jeffrey S. Berns, Anatole Besarab, Sunil Bhandari, Christopher Brown, Aleix Cases, Glenn M. Chertow, Cynthia Delgado, Tillman B. Drüeke, Steven Fishbane, Rafael Gómez, Morgan E. Grams, Takayuki Hamano, Chuan-Ming Hao, Raymond K. Hsu, Kunitoshi Iseki, Isabelle Jordans, Edgar V. Lerma, Francesco Locatelli, Iain C. Macdougall, Jolanta Małyszko, Patrick Maxwell, Lawrence P. McMahon, Gregorio T. Obrador, Marlies Ostermann, Roberto Pecoits-Filho, Farzana Perwad, Simon D. Roger, Ajay K. Singh, Laura Solá, Bruce S. Spinowitz Mai Sugahara, Toshiyuki Takahashi, Mototsugu Tanaka, Tetsuhiro Tanaka, Der-Cherng Tarng, Marcello Tonelli, Yusuke Tsukamoto, Carl P. Walther, Angela Yee-Moon Wang, Bradley A. Warady, Angela C. Webster, Matthew R. Weir, Jay B. Wish, and Muh Geot Wong
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Nephrology - Published
- 2023
5. Plasma Galectin-9 Is a Useful Biomarker for Predicting Renal Function in Patients Undergoing Native Kidney Biopsy
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Ming-Tsun, Tsai, Ruey-Bing, Yang, Shuo-Ming, Ou, Wei-Cheng, Tseng, Kuo-Hua, Lee, Chih-Yu, Yang, Fu-Pang, Chang, and Der-Cherng, Tarng
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Medical Laboratory Technology ,General Medicine ,Pathology and Forensic Medicine - Abstract
Context.— Galectin-9 reduces tissue damage in certain immune-mediated glomerular diseases. However, its role in structural and functional renal changes in patients with varying types of chronic kidney disease (CKD) is less clear. Objective.— To investigate the association between plasma galectin-9 levels, proteinuria, tubulointerstitial lesions, and renal function in different CKD stages. Design.— We measured plasma galectin-9 levels in 243 patients undergoing renal biopsy for determining the CKD etiology. mRNA and protein expression levels of intrarenal galectin-9 were assessed by quantitative real-time polymerase chain reaction and immunostaining. Relationships between plasma galectin-9, clinical characteristics, and tubulointerstitial damage were analyzed with logistic regression. We investigated galectin-9 expression patterns in vitro in murine J774 macrophages treated with differing stimuli. Results.— To analyze the relationship between galectin-9 and clinical features, we divided the patients into 2 groups according to median plasma galectin-9 levels. The high galectin-9 group tended to be older and to have decreased renal function, higher proteinuria, and greater interstitial fibrosis. After multivariable adjustment, elevated plasma galectin-9 levels were independently associated with stage 3b or higher CKD. An analysis of gene expression in the tubulointerstitial compartment in the biopsy samples showed a significant positive correlation between intrarenal galectin-9 mRNA expression and plasma galectin-9 levels. Immunohistochemistry confirmed increased galectin-9 expression in the renal interstitium of patients with advanced CKD, and most galectin-9–positive cells were macrophages, as determined by double-immunofluorescence staining. In vitro experiments showed that galectin-9 expression in macrophages was significantly increased after interferon-γ stimulation. Conclusions.— Our findings suggest that plasma galectin-9 is a good biomarker for diagnosing advanced CKD.
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- 2022
6. TREM-2 mediates dendritic cell–induced NO to suppress Th17 activation and ameliorate chronic kidney diseases
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Ching-Cheng Lin, Ti-Yung Chang, Yong-Chen Lu, Yun-Syuan Wu, Wei Huang, Wei-Chi Lo, Guan-Fu Liu, Wei-Chan Hsu, Pamela S. Ohashi, Tak W. Mak, Jong-Ling Fuh, Hui-Chen Chen, Der-Cherng Tarng, and Nien-Jung Chen
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Lipopolysaccharides ,Membrane Glycoproteins ,Nephritis ,Dendritic Cells ,Arginine ,Nitric Oxide ,Mice ,Drug Discovery ,Animals ,Th17 Cells ,Molecular Medicine ,Receptors, Immunologic ,Renal Insufficiency, Chronic ,Genetics (clinical) ,Ureteral Obstruction - Abstract
Chronic kidney disease (CKD) is a global public health issue. CKD is caused by the infiltration of various myeloid cell types into renal tissue, resulting in renal fibrosis and tubular atrophy. Unilateral ureteral obstruction (UUO) surgery in mice is a model of CKD and characterized by high expression of the anti-inflammatory receptor, Triggering receptor expressed on myeloid cells 2 (TREM-2), on myeloid cells in affected kidneys. Here, we show that iNOS expression and nitric oxide (NO) induction were decreased in Trem-2
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- 2022
7. Prediction of the risk of developing end-stage renal diseases in newly diagnosed type 2 diabetes mellitus using artificial intelligence algorithms
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Shuo-Ming Ou, Ming-Tsun Tsai, Kuo-Hua Lee, Wei-Cheng Tseng, Chih-Yu Yang, Tz-Heng Chen, Pin-Jie Bin, Tzeng-Ji Chen, Yao-Ping Lin, Wayne Huey-Herng Sheu, Yuan-Chia Chu, and Der-Cherng Tarng
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Computational Mathematics ,Computational Theory and Mathematics ,Genetics ,Molecular Biology ,Biochemistry ,Computer Science Applications - Abstract
Objectives Type 2 diabetes mellitus (T2DM) imposes a great burden on healthcare systems, and these patients experience higher long-term risks for developing end-stage renal disease (ESRD). Managing diabetic nephropathy becomes more challenging when kidney function starts declining. Therefore, developing predictive models for the risk of developing ESRD in newly diagnosed T2DM patients may be helpful in clinical settings. Methods We established machine learning models constructed from a subset of clinical features collected from 53,477 newly diagnosed T2DM patients from January 2008 to December 2018 and then selected the best model. The cohort was divided, with 70% and 30% of patients randomly assigned to the training and testing sets, respectively. Results The discriminative ability of our machine learning models, including logistic regression, extra tree classifier, random forest, gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and light gradient boosting machine were evaluated across the cohort. XGBoost yielded the highest area under the receiver operating characteristic curve (AUC) of 0.953, followed by extra tree and GBDT, with AUC values of 0.952 and 0.938 on the testing dataset. The SHapley Additive explanation summary plot in the XGBoost model illustrated that the top five important features included baseline serum creatinine, mean serum creatine within 1 year before the diagnosis of T2DM, high-sensitivity C-reactive protein, spot urine protein-to-creatinine ratio and female gender. Conclusions Because our machine learning prediction models were based on routinely collected clinical features, they can be used as risk assessment tools for developing ESRD. By identifying high-risk patients, intervention strategies may be provided at an early stage.
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- 2023
8. Cover Image, Volume 71, Issue 4
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Yu‐Jie Huang, Chia‐Chi Hung, Pei‐Chien Hsu, Po‐Yi Lee, Yen‐An Tsai, Yu‐Chiao Hsin, Xie‐Ting Lee, Chia‐Cheng Chou, Mei‐Lien Chen, Der‐Cherng Tarng, and Yi‐Hsuan Lee
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Cellular and Molecular Neuroscience ,Neurology - Published
- 2023
9. Di-(2-ethylhexyl) Phthalate Limits the Lipid-Lowering Effects of Simvastatin by Promoting Protein Degradation of Low-Density Lipoprotein Receptor: Role of PPARγ-PCSK9 and LXRα-IDOL Signaling Pathways
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Bei-Chia Guo, Ko-Lin Kuo, Jenq-Wen Huang, Chia-Hui Chen, Der-Cherng Tarng, and Tzong-Shyuan Lee
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reactive oxygen species ,peroxisome proliferator-activated receptor γ ,Physiology ,Clinical Biochemistry ,liver X receptor α ,statin ,di-(2-ethylhexyl) phthalate ,Cell Biology ,Biochemistry ,transient receptor potential ankyrin 1 ,low-density lipoprotein receptor ,proprotein convertase subtilisin/kexin type 9 ,inducible degrader of the low-density lipoprotein receptor ,Molecular Biology - Abstract
Dialysis prevents death from uremia in patients with end-stage renal disease (ESRD). Nevertheless, during hemodialysis, circulating levels of di-(2-ethylhexyl) phthalate (DEHP) are increased due to phthalates leaching from medical tubes. Statins are an effective therapy for reducing the risks associated with cardiovascular diseases in patients with chronic kidney disease; however, the mechanism by which statins fail to reduce cardiovascular events in hemodialysis ESRD patients remains unclear. In this study, we investigated whether DEHP and its metabolites interfere with the lipid-lowering effect of statins in hepatocytes. In Huh7 cells, treatment with DEHP and its metabolites abolished the simvastatin-conferred lipid-lowering effect. Mechanistically, DEHP down-regulated the expression of low-density lipoprotein receptor (LDLR) and led to a decrease in LDL binding, which was mediated by the activation of the PPARγ-PCSK9 and LXRα-IDOL signaling pathways. Additionally, the NOX-ROS-TRPA1 pathway is involved in the DEHP-mediated inhibition of LDLR expression and LDL binding activity. Blockage of this pathway abrogated the DEHP-mediated inhibition in the LDLR expression and LDL binding of simvastatin. Collectively, DEHP induces the activation of the NOX-ROS-TRPA1 pathway, which in turn activates PPARγ-PCSK9- and LXRα-IDOL-dependent signaling, and, ultimately, diminishes the statin-mediated lipid-lowering effect in hepatocytes.
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- 2023
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10. Weight-Based Assessment of Access Flow Threshold to Predict Arteriovenous Fistula Functional Patency
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Yi-Fang Wang, Der-Cherng Tarng, Bo-Sheng Wu, Yan-Hwa Wu Lee, and Chih Yu Yang
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medicine.medical_specialty ,Flow (mathematics) ,Nephrology ,business.industry ,medicine ,Arteriovenous fistula ,Radiology ,medicine.disease ,business ,Weight based dosing - Abstract
The 2019 Kidney Disease Outcome Quality Initiative (K/DOQI) guideline recommended evaluating arteriovenous fistula (AVF) malfunction risks primarily based on clinical monitoring, which can be assisted with the value of vascular access flow (Qa). Nevertheless, Qa thresholds recommended by different guidelines vary, ranging from 300 to 500 ml/min. This study investigated the optimal Qa threshold to predict future functional patency in AVFs with Qa 500 ml/min.Both the clinical indicators of access dysfunction and the Qa value were monitored in patients receiving hemodialysis by the radiocephalic AVF. Routine access flow surveillance was performed by the ultrasound dilution method (HD03, Transonic Inc.). The development of clinically significant indicators of access dysfunction, which necessitated percutaneous transluminal angiography (PTA) to maintain functional patency, was analyzed in this cohort.Among the enrolled 302 patients, Qa of 52 patients was under 500 ml/min. These 52 patients received 2 Qa measurements during the follow-up period. Of these 52 patients, serial Qa of 17 patients varied trivially and their AVF remained functional. Multivariable logistic regression analysis revealed that a low Qa per ideal body weight (IBW) is an independent predictor of AVF functional loss. Receiver operating characteristic curve analysis of Qa/IBW in predicting future AVF functional loss revealed that the best cutoff value of Qa is 7.1 times the IBW.For radiocephalic AVFs with Qa 500 ml/min, the minimally required Qa to maintain access function is associated with individual IBW. The IBW-based Qa threshold assessment would allow more flexibility in the treatment of patients and reduce unnecessary invasive measures.
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- 2022
11. Mortality rate of end-stage kidney disease patients in Taiwan
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Bo-Sheng Wu, Chia-Ling Helen Wei, Chih-Yu Yang, Ming-Huang Lin, Chih-Cheng Hsu, Yu-Juei Hsu, Shih-Hua Lin, and Der-Cherng Tarng
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Survival Rate ,Renal Dialysis ,Taiwan ,Humans ,Kidney Failure, Chronic ,General Medicine ,Retrospective Studies - Abstract
End-stage kidney disease (ESKD) is a global burden that reflects each country's unique condition. We used the National Health Insurance Research Database (NHIRD) of Taiwan to decipher changes in the mortality and international survival rates and to determine the effectiveness of the pre-end-stage renal disease care program (pre-ESRD care program) to guide future health policies for ESKD.We conducted a retrospective cohort analysis of the NHIRD data along with records from the catastrophic illness certificate program of ESKD patients from 2010 to 2018.From 2010 to 2018, the annual dialysis-related mortality rate in Taiwan increased from 10.6 to 11.8 deaths per hundred patient-years. The mortality rate for patients below 40 years appears to be decreasing, reflecting the improved quality of care for ESKD patients. Patients above 75 years showed increasing mortality, indicating the prolonged survival and aging of the ESKD population. Patients undergoing dialysis who participated in the pre-ESRD care program had a higher post-dialysis initiation life expectancy than those who did not participate. Among the program enrollees, the post-dialysis initiation life expectancy was higher in patients who had participated for more than one year. Taiwan has one of the highest ESKD patient survival rates globally.From 2010 to 2018, the reduced mortality in young patients and aging of the ESKD population might indicate that the quality of care in Taiwan for ESKD has improved. Furthermore, a better survival rate after dialysis initiation was observed in the pre-ESRD care program participants.
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- 2022
12. Association of anemia and iron parameters with mortality among prevalent peritoneal dialysis patients in Taiwan: the AIM-PD study
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Ko-Lin Kuo, Jia-Sin Liu, Ming-Huang Lin, Chih-Cheng Hsu, Der-Cherng Tarng, and the Taiwan Society of Nephrology Renal Registry Data System Research Group
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Science ,Medicine - Abstract
In 1996, the National Health Insurance Administration of Taiwan applied a restrictive reimbursement criteria for erythropoiesis-stimulating agents (ESAs) use in patients with chronic kidney disease. The maximal ESAs dosage allowed by insurance is capped at 20,000 U of epoetin per month. Nephrologists avoided the use of high ESA dosages to achieve a hemoglobin level of 10–11 g/dL using iron supplementation. We assessed the association of anemia and iron parameters with mortality among peritoneal dialysis (AIM-PD) patients. A retrospective cohort study was conducted based on the Taiwan Renal Registry Data System. From January 1, 2000 to December 31, 2008, we enrolled 4356 well-nourished PD patients who were older than 20 years and had been receiving PD for more than 12 months. All patients were divided into subgroups according to different hemoglobin, ferritin and transferrin saturation (TSAT) values. Patients were followed until death or December 31, 2008. In a median 2.9-year study period, 694 (15.9%) patients died. By multivariate adjustment, a hemoglobin level lower than 10 g/dL was significantly associated with a higher risk for all-cause and cardiovascular deaths. Moreover, a serum ferritin level higher than 800 ng/mL was associated with a higher risk for all-cause deaths, and a TSAT value between 20 and 50% was associated with the lowest all-cause mortality. In conclusions, we recommend avoiding a low hemoglobin level and a serum ferritin level of more than 800 ng/mL and maintaining a TSAT value between 20 and 50%, as these conditions were associated with lower risks of all-cause mortality in the AIM-PD study.
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- 2022
13. Pentraxin 3 Predicts Arteriovenous Fistula Functional Patency Loss and Mortality in Chronic Hemodialysis Patients
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Heng-Cheng Tsai, Shuo-Ming Ou, Chih-Cheng Wu, Chin-Chou Huang, Jyh-Tong Hsieh, Po-Yu Tseng, Chiu-Yang Lee, Chih-Yu Yang, and Der-Cherng Tarng
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Aged, 80 and over ,Male ,Middle Aged ,Serum Amyloid P-Component ,Arteriovenous Shunt, Surgical ,C-Reactive Protein ,Renal Dialysis ,Risk Factors ,Nephrology ,Arteriovenous Fistula ,Humans ,Kidney Failure, Chronic ,Prospective Studies ,Vascular Patency ,Aged ,Retrospective Studies - Abstract
Introduction: Viable vascular access is the lifeline for hemodialysis patients. In the nondialysis population, emerging evidence suggests that circulating pentraxin 3 (PTX3), neutrophil gelatinase-associated lipocalin (NGAL), and chitinase-3-like protein 1 (CHI3L1) are associated with cardiovascular inflammation and endothelial injury. However, predictive values of these three biomarkers on arteriovenous fistula (AVF) outcomes are unknown. Methods: This prospective observational cohort study enrolled 135 hemodialysis patients using AVF and then followed them for 3 years. Plasma levels of PTX3, NGAL, and CHI3L1 were measured. Patients were followed up prospectively for two clinical outcomes, including AVF functional patency loss and death. Cox proportional hazards regression models were used to analyze hazard ratios for the commencement of AVF functional patency loss and mortality. Results: Among 135 patients, the mean age was 66.0 ± 15.7 years old and 48.1% were male. The plasma level of PTX3, NGAL, and CHI3L1 was 2.8 ± 2.3 ng/mL, 349.2 ± 111.4 ng/mL, and 185.5 ± 66.8 ng/mL, respectively. During a 3-year follow-up period, the plasma level of PTX3 was an independent predictor for AVF functional patency loss (per 1 ng/mL increase, HR 1.112 [95% CI: 1.001–1.235], p = 0.048). Besides, patients with higher plasma levels of PTX3 were more likely to suffer from cardiovascular mortality (per 1 ng/mL increase, HR 1.320 [95% CI: 1.023–1.703], p = 0.033), infectious mortality (per 1 ng/mL increase, HR 1.394 [95% CI: 1.099–1.769], p = 0.006), and all-cause mortality (per 1 ng/mL increase, HR 1.233 [95% CI: 1.031–1.476], p = 0.022). Conclusions: The plasma level of PTX3, not NGAL or CHI3L1, was associated with higher risks of AVF functional patency loss in chronic hemodialysis patients, showing its value in reflecting AVF endothelial dysfunction. Furthermore, PTX3 also predicts mortality in chronic hemodialysis patients.
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- 2022
14. Astrocytic aryl hydrocarbon receptor mediates chronic kidney disease-associated mental disorders involving GLT1 hypofunction and neuronal activity enhancement in the mouse brain
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Yu‐Jie Huang, Chia‐Chi Hung, Pei‐Chien Hsu, Po‐Yi Lee, Yen‐An Tsai, Yu‐Chiao Hsin, Xie‐Ting Lee, Chia‐Cheng Chou, Mei‐Lien Chen, Der‐Cherng Tarng, and Yi‐Hsuan Lee
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Cellular and Molecular Neuroscience ,Neurology - Abstract
Chronic kidney disease (CKD)-associated mental disorders have been attributed to the excessive accumulation of hemodialysis-resistant indoxyl-3-sulfate (I3S) in the brain. I3S not only induces oxidative stress but is also a potent endogenous agonist of the aryl hydrocarbon receptor (AhR). Here, we investigated the role of AhR in CKD-induced brain disorders using a 5/6 nephrectomy-induced CKD mouse model, which showed increased I3S concentration in both blood and brain, anxiety and impaired novelty recognition, and AhR activation in the anterior cortex. GFAP
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- 2022
15. UMOD Mutations in Chronic Kidney Disease in Taiwan
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Huan-Da Chen, Chih-Chuan Yu, I-Hsiao Yang, Chi-Chih Hung, Mei-Chuan Kuo, Der-Cherng Tarng, Jer-Ming Chang, and Daw-Yang Hwang
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Medicine (miscellaneous) ,General Biochemistry, Genetics and Molecular Biology ,uromodulin ,chronic kidney disease (CKD) ,autosomal dominant tubulointerstitial kidney disease (ADTKD) ,kidney failure (KF) - Abstract
UMOD is the first identified and the most commonly mutated gene that causes autosomal dominant tubulointerstitial kidney disease (ADTKD). Recent studies have shown that ADTKD-UMOD is a relatively common cause of chronic kidney disease (CKD). However, the status of ADTKD-UMOD in Taiwan remains unknown. In this study, we identified three heterozygous UMOD missense variants, c.121T > C (p.Cys41Arg), c.179G > A (p.Gly60Asp), and c.817G > T (p.Val273Phe), in a total of 221 selected CKD families (1.36%). Two of these missense variants, p.Cys41Arg and p.Gly60Asp, have not been reported previously. In vitro studies showed that both uromodulin variants have defects in cell membrane trafficking and excretion to the culture medium. The structure model predicted altered disulfide bond formation in both variants, but only p.Gly60Asp was predicted to cause protein destabilization. Our findings extend the mutation spectrum and indicate that the ADTKD-UMOD contributed to a small but significant cause of CKD in the Taiwanese population.
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- 2022
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16. Associations of atrial fibrillation with renal function decline in patients with chronic kidney disease
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Der Cherng Tarng, Tz Heng Chen, Yuan Chia Chu, and Shuo Ming Ou
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Male ,medicine.medical_specialty ,030232 urology & nephrology ,Renal function ,Disease ,030204 cardiovascular system & hematology ,Kidney ,urologic and male genital diseases ,Egfr decline ,Risk Assessment ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Atrial Fibrillation ,Humans ,Medicine ,In patient ,Renal Insufficiency, Chronic ,Retrospective Studies ,business.industry ,Atrial fibrillation ,medicine.disease ,Propensity score matching ,Kidney Failure, Chronic ,Female ,Cardiology and Cardiovascular Medicine ,business ,Cohort study ,Kidney disease - Abstract
BackgroundChronic kidney disease (CKD) is known to increase the risk of atrial fibrillation (AF) development, but the relationship between AF and subsequent renal function decline in patients with CKD is not well understood. In this study, we explored the role of AF on renal outcomes among patients with CKD.MethodsIn a retrospective hospital-based cohort study, we identified patients with CKD aged ≥20 years from 1 January 2008 to 31 December 2018. The patients were divided into AF and non-AF groups. We matched each patient with CKD and AF to two non-AF CKD controls according to propensity scores. The outcomes of interest included estimated glomerular filtration rate (eGFR) decline of ≥20%, ≥30%, ≥40% and ≥50%, and end-stage renal disease (ESRD).ResultsAfter propensity score matching, 6731 patients with AF and 13 462 matched controls were included in the analyses. Compared with the non-AF group, the AF group exhibited greater risks of eGFR decline ≥20% (HR 1.43; 95% CI 1.33 to 1.53), ≥30% (HR 1.50; 95% CI 1.36 to 1.66), ≥40% (HR 1.62; 95% CI 1.41 to 1.85) and ≥50% (HR 1.82; 95% CI 1.50 to 2.20), and ESRD (HR 1.22; 95% CI 1.12 to 1.34). Higher CHA2DS2-VASc scores were associated with greater risks of eGFR decline and ESRD.ConclusionsIn patients with CKD, AF was associated with greater risks of subsequent renal function decline. CHA2DS2-VASc scores may be a useful risk stratification scheme for predicting the risk of renal function decline.
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- 2021
17. Decoy Receptor 3 Suppresses T-Cell Priming and Promotes Apoptosis of Effector T-Cells in Acute Cell-Mediated Rejection: The Role of Reverse Signaling
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Shuo-Chun, Weng, Mei-Chin, Wen, Shie-Liang, Hsieh, Nien-Jung, Chen, and Der-Cherng, Tarng
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Male ,Mice, Inbred C57BL ,Caspase 8 ,Mice ,Receptors, Tumor Necrosis Factor, Type I ,Receptors, Tumor Necrosis Factor, Member 6b ,Immunology ,Animals ,Immunology and Allergy ,Apoptosis ,Female ,CD8-Positive T-Lymphocytes ,Receptors, Tumor Necrosis Factor - Abstract
BackgroundDecoy receptor 3 (DcR3) belongs to the tumor necrosis factor (TNF) receptor superfamily and neutralizes TNF ligands, including FasL and TRAIL, to prevent T activation during T-cell priming. However, the cellular mechanisms underlying acute cell-mediated rejection (ACMR) remain unknown.MethodsWe generated DcR3 transgenic (Tg) mice and mice with high DcR3 expression (HDE) to study both in vivo and in vitro. FasR RNA knockdown in immortalized CD4+CD8+ T-cells was used to survey the role of DcR3 on FasR/Fas-associated protein with death domain (FADD)/caspase 8 pathway and its cross-link to TNF receptor-associated factor 1 (TNFR1)-associated death domain protein (TRADD) in suppressing TNFR1. TNF/TRADD knockout mice were used to show the importance of TNF adaptor protein.ResultsDcR3.Fc suppressed C57BL/6 female T-cell activation and transformation into CD4+CD69+, CD4+CD44+, and CD4+CD25+Foxp3+ when compared with isotype IgG1 and its co-treatment with FasL/TRAIL after exposing to bone marrow-derived dendritic cells (BMDCs) that carried alloantigen with male H-Y and minor antigenic determinant. Interleukin-17 and interferon-γ productions by BMDC-activated T-cells were lowered after co-treating with DcR3.Fc. DcR3.Fc induced effector T-cells (Teffs) and was susceptible to FasR-mediated apoptosis through the FADD/TRADD/caspase 8 pathway. After exposing to DcR3.Fc, TRADD was silenced, likely turning down the inflammatory response. The systemic effects of DcR3 Tg mice and HDE phenotype induced by the promoter of cytomegalovirus not only attenuated ACMR severity but also ameliorated the high serum creatinine and blood urea nitrogen levels even with high T-cell exposure frequencies. Besides this, DcR3 has minor biological effects on both MHC-matched and MHC-mismatched models.ConclusionsHigh DcR3 doses protect renal tubular epithelial cells from acute T-cell attack during the T-cell priming stage via interfering with TNF ligand-mediated reverse signaling and possibly promoting Teff apoptosis through FasR upregulation. Our findings supported that the decoy receptor is involved in T-cell modulation in kidney transplant rejection.
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- 2022
18. IgM mesangial deposition as a risk factor for relapses of adult-onset minimal change disease
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Chih Yu Yang, Der Cherng Tarng, Fan Yu Chen, An Hang Yang, Fu Pang Chang, Yang Ho, Bo Sheng Wu, and Cheng Wen Yang
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Nephrology ,Adult ,Male ,medicine.medical_specialty ,030232 urology & nephrology ,Statistical difference ,lcsh:RC870-923 ,Gastroenterology ,Cohort Studies ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Recurrence ,Risk Factors ,Internal medicine ,medicine ,Humans ,Minimal change disease ,Risk factor ,Relapse ,Retrospective Studies ,Kidney ,biology ,business.industry ,Nephrosis, Lipoid ,Retrospective cohort study ,IgM mesangial deposition ,Middle Aged ,medicine.disease ,lcsh:Diseases of the genitourinary system. Urology ,Adult-onset ,Glomerular Mesangium ,medicine.anatomical_structure ,Immunoglobulin M ,030220 oncology & carcinogenesis ,biology.protein ,Female ,business ,Deposition (chemistry) ,Research Article - Abstract
BackgroundImmunoglobulin M (IgM) mesangial deposition in pediatric minimal change disease (MCD) has been reported to be associated with steroid dependence and poor renal outcomes. However, the evidence linking the impacts of IgM mesangial deposition to the treatment prognosis in adult-onset MCD is still elusive.MethodsIn this retrospective cohort study, 37 adult patients with MCD received kidney biopsies from January 2010 to May 2020. Immunofluorescence microscopy was performed and the patients dichotomized according to IgM mesangial deposition (12 patients with positive IgM deposition; 25 patients with negative IgM deposition). We analyzed the clinical features, the dosage of immunosuppressive agents, and the response to treatment for 2 years between the two groups.ResultsAnalysis of the clinical symptoms, the dosage of immunosuppressive treatment, and the time to remission revealed no statistical difference between the groups. However, compared to the negative IgM group, the frequency of relapses was significantly higher in the positive IgM group during the two-year follow-up period (the negative IgM group 0.25 episodes/year; the positive IgM group 0.75 episodes/year,p = 0.029). Furthermore, multivariate linear regression revealed that the positivity of IgM mesangial deposition is independently associated with the frequency of relapses (regression coefficient B 0.450, 95% CI 0.116–0.784,p = 0.010).ConclusionsOur findings indicated that adult-onset MCD patients with IgM mesangial deposition have a high risk of relapses. Therefore, intensive monitoring of disease activity should be considered in MCD adults with IgM mesangial deposition.
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- 2021
19. Circadian rhythm dynamics on multiscale entropy identifies autonomic dysfunction associated with risk of ventricular arrhythmias and near syncope in chronic kidney disease
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Yenn Jiang Lin, Men Tzung Lo, Shih Lin Chang, Shih Ann Chen, Tsung Ying Tsai, Shin Huei Liu, Der Cherng Tarng, Tze Fan Chao, Jo Nan Liao, Wen Han Cheng, Li Wei Lo, Fa Po Chung, and Yu Feng Hu
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Male ,medicine.medical_specialty ,Entropy ,030204 cardiovascular system & hematology ,Syncope ,Sudden cardiac death ,Multiscale entropy ,03 medical and health sciences ,0302 clinical medicine ,Heart Rate ,Risk Factors ,Internal medicine ,medicine ,Humans ,Heart rate variability ,030212 general & internal medicine ,Circadian rhythm ,Renal Insufficiency, Chronic ,Aged ,Retrospective Studies ,Aged, 80 and over ,biology ,business.industry ,Syncope (genus) ,Arrhythmias, Cardiac ,Retrospective cohort study ,Middle Aged ,medicine.disease ,biology.organism_classification ,Circadian Rhythm ,Autonomic nervous system ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Kidney disease - Abstract
Background A discordant biological clock could potentially induce sudden cardiac death (SCD). We aimed to evaluate the circadian change of heart rate variability (HRV) and its relationship to the risks of ventricular arrhythmia (VA) and near syncope in patients with chronic kidney disease (CKD). Methods In this retrospective study, non-CKD and CKD patients were enrolled and underwent a 24-hour Holter examination for linear and nonlinear HRV analyses. The multiscale entropy (MSE) method was selected for nonlinear HRV analyses. The documented VAs or episodes of near syncope were classified as high-risk SCD group (n = 8) and others as low-risk SCD group (n = 21). Results In linear analyses, time and frequency domains revealed no significant difference between groups. In nonlinear analyses with MSE, MSE5, MSE6–20, and MSEslope 5 were significantly lower (p = 0.002, p Conclusions Nonlinear analysis with MSE demonstrated the loss of circadian change in CKD patients and was associated with a higher risk for VAs and near syncope. The MSE method demonstrated the diurnal change of rhythm dynamics which identifies potential autonomic dysfunction leading to poor prognosis.
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- 2020
20. Flumazenil partially reverses gamma-hydroxybutyrate (GHB)-induced coma: a case report
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Shiao-Yu Chen, Feng-Yuan Chu, Chih-Yu Yang, and Der-Cherng Tarng
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Flumazenil ,Baclofen ,Psychiatry and Mental health ,Clinical Psychology ,Humans ,Medicine (miscellaneous) ,Coma ,Sodium Oxybate - Published
- 2022
21. Artificial Intelligence for Risk Prediction of End-Stage Renal Disease in Sepsis Survivors with Chronic Kidney Disease
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Kuo-Hua Lee, Yuan-Chia Chu, Ming-Tsun Tsai, Wei-Cheng Tseng, Yao-Ping Lin, Shuo-Ming Ou, and Der-Cherng Tarng
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Medicine (miscellaneous) ,sepsis ,chronic kidney disease ,machine learning ,artificial intelligence ,end-stage renal disease ,urologic and male genital diseases ,General Biochemistry, Genetics and Molecular Biology ,female genital diseases and pregnancy complications - Abstract
Sepsis may lead to kidney function decline in patients with chronic kidney disease (CKD), and the deleterious effect may persist in patients who survive sepsis. We used a machine learning approach to predict the risk of end-stage renal disease (ESRD) in sepsis survivors. A total of 11,661 sepsis survivors were identified from a single-center database of 112,628 CKD patients between 2010 and 2018. During a median follow-up of 3.5 years, a total of 1366 (11.7%) sepsis survivors developed ESRD after hospital discharge. We adopted the random forest, extra trees, extreme gradient boosting, light gradient boosting machine (LGBM), and gradient boosting decision tree (GBDT) algorithms to predict the risk of ESRD development among these patients. GBDT yielded the highest area under the receiver operating characteristic curve of 0.879, followed by LGBM (0.868), and extra trees (0.865). The GBDT model revealed the strong effect of estimated glomerular filtration rates
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- 2022
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22. Baseline Peritoneal Membrane Transport Characteristics Are Associated with Peritonitis Risk in Incident Peritoneal Dialysis Patients
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Yi-Hsin Chou, Yung-Tai Chen, Jinn-Yang Chen, Der-Cherng Tarng, Chih-Ching Lin, and Szu-Yuan Li
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Process Chemistry and Technology ,peritoneal dialysis ,peritonitis ,peritoneal equilibration test ,Chemical Engineering (miscellaneous) ,Filtration and Separation - Abstract
The peritoneal equilibration test (PET) is a semi-quantitative measurement that characterizes the rate of transfer of solutes and the water transfer rate across the peritoneum in patients treated with peritoneal dialysis (PD). The results of the PET are used to maximize daily peritoneal ultrafiltration and solute clearances. Previous studies have shown that high transport status is associated with ultrafiltration failure, malnutrition, and reduced survival; however, the way in which peritoneum transport characteristics affect peritonitis risk is unknown. In the current cohort study, we recruited 898 incident-PD patients and used intention-to-treat analysis to test if baseline PET affected the subsequent 3-year peritonitis rate. Among all recruited PD patients, 308 (34.2%) developed peritonitis within three years. Multivariate Cox regression analysis showed that the high-transport group has the greatest peritonitis risk (HR 1.98, 95% CI: 1.08–3.62) even after an adjustment for demographics, comorbid diseases, and biochemical measurements. We concluded that a baseline high peritoneal membrane transport rate is an independent risk factor for peritonitis in incident PD patients.
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- 2022
23. Urinary Galectin-3 as a Novel Biomarker for the Prediction of Renal Fibrosis and Kidney Disease Progression
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Shuo-Ming Ou, Ming-Tsun Tsai, Huan-Yuan Chen, Fu-An Li, Kuo-Hua Lee, Wei-Cheng Tseng, Fu-Pang Chang, Yao-Ping Lin, Ruey-Bing Yang, and Der-Cherng Tarng
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galectin-3 ,kidney disease progression ,renal biopsy ,renal fibrosis ,urinary biomarkers ,Medicine (miscellaneous) ,General Biochemistry, Genetics and Molecular Biology - Abstract
Plasma galectin-3 (Gal-3) is associated with organ fibrosis, but whether urinary Gal-3 is a potential biomarker of kidney disease progression has never been explored. Between 2018 and 2021, we prospectively enrolled 280 patients who underwent renal biopsy and were divided into three groups based on their urinary Gal-3 levels (
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- 2022
24. Factors affecting arteriovenous access patency after percutaneous transluminal angioplasty in chronic haemodialysis patients under vascular access monitoring and surveillance: a single-centre observational study
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Chung-Kuan Wu, Der-Cherng Tarng, Chih-Yu Yang, Jyh-Gang Leu, and Chia-Hsun Lin
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Angioplasty ,Graft Occlusion, Vascular ,nephrology ,General Medicine ,vascular medicine ,urologic and male genital diseases ,vascular surgery ,body regions ,Arteriovenous Shunt, Surgical ,Treatment Outcome ,Renal Dialysis ,otorhinolaryngologic diseases ,Medicine ,Humans ,dialysis ,Surgery ,Angioplasty, Balloon ,Retrospective Studies - Abstract
ObjectivesMaintenance of vascular access (VA) patency after percutaneous transluminal angioplasty (PTA) is important and remains a challenge despite VA monitoring and surveillance. The aim of this study was to examine factors affecting the post-PTA arteriovenous access (AVA) patency in patients who have been on close VA monitoring and surveillance for access flow.DesignRetrospective cohort study.SettingA single medical centre in Taiwan.ParticipantsRecords of patients who received chronic haemodialysis between 1 January 2017 and 31 December 2018 were retrospectively reviewed. Patients were divided into two groups (without or with PTA intervention on AVA).Primary and secondary outcomePatients were followed until reintervention PTA, termination or abandoned VA or end of study. In addition to routine monitoring, VA flow surveillance was performed every 3 months for detection of VA dysfunction adhering to Kidney Disease Outcomes Quality Initiative guidelines.ResultsA total of 508 patients were selected for study inclusion (with PTA, n=231; without PTA, n=277). At baseline, variables that differed between groups included malignancy and levels of albumin, uric acid, potassium, phosphorous, high-density lipoprotein, total bilirubin and ferritin (all pConclusionsAVG access type, acute myocardial infarction, and high ferritin levels are risk factors for re-intervention post-PTA. These findings may be useful in the development of prophylactic strategies for monitoring VA function and tailoring surveillance programs for these dialysis patients.
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- 2022
25. Effect of Renin-Angiotensin-Aldosterone System Blockade on Long-Term Outcomes in Postacute Kidney Injury Patients With Hypertension*
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Yao Ping Lin, Der Cherng Tarng, Chih Yu Yang, Ming Huang Lin, Jia Sin Liu, Ming Tsun Tsai, Zih Kai Kao, Chih Cheng Hsu, and Wei Cheng Tseng
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Adult ,Male ,medicine.medical_specialty ,Angiotensin receptor ,medicine.medical_treatment ,Angiotensin-Converting Enzyme Inhibitors ,Critical Care and Intensive Care Medicine ,Renin-Angiotensin System ,Angiotensin Receptor Antagonists ,Young Adult ,Internal medicine ,Renin–angiotensin system ,medicine ,Humans ,Renal replacement therapy ,Dialysis ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Hazard ratio ,Acute kidney injury ,Retrospective cohort study ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,Blockade ,Treatment Outcome ,Hypertension ,Female ,business - Abstract
Objectives Renal replacement therapy-requiring acute kidney injury frequently occurs in ICUs, which require evidence-based medical attention. However, in the postacute kidney injury patient population, the evidence regarding effective therapies to improve patient outcomes is lacking. Therefore, we aimed to examine whether the renin-angiotensin-aldosterone system blockade is effective in improving renal outcomes in postacute kidney injury patients who experienced temporary renal replacement therapy and have hypertension. Design A retrospective cohort study. Setting A nationwide database in Taiwan. Patients From January 1, 2000, to December 31, 2013, we identified 8,558 acute kidney injury patients with hypertension in the national registry database. All these patients experienced an acute kidney injury episode, which required temporary renal replacement therapy for at least once. Interventions Users (n = 3,885) and nonusers (n = 4,673) of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Measurements and main results We used Cox proportional hazards regression models to analyze hazard ratios for the commencement of end-stage renal disease and all-cause mortality for angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users (n = 3,885) and nonusers (n = 4,673). In a median follow-up of 4.3 years, 5,880 patients (68.7%) required long-term dialysis, and 4,841 patients (56.6%) died. Compared with postacute kidney injury patients who did not use angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users are marginally less likely to progress to end-stage renal disease (adjusted hazard ratio 0.95; 95% CI 0.90-1.01; p = 0.06) and significantly less likely to suffer from all-cause mortality (adjusted hazard ratio 0.93; 95% CI 0.87-0.98; p = 0.011). Conclusions In patients who experienced renal replacement therapy-requiring acute kidney injury and have hypertension, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use is associated with better survival outcomes compared with nonuser.
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- 2020
26. Hemodialysis vascular access care during the COVID-19 pandemic
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Yi Fang Wang, Yang Ho, Chiu Yang Lee, Cheng Hsueh Wu, Der Cherng Tarng, and Chih Yu Yang
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medicine.medical_specialty ,medicine.medical_treatment ,Pneumonia, Viral ,MEDLINE ,Infection control ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Betacoronavirus ,0302 clinical medicine ,Renal Dialysis ,Pandemic ,medicine ,Severe acute respiratory syndrome coronavirus 2 ,Humans ,Review Articles ,Pandemics ,Dialysis ,Quality of Health Care ,Hemodialysis vascular access ,business.industry ,SARS-CoV-2 ,Incidence (epidemiology) ,COVID-19 ,General Medicine ,medicine.disease ,Pneumonia ,030220 oncology & carcinogenesis ,Emergency medicine ,Hemodialysis ,business ,Coronavirus Infections ,Vascular Access Devices ,Kidney disease - Abstract
Dialysis patients are more vulnerable and susceptible to the severe coronavirus disease 2019 (COVID-19) infection due to multiple comorbidities. Since Taiwan has the highest incidence and prevalence of treated end-stage kidney disease worldwide, it is crucial to act in advance to prevent a potential disaster. In the face of the COVID-19 pandemic, we implement proactive infection control measures to prevent it from spreading without sacrificing the dialysis care quality. In this article, we focused on hemodialysis vascular access (HVA) care in particular. As a life-line of hemodialysis (HD) patients, HVA care has a profound impact on the patient's quality of dialysis and life. Specifically, in our facility, the working and office areas of the HD units are separated to reduce cross-infection. All elective procedures for HVA are postponed, and operating rooms equipped with a negative-pressure anteroom are used for the suspected or confirmed COVID-19 patients. Herein, we share how we modified our HVA care policy not only to prevent our patients from COVID-19 infection but also to maintain the quality of HVA care.
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- 2020
27. Tubular transcriptional co-activator with PDZ-binding motif protects against ischemic acute kidney injury
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Alexander Charng Dar Tsai, Chung Ho Chang, Jui Lin Wang, Chia-Lin Wu, Tao Hsiang Yang, Chia Chu Chang, and Der Cherng Tarng
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Male ,0301 basic medicine ,p38 mitogen-activated protein kinases ,Renal cortex ,Apoptosis ,IκB kinase ,urologic and male genital diseases ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Humans ,Adaptor Proteins, Signal Transducing ,Kidney ,urogenital system ,Chemistry ,Kinase ,NF-kappa B ,Acute kidney injury ,Epithelial Cells ,General Medicine ,Acute Kidney Injury ,medicine.disease ,Mice, Inbred C57BL ,Kidney Tubules ,030104 developmental biology ,medicine.anatomical_structure ,Reperfusion Injury ,030220 oncology & carcinogenesis ,Trans-Activators ,Cancer research ,Female ,Signal transduction ,Signal Transduction - Abstract
Transcriptional co-activator with PDZ-binding motif (TAZ) is a key downstream effector of the Hippo tumor-suppressor pathway. The functions of TAZ in the kidney, especially in tubular epithelial cells, are not well-known. To elucidate the adaptive expression, protective effects on kidney injury, and signaling pathways of TAZ in response to acute kidney injury (AKI), we used in vitro (hypoxia-treated human renal proximal tubular epithelial cells [RPTECs]) and in vivo (mouse ischemia–reperfusion injury [IRI]) models of ischemic AKI. After ischemic AKI, TAZ was up-regulated in RPTECs and the renal cortex or tubules. Up-regulation of TAZ in RPTECs subjected to hypoxia was controlled by IκB kinase (IKK)/nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB) signaling. TAZ overexpression attenuated hypoxic and oxidative injury, inhibited apoptosis and activation of p38 and c-Jun N-terminal kinase (JNK) proteins, and promoted wound healing in an RPTEC monolayer. However, TAZ knockdown aggravated hypoxic injury, apoptosis, and activation of p38 and JNK signaling, delayed wound closure of an RPTEC monolayer, and promoted G0/G1 phase cell-cycle arrest. Chloroquine and verteporfin treatment produced similar results to TAZ overexpression and knockdown in RPTECs, respectively. Compared with vehicle-treated mice, chloroquine treatment increased TAZ in the renal cortex and tubules, improved renal function, and attenuated tubular injury and tubular apoptosis after renal IRI, whereas TAZ siRNA and verteporfin decreased TAZ in the renal cortex and tubules, deteriorated renal failure and tubular injury, and aggravated tubular apoptosis. Our findings indicate the renoprotective role of tubular TAZ in ischemic AKI. Drugs augmenting (e.g., chloroquine) or suppressing (e.g., verteporfin) TAZ in the kidney might be beneficial or deleterious to patients with AKI.
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- 2020
28. Impact of the COVID-19 pandemic on the management of patients with end-stage renal disease
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Der Cherng Tarng, Yu Jiun Chan, Yu Shuo Tang, and Szu Yuan Li
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Risk of infection ,General Medicine ,Disease ,030204 cardiovascular system & hematology ,Peritoneal dialysis ,End stage renal disease ,03 medical and health sciences ,0302 clinical medicine ,Personal hygiene ,Infectious disease (medical specialty) ,030220 oncology & carcinogenesis ,Pandemic ,medicine ,Hemodialysis ,Intensive care medicine ,business - Abstract
A novel infectious disease, coronavirus disease-2019 (COVID-19), spread globally since December 2019. Without effective treatment and vaccination, the strategies to restrain this disease are only keeping social distance, maintaining personal hygiene, quarantine, and isolation. However, thrice-a-week treatment is inevitable for all hemodialysis patients. In addition to the high risk of cluster infection and compromised immunity in patients with end-stage renal disease (ESRD), an atypical disease presentation could also make the medial system neglect these patients during CVOID-19 pandemic. To avoid COVID-19 transmission among patients on dialysis, the major societies of nephrology around the world have provided their guidelines for screening, dialysis facilities adjustment, and health education, respectively. In this review, we summarized the main contents and differences of these guidelines and addressed the prompt management for patients with ESRD to reduce the risk of infection during COVID-19 pandemic.
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- 2020
29. Anemia in patients of diabetic kidney disease
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Shang Feng Tsai and Der Cherng Tarng
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medicine.medical_specialty ,Anemia ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Diabetic Nephropathies ,Renal Insufficiency, Chronic ,Risk factor ,Erythropoietin ,business.industry ,General Medicine ,medicine.disease ,030220 oncology & carcinogenesis ,Erythropoiesis ,Animal studies ,Hemoglobin ,business ,Kidney disease ,medicine.drug - Abstract
Anemia is the major complication resulting from chronic kidney disease (CKD) and also a risk factor for cardiovascular events and a poor quality of life (QoL). Diabetic kidney disease (DKD) is the major cause of CKD. Initially, insulin resistance has been reported to increase erythropoiesis, but it might be a minor issue. DKD-related anemia developed earlier and was more severe than non-DKD-related anemia based on more complicated mechanisms, including greater bleeding tendency associated with antiplatelet effect, less O2 sensing due to autonomic neuropathy or renin-angiotensin-aldosterone system inhibitor use, inhibitory effect of inflammatory cytokines, urinary loss of erythropoietin (EPO), and poor response to EPO. In DKD patients, prompt correction of anemia allows for a better cardiovascular outcome and QoL, which are similar to the promising effect of anemia correction in CKD patients. However, current evidence recommended that the avoidance of a high or normalized hemoglobin (Hb) level has been suggested in the treatment of anemia in DKD patients. Despite that EPO has a pleotropic effect on renal protection from animal studies, the renal benefit was less evident in CKD and DKD patients. Recently, the antidiabetic agent, sodium glucose cotransporter-2 inhibitors (SGLT2i), has been reported to exhibit the renal benefits due to the tubulo-glomerular feedback in addition to sugar control. It may also be due to less renal ischemic through higher EPO levels, followed by higher Hb levels. More studies are needed to clarify the link between the renal benefit of SGLT2i and EPO production.
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- 2019
30. Associations of high anti-CMV IgG titer with renal function decline and allograft rejection in kidney transplant patients
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Tz-Heng Chen, Shuo-Ming Ou, and Der-Cherng Tarng
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Adult ,Male ,Graft Survival ,Cytomegalovirus ,General Medicine ,Middle Aged ,Antiviral Agents ,Kidney Transplantation ,Transplant Recipients ,Cohort Studies ,Immunoglobulin G ,Cytomegalovirus Infections ,Humans ,Immunologic Factors ,Renal Insufficiency ,Aged ,Retrospective Studies - Abstract
An anti-cytomegalovirus (CMV) immunoglobulin G (IgG) antibody is produced after primary CMV infection and generally persists after the primary infection. However, it is not well-known about the relationship between anti-CMV IgG titer and outcomes in kidney transplant recipients. We, therefore, aimed to explore the role of anti-CMV IgG titer on the risks of CMV disease development, allograft rejection, renal function decline, and mortality.In a hospital-based study, we identified 179 CMV-seropositive kidney transplant recipients between January 2013 and December 2017. These patients were divided into low and high anti-CMV IgG titer groups, respectively. The cutoff level of anti-CMV IgG titer was determined by receiver operating characteristic curve analysis. The outcomes evaluated included CMV disease, decrease of ≥15% in estimated glomerular filtration rate (eGFR), biopsy-proven allograft rejection, and all-cause mortality.The high anti-CMV IgG titer group (≥846.2 AU/mL) exhibited a higher risk of CMV disease (adjusted hazard ratio [aHR], 3.77; 95% CI, 1.47-9.68; p = 0.006), eGFR decline ≥15% (aHR, 2.00; 95% CI, 1.19-3.35; p = 0.009), and renal allograft rejection (aHR, 2.95; 95% CI, 1.11-7.87; p = 0.030) than the low titer group (846.2 AU/mL).In kidney transplant recipients, a high anti-CMV IgG titer was associated with higher risks for developing CMV disease, undergoing allograft rejection, and eGFR decline.
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- 2021
31. Matcha-like ascites
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Wan‐Yin Cheng, Chih‐Yu Yang, and Der‐Cherng Tarng
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Nephrology ,Ascites ,Humans ,Hematology - Published
- 2021
32. Trajectory of Estimated Glomerular Filtration Rate and Malnourishment Predict Mortality and Kidney Failure in Older Adults With Chronic Kidney Disease
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Shuo-Chun Weng, Chyong-Mei Chen, Yu-Chi Chen, Ming-Ju Wu, and Der-Cherng Tarng
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Medicine (General) ,medicine.medical_specialty ,business.industry ,Hazard ratio ,Renal function ,General Medicine ,medicine.disease ,Lower risk ,mortality ,Confidence interval ,eGFR trajectory ,kidney failure ,R5-920 ,Internal medicine ,Concomitant ,malnourishment ,medicine ,Medicine ,Decompensation ,business ,Body mass index ,older adults ,Kidney disease ,Original Research - Abstract
Objective: The trajectory patterns of estimated glomerular filtration rates (eGFR) in chronic kidney disease (CKD) older adults with malnourishment and their association with subsequent patient outcomes have not been elucidated. We aimed to assess the eGFR trajectory patterns for predicting patient survival and kidney failure in the elderly without or with malnourishment.Materials and Methods: Based on a prospective longitudinal cohort, CKD patients aged 65 years or older were enrolled from 2001 to 2013. Among the 3,948 patients whose eGFR trajectory patterns were analyzed, 1,872 patients were stratified by the absence or presence of malnourishment, and 765 patients were identified and categorized as having malnourishment. Four eGFR trajectory patterns [gradual decline (T0), early non-decline and then persistent decline (T1), persistent increase (T2), and low baseline and then progressive increase (T3)] were classified by utilizing a linear mixed-effect model with a quadratic term in time. The malnourishment was defined as body mass index < 22 kg/m2, serum albumin < 3.0 mg/dL, or Geriatric Nutritional Risk Index (GNRI) < 98. This study assessed the effectiveness of eGFR trajectory patterns in a median follow-up of 2.27 years for predicting all-cause mortality and kidney failure.Results: The mean age was 76.9 ± 6.7 years, and a total of 82 (10.7%) patients with malnourishment and 57 (5.1%) patients without malnourishment died at the end of the study. Compared with the reference trajectory T0, the overall mortality of T1 was markedly reduced [adjusted hazard ratio (aHR) = 0.52, 95% confidence interval (CI) 0.32–0.83]. In patients with trajectory, T3 was associated with a high risk for kidney failure (aHR = 5.68, 95% CI 3.12–10.4) compared with the reference, especially higher risk in the presence of malnourishment. Patients with high GNRI values were significantly associated with a lower risk of death and kidney failure, but patients with malnourishment and concomitant alcohol consumption had a higher risk of kidney failure.Conclusions: Low baseline eGFR and progressively increasing eGFR trajectory were high risks for kidney failure in CKD patients. These findings may be attributed to multimorbidity, malnourishment, and decompensation of renal function.
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- 2021
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33. Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney Biopsy
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Shuo-Ming Ou, Ming-Tsun Tsai, Huan-Yuan Chen, Fu-An Li, Wei-Cheng Tseng, Kuo-Hua Lee, Fu-Pang Chang, Yao-Ping Lin, Ruey-Bing Yang, and Der-Cherng Tarng
- Subjects
Medicine (General) ,Pathology ,medicine.medical_specialty ,kidney biopsy ,Renal function ,RNA-sequencing analysis ,R5-920 ,galectin-3 ,Biopsy ,medicine ,Renal fibrosis ,Original Research ,Kidney ,Proteinuria ,Predictive marker ,medicine.diagnostic_test ,business.industry ,General Medicine ,interstitial fibrosis ,medicine.disease ,medicine.anatomical_structure ,Galectin-3 ,Medicine ,tubular atrophy ,medicine.symptom ,business ,chronic kidney disease ,Kidney disease - Abstract
Background: Galectin-3 (Gal-3) is a multifunctional glycan-binding protein shown to be linked to chronic inflammation and fibrogenesis. Plasma Gal-3 is associated with proteinuria and renal dysfunction, but its role has never been confirmed with kidney biopsy results. In our study, we aimed to explore the expression of Gal-3 in biopsy-proven patients, and we tested the hypothesis that chronic kidney disease (CKD) leads to upregulation of plasma Gal-3 expression in corresponding biopsy findings and RNA sequencing analysis.Method: In 249 patients (male/female: 155/94, age: 57.2 ± 16.3 years) who underwent kidney biopsy, plasma levels of Gal-3 were measured to estimate the association of renal fibrosis. Relationships between plasma Gal-3 levels, estimated glomerular filtration rate (eGFR) and renal histology findings were also assessed. We further examined the gene expression of Gal-3 in RNA-sequencing analysis in biopsy-proven patients.Results: Compared to patients without CKD, CKD patients had higher levels of plasma Gal-3 (1,016.3 ± 628.1 pg/mL vs. 811.6 ± 369.6 pg/ml; P = 0.010). Plasma Gal-3 was inversely correlated with eGFR (P = 0.005) but not with proteinuria. Higher Gal-3 levels were associated with interstitial fibrosis, tubular atrophy and vascular intimal fibrosis. RNA-sequencing analysis showed the upregulation of Gal-3 in fibrotic kidney biopsy samples, and the differentially expressed genes were mainly enhanced in immune cell activation and the regulation of cell-cell adhesion.Conclusions: Plasma Gal-3 levels are inverse correlated with eGFR but positively correlated with renal fibrosis, which may be involved in the immune response and associated pathways. These findings support the role of Gal-3 as a predictive marker of renal fibrosis.
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- 2021
34. Mechanical and chemical cues synergistically promote human venous smooth muscle cell osteogenesis through integrin β1‐ERK1/2 signaling: A cell model of hemodialysis fistula calcification
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Chih Yu Yang, Pu-Yuan Chang, Oscar K. Lee, Bo-Sheng Wu, and Der-Cherng Tarng
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Fistula ,Myocytes, Smooth Muscle ,Cell ,Integrin ,Biochemistry ,Phosphates ,Pathogenesis ,Osteogenesis ,Renal Dialysis ,Genetics ,medicine ,Humans ,Vein ,Molecular Biology ,Mitogen-Activated Protein Kinase 1 ,Mitogen-Activated Protein Kinase 3 ,biology ,business.industry ,Integrin beta1 ,Calcinosis ,medicine.disease ,Cell biology ,RUNX2 ,medicine.anatomical_structure ,Mitochondrial biogenesis ,biology.protein ,Stress, Mechanical ,Cues ,Signal transduction ,Shear Strength ,business ,Signal Transduction ,Biotechnology ,Calcification - Abstract
Arteriovenous fistula (AVF) is the vascular access of choice for renal replacement therapy. However, AVF is susceptible to calcification with a high prevalence of 40%-65% in chronic hemodialysis patients. Repeated needle puncture for hemodialysis cannulation results in intimal denudation of AVF. We hypothesized that exposure to blood shear stress in the medial layer promotes venous smooth muscle cell (SMC) osteogenesis. While previous studies of shear stress focused on arterial-type SMCs, SMCs isolated from the vein had not been investigated. This study established a venous cell model of AVF using the fluid shear device, combined with a high phosphate medium to mimic the uremic milieu. Osteogenic gene expression of venous SMCs upon mechanical and chemical cues was analyzed in addition to the activated cell signaling pathways. Our findings indicated that upon shear stress and high phosphate environment, mechanical stimulation (shear stress) had an additive effect in up-regulation of an early osteogenic marker, Runx2. We further identified that the integrin β1-ERK1/2 signaling pathway was responsible for the molecular basis of venous SMC osteogenesis upon shear stress exposure. Mitochondrial biogenesis also took part in the early stage of this venopathy pathogenesis, evident by the up-regulated mitochondrial transcription factor A and mitochondrial DNA polymerase γ in venous SMCs. In conclusion, synergistic effects of fluid shear stress and high phosphate induce venous SMC osteogenesis via the ERK1/2 pathway through activating the mechanosensing integrin β1 signaling. The present study identified a promising druggable target for reducing AVF calcification, which deserves further in vivo investigations.
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- 2021
35. Sepsis and the Risks of Long-Term Renal Adverse Outcomes in Patients With Chronic Kidney Disease
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Shuo-Ming Ou, Kuo-Hua Lee, Ming-Tsun Tsai, Wei-Cheng Tseng, Yuan-Chia Chu, and Der-Cherng Tarng
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General Medicine - Abstract
BackgroundSepsis is known to cause renal function fluctuations during hospitalization, but whether these patients discharged from sepsis were still at greater risks of long-term renal adverse outcomes remains unknown.MethodsFrom 2011 to 2018, we included 1,12,628 patients with chronic kidney disease (CKD) aged ≥ 20 years. The patients with CKD were further divided into 11,661 sepsis group and 1,00,967 non-sepsis group. The following outcome of interest was included: all-cause mortality, readmission for acute kidney injury, estimated glomerular filtration rate decline ≥50% or doubling of serum creatinine, and end-stage renal disease.ResultsAfter propensity score matching, the sepsis group was at higher risks of all-cause mortality [hazard ratio (HR) 1.39, 95% CI, 1.31–1.47], readmission for acute kidney injury (HR 1.67, 95% CI 1.58–1.76), eGFR decline ≥ 50% or doubling of serum creatinine (HR 3.34, 95% CI 2.78–4.01), and end-stage renal disease (HR 1.43, 95% CI 1.34–1.53) than non-sepsis group.ConclusionsOur study found that patients with CKD discharged from hospitalization for sepsis have higher risks of subsequent renal adverse events.
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- 2021
36. AN69 Filter Membranes with High Ultrafiltration Rates during Continuous Venovenous Hemofiltration Reduce Mortality in Patients with Sepsis-Induced Multiorgan Dysfunction Syndrome
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Shuo-Ming Ou, Wei-Cheng Tseng, Ming Tsun Tsai, Kuo-Hua Lee, Der-Cherng Tarng, Chih Yu Yang, and Yao-Ping Lin
- Subjects
medicine.medical_specialty ,multiple organ failure ,medicine.medical_treatment ,Ultrafiltration ,Urology ,Renal function ,Filtration and Separation ,TP1-1185 ,intensive care unit ,Article ,law.invention ,Sepsis ,Chemical engineering ,law ,Hemofiltration ,medicine ,Chemical Engineering (miscellaneous) ,business.industry ,Chemical technology ,Process Chemistry and Technology ,Multiorgan dysfunction ,blood purification ,medicine.disease ,Intensive care unit ,Membrane ,Continuous venovenous hemofiltration ,critical medicine ,TP155-156 ,business - Abstract
Polyacrylonitrile (AN69) filter membranes adsorb cytokines during continuous venovenous hemofiltration (CVVH). Although high-volume hemofiltration has shown limited benefits, the dose-effect relationship in CVVH with AN69 membranes on severe sepsis remains undetermined. This multi-centered study enrolled 266 patients with sepsis-induced multiorgan dysfunction syndrome (MODS) who underwent CVVH with AN69 membranes between 2014 and 2015. We investigated the effects of ultrafiltration rates (UFR) on mortality. We categorized patients that were treated with UFR of 20–25 mL/kg/h as the standard UFR group (n = 124) and those that were treated with a UFR >, 25 mL/kg/h as the high UFR group (n = 142). Among the patient characteristics, the baseline estimated glomerular filtration rates (eGFR) <, 60 mL/min/1.73 m2, hemoglobin levels <, 10 g/dL, and a sequential organ failure assessment (SOFA) score ≥15 at CVVH initiation were independently associated with in-hospital mortality. In the subgroup analysis, for patients with SOFA scores that were ≥15, the 90-day survival rate was higher in the high UFR group than in the standard UFR group (HR 0.54, CI: 0.36–0.79, p = 0.005). We concluded that in patients with sepsis-induced MODS, SOFA scores ≥15 predicted a poor rate of survival. High UFR setting >, 25 mL/kg/h in CVVH with AN69 membranes may reduce the mortality risk in these high-risk patients.
- Published
- 2021
37. Early elimination of uremic toxin ameliorates AKI-to-CKD transition
- Author
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Chia-Ter Chao, Shing-Hwa Liu, Chih-Kang Chiang, Der-Cherng Tarng, Jenq-Wen Huang, Kuan-Yu Hung, and Jia Huang Chen
- Subjects
medicine.medical_specialty ,Organic anion transporter 1 ,medicine.medical_treatment ,Drug Evaluation, Preclinical ,urologic and male genital diseases ,Butylamines ,Pathogenesis ,Fibrosis ,Internal medicine ,medicine ,Renal fibrosis ,Animals ,Renal Insufficiency, Chronic ,Kidney ,Nephrosclerosis ,biology ,business.industry ,Acute kidney injury ,Oxides ,General Medicine ,Acute Kidney Injury ,medicine.disease ,female genital diseases and pregnancy complications ,Nephrectomy ,Carbon ,Mice, Inbred C57BL ,Endocrinology ,medicine.anatomical_structure ,Reperfusion Injury ,biology.protein ,Unfolded Protein Response ,Senescence-Associated Secretory Phenotype ,business ,Indican ,Kidney disease - Abstract
Acute kidney injury (AKI)-related fibrosis is emerging as a major driver of chronic kidney disease (CKD) development. Aberrant kidney recovery after AKI is multifactorial and still poorly understood. The accumulation of indoxyl sulfate (IS), a protein-bound uremic toxin, has been identified as a detrimental factor of renal fibrosis. However, the mechanisms underlying IS-related aberrant kidney recovery after AKI is still unknown. The present study aims to elucidate the effects of IS on tubular damage and its involvement in the pathogenesis of AKI-to-CKD transition. Our results showed that serum IS started to accumulate associated with the downregulation of tubular organic anion transporter but not observed in the small-molecule uremic toxins of the unilateral ischemia–reperfusion injury (UIRI) without a contralateral nephrectomy model. Serum IS is positively correlated with renal fibrosis and binding immunoglobulin protein (BiP) and CAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) expression induction in the UIRI with a contralateral nephrectomy model (UIRI+Nx). To evaluate the effects of IS in the AKI-to-CKD transition, we administered indole, a precursor of IS, at the early stage of UIRI. Our results demonstrated IS potentiates renal fibrosis, senescence-associated secretory phenotype (SASP), and activation of endoplasmic reticulum (ER) stress, which is attenuated by synergistic AST-120 administration. Furthermore, we clearly demonstrated that IS exposure potentiated hypoxia–reperfusion (H/R) induced G2/M cell cycle arrest, epithelial–mesenchymal transition (EMT) and aggravated ER stress induction in vitro. Finally, the ER chemical chaperon, 4-phenylbutyric acid (4-PBA), successfully reversed the above-mentioned AKI-to-CKD transition. Taken together, early IS elimination in the early stage of AKI is likely to be a useful strategy in the prevention and/or treatment of the AKI-to-CKD transition.
- Published
- 2021
38. An eighth note
- Author
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Meng Rong Tsai, Chiu Yang Lee, Chih Yu Yang, and Der-Cherng Tarng
- Subjects
Advanced and Specialized Nursing ,medicine.medical_specialty ,Eighth note ,Percutaneous ,Arteriovenous Anastomosis ,business.industry ,medicine.medical_treatment ,Arteriovenous fistula ,General Medicine ,medicine.disease ,Collateral circulation ,Stenosis ,Internal medicine ,medicine ,Cardiology ,Vascular Patency ,Radiology, Nuclear Medicine and imaging ,cardiovascular diseases ,Hemodialysis ,Cardiology and Cardiovascular Medicine ,business ,Safety Research - Abstract
Venous stenosis is the most common cause of arteriovenous fistula (AVF) failure in hemodialysis patients. For patients with AVF stenosis, the pressure over the antecedent part of the AVF stenotic lesion will increase if arterial inflow is sufficient. We report a chronic hemodialysis patient who received an angiographic examination for the juxta-anastomosis stenosis of his AVF. A unique feature of a collateral venous branch antecedent to the stenotic lesion was noted, resembling a musical sign as the “eighth note.” After percutaneous transluminal angioplasty, the eighth note attenuated markedly at once. Of note, the eighth note sign is not seen frequently, and thus we postulate that the formation of an eighth note sign on the radiocephalic fistula should fulfill the following requirements, including a sufficient arterial inflow, an adjacent collateral branch close enough to the arteriovenous anastomosis, a severe juxta-anastomotic stenotic lesion, and an intact ulnar venous drainage system.
- Published
- 2021
39. Antithrombotic Therapy for Chronic Kidney Disease Patients With Concomitant Atrial Fibrillation and Coronary Artery Disease
- Author
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Kuo-Hua Lee, Shuo-Ming Ou, Yuan-Chia Chu, Yao-Ping Lin, Ming-Tsun Tsai, and Der-Cherng Tarng
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,acute myocardial infarction ,Cardiovascular Medicine ,Coronary artery disease ,Internal medicine ,Antithrombotic ,medicine ,Diseases of the circulatory (Cardiovascular) system ,atrial fibrillation ,Myocardial infarction ,cardiovascular diseases ,anticoagulation ,Stroke ,Original Research ,business.industry ,Warfarin ,Percutaneous coronary intervention ,Atrial fibrillation ,thromboembolism ,medicine.disease ,stroke ,RC666-701 ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Kidney disease ,medicine.drug - Abstract
Background: Oral anticoagulants (OAC) plus antiplatelets is recommended for patients with atrial fibrillation (AF) and coronary artery disease (CAD) to reduce thromboembolism. However, there is limited evidence regarding antithrombotic therapy for patients with concomitant chronic kidney disease (CKD), AF, and CAD, especially those not undergoing percutaneous coronary intervention. We aimed to use real-world data assessing the efficacy and safety of antithrombotic regimens in this population.Methods: We used a single-center database of 142,624 CKD patients to identify those receiving antithrombotic therapy for AF and CAD between 2010 and 2018. Patients taking warfarin or direct OAC (DOAC) alone were grouped in the OAC monotherapy (n = 537), whereas those taking OAC plus antiplatelets were grouped in the combination therapy (n = 2,391). We conducted propensity score matching to balance baseline covariates. The endpoints were all-cause mortality, major adverse cardiovascular events, and major bleedings.Results: After 1:4 matching, the number of patients in OAC monotherapy and combination therapy were 413 and 1,652, respectively. Between the two groups, combination therapy was associated with higher risks for ischemic stroke (HR 2.37, CI 1.72–3.27), acute myocardial infarction (HR 6.14, CI 2.51–15.0), and hemorrhagic stroke (HR 3.57, CI 1.35–9.81). The results were consistent across CKD stages. In monotherapy, DOAC users were associated with lower risks for all-cause mortality, AMI, and gastrointestinal bleeding than warfarin, but the stroke risk was similar between the two subgroups.Conclusions: For patients with concomitant CKD, AF and CAD not undergoing PCI, OAC monotherapy may reduce stroke and AMI risks. DOAC showed more favorable outcomes than warfarin.
- Published
- 2021
40. Bilirubin Links HO-1 and UGT1A1*28 Gene Polymorphisms to Predict Cardiovascular Outcome in Patients Receiving Maintenance Hemodialysis
- Author
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Tung Po Huang, Ying-Hwa Chen, Der-Cherng Tarng, Tzen-Wen Chen, and Yang Ho
- Subjects
medicine.medical_specialty ,Physiology ,Bilirubin ,medicine.medical_treatment ,Clinical Biochemistry ,Disease ,RM1-950 ,Biochemistry ,Gastroenterology ,digestive system ,heme oxygenase-1 ,UGT1A1 ,chemistry.chemical_compound ,cardiovascular events ,Internal medicine ,Genotype ,Medicine ,In patient ,Molecular Biology ,Gene ,hemodialysis ,business.industry ,Hazard ratio ,Retrospective cohort study ,Cell Biology ,mortality ,chemistry ,Hemodialysis ,Therapeutics. Pharmacology ,business - Abstract
Serum bilirubin levels, which are determined by a complex interplay of various enzymes, including heme oxygenase-1 (HO-1) and uridine diphosphate–glucuronosyl transferase (UGT1A1), may be protective against progression of cardiovascular disease (CVD) in hemodialysis patients. However, the combined effect of HO-1 and UGT1A1*28 gene polymorphisms on CVD outcomes among hemodialysis patients is still unknown. This retrospective study enrolled 1080 prevalent hemodialysis patients and the combined genetic polymorphisms of HO-1 and UGT1A1 on serum bilirubin were analyzed. Endpoints were CVD events and all-cause mortality. Mean serum bilirubin was highest in patients with S/S+S/L of the HO-1 promoter and UGT1A1 7/7 genotypes (Group 1), intermediate in those with S/S+S/L of the HO-1 promoter and UGT1A1 7/6+6/6 genotypes (Group 2), and lowest in the carriers with the L/L HO-1 promoter and UGT1A1 7/6+6/6 genotypes (Group 3) (P <, 0.001). During a median follow-up of 50 months, 433 patients developed CVD. Compared with patients in Group 3, individuals among Groups 1 and 2 had significantly lower risks for CVD events (adjusted hazard ratios (aHRs) of 0.35 for Group 1 and 0.63 for Group 2), respectively. Compared with the lower bilirubin tertile, the aHRs were 0.72 for the middle tertile and 0.40 for the upper tertile for CVD events. We summarized that serum bilirubin as well as HO-1 and UGT1A1 gene polymorphisms were associated with CVD among patients receiving chronic hemodialysis.
- Published
- 2021
41. Relationship between Circulating Galectin-3, Systemic Inflammation, and Protein-Energy Wasting in Chronic Hemodialysis Patients
- Author
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Der-Cherng Tarng, Huan Yuan Chen, Chih Yu Yang, Shuo Ming Ou, Kuo Hua Lee, Ming Tsun Tsai, Ruey Bing Yang, and Wei Cheng Tseng
- Subjects
Male ,Mean arterial pressure ,medicine.medical_specialty ,medicine.medical_treatment ,Galectins ,Systemic inflammation ,Gastroenterology ,Protein-Energy Malnutrition ,Article ,Insulin resistance ,Renal Dialysis ,Internal medicine ,galectin-3 ,medicine ,otorhinolaryngologic diseases ,Humans ,TX341-641 ,Wasting ,Aged ,Inflammation ,systemic inflammation ,Nutrition and Dietetics ,hemodialysis ,business.industry ,Nutrition. Foods and food supply ,Confounding ,Blood Proteins ,Middle Aged ,medicine.disease ,Malnutrition ,Cross-Sectional Studies ,lean tissue mass ,Biomarker (medicine) ,Kidney Failure, Chronic ,protein-energy wasting ,Female ,Hemodialysis ,medicine.symptom ,business ,Food Science - Abstract
Galectin-3 reportedly participates in the inflammatory process that causes insulin resistance in the target tissues. However, the role of high plasma galectin-3 levels as an indicator of protein-energy wasting (PEW) in patients undergoing maintenance hemodialysis remains unclear. This study included 240 hemodialysis patients (64.5 [55.3−74.0] years, 35.8% women) from a tertiary medical center. A baseline assessment of demographic and clinical data, biochemical parameters, and body composition was conducted. Plasma galectin-3 and other biomarkers were measured using a multiplex bead-based immunoassay. Participants were then divided into two subgroups depending on the median value of plasma galectin-3. Malnutrition was identified using the geriatric nutritional risk index (GNRI) and the criteria of the International Society of Renal Nutrition and Metabolism. Independent risk factors for elevated plasma galectin-3 and malnutrition were identified by multivariate logistic regression. The high galectin-3 group was more likely to be older, have lower lean tissue mass and GNRI scores, be diagnosed with PEW, dialyze through a tunneled catheter, and have higher circulating IL-6, TNF-α, and MCP-1 concentrations than the low galectin-3 group. After multivariate adjustment, only low mean arterial pressure, dialyzing with tunneled cuffed catheters, and elevated systemic inflammatory markers correlated with high galectin-3 levels. Plasma galectin-3 concentrations also increased significantly in hemodialysis patients with PEW. However, compared with other commonly used nutritional indicators, galectin-3 did not show superiority in predicting PEW. Although the plasma galectin-3 levels correlated with PEW severity, this correlation disappeared after adjustment for potential confounding variables (OR, 1.000, 95% CI, 0.999–1.001). In conclusion, plasma galectin-3 is a valuable biomarker for systemic inflammation but is less prominent for PEW in patients with maintenance hemodialysis. Further identification of novel biomarkers is required to detect patients at risk for malnutrition and implement appropriate interventions.
- Published
- 2021
42. Bilirubin Links
- Author
-
Yang, Ho, Tzen-Wen, Chen, Tung-Po, Huang, Ying-Hwa, Chen, and Der-Cherng, Tarng
- Subjects
cardiovascular events ,hemodialysis ,heme oxygenase-1 ,UGT1A1 ,digestive system ,mortality ,Article - Abstract
Serum bilirubin levels, which are determined by a complex interplay of various enzymes, including heme oxygenase-1 (HO-1) and uridine diphosphate–glucuronosyl transferase (UGT1A1), may be protective against progression of cardiovascular disease (CVD) in hemodialysis patients. However, the combined effect of HO-1 and UGT1A1*28 gene polymorphisms on CVD outcomes among hemodialysis patients is still unknown. This retrospective study enrolled 1080 prevalent hemodialysis patients and the combined genetic polymorphisms of HO-1 and UGT1A1 on serum bilirubin were analyzed. Endpoints were CVD events and all-cause mortality. Mean serum bilirubin was highest in patients with S/S + S/L of the HO-1 promoter and UGT1A1 7/7 genotypes (Group 1), intermediate in those with S/S + S/L of the HO-1 promoter and UGT1A1 7/6 + 6/6 genotypes (Group 2), and lowest in the carriers with the L/L HO-1 promoter and UGT1A1 7/6 + 6/6 genotypes (Group 3) (p < 0.001). During a median follow-up of 50 months, 433 patients developed CVD. Compared with patients in Group 3, individuals among Groups 1 and 2 had significantly lower risks for CVD events (adjusted hazard ratios (aHRs) of 0.35 for Group 1 and 0.63 for Group 2), respectively. Compared with the lower bilirubin tertile, the aHRs were 0.72 for the middle tertile and 0.40 for the upper tertile for CVD events. We summarized that serum bilirubin as well as HO-1 and UGT1A1 gene polymorphisms were associated with CVD among patients receiving chronic hemodialysis.
- Published
- 2021
43. Impacts of Heart Failure and Physical Performance on Long-Term Mortality in Old Patients With Chronic Kidney Disease
- Author
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Shuo-Chun Weng, Yu-Chi Chen, Chiann-Yi Hsu, Chu-Sheng Lin, Der-Cherng Tarng, and Shih-Yi Lin
- Subjects
medicine.medical_specialty ,Timed Up and Go test ,Cardiovascular Medicine ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,physical functionality ,Internal medicine ,Medicine ,Diseases of the circulatory (Cardiovascular) system ,030212 general & internal medicine ,Stage (cooking) ,ejection fraction ,Survival analysis ,Original Research ,handgrip strength ,Ejection fraction ,business.industry ,Hazard ratio ,timed up-and-go test ,comprehensive geriatric assessment ,medicine.disease ,mortality ,Confidence interval ,Heart failure ,RC666-701 ,Cardiology and Cardiovascular Medicine ,business ,Kidney disease - Abstract
Background: In patients with chronic kidney disease (CKD), physical functional limitations and heart failure (HF) are common, and each is associated with adverse outcomes. However, their joint effects on mortality are not clear.Design and Methods: Using administration data from the geriatric department in a tertiary hospital, retrospective longitudinal analyses of patients aged ≥65 years with CKD were consecutively enrolled from February 2010 to November 2015. Baseline CKD stages, HF with reduced and preserved ejection fraction (HFrEF and HFpEF), Rockwood frailty index, handgrip strength (HGS), 6-m walking speed, and timed up-and-go test were used to predict the prevalence of frailty, physical disability, and all-cause mortality.Results: Among 331 old patients with CKD, their mean age was 81.3 ± 6.6 years. CKD stages showed the following distributions: stage 3, 74.9%; stage 4, 15.7%; stage 5, 9.4%. The prevalence of HF was 23.3%, and Rockwood frailty was 74.3%. Rockwood frailty and HF were both significantly associated with CKD stages. After a mean follow-up period of 3.1 ± 2.1 years, 44 patients died, and a crude analysis showed that stage 4, stage 5 CKD, low HGS, and Rockwood frailty index were associated with mortality. Regarding the survival of these patients, the adjusted mortality hazard ratio for CKD stage 5 was 3.84 against stage 3A [95% confidence interval (CI) 1.51–9.75], 1.04 (95% CI 1.01–1.07) for higher Rockwood frailty score, 4.78 (95% CI 1.26–18.11) for HFrEF, and 3.47 (95% CI 1.15–10.42) for low HGS. Survival analysis using Kaplan–Meier survival plots showed that patients with both HF and poor HGS had the poorest survival.Conclusions: Our study shows that both low physical performance and HF were common in old CKD patients and were associated with CKD stages. HF, frailty, and HGS all independently predicted the mortality of these CKD patients. The mortality is especially high amongst individuals with both HF and decreased HGS.
- Published
- 2021
44. Comparison of Simplified Creatinine Index and Systemic Inflammatory Markers for Nutritional Evaluation of Hemodialysis Patients
- Author
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Der Cherng Tarng, Chih Yu Yang, Ming Tsun Tsai, Shuo Ming Ou, Wei Cheng Tseng, and Kuo Hua Lee
- Subjects
Male ,medicine.medical_specialty ,Multivariate analysis ,medicine.medical_treatment ,030232 urology & nephrology ,Taiwan ,Clinical nutrition ,030204 cardiovascular system & hematology ,Protein-Energy Malnutrition ,Risk Assessment ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Renal Dialysis ,Risk Factors ,Internal medicine ,medicine ,simplified creatinine index ,Humans ,Mass index ,nutritional screening ,TX341-641 ,Wasting ,Inflammation ,systemic inflammation ,Creatinine ,Nutrition and Dietetics ,hemodialysis ,business.industry ,Nutrition. Foods and food supply ,Confounding ,Middle Aged ,Cross-Sectional Studies ,chemistry ,Lean body mass ,protein-energy wasting ,Female ,Hemodialysis ,medicine.symptom ,business ,Biomarkers ,Food Science - Abstract
Protein-energy wasting (PEW) is associated with adverse outcomes in hemodialysis patients. This study compares the simplified creatinine index (SCI) and circulating inflammatory markers as nutritional screening tools for hemodialysis patients. Maintenance hemodialysis patients (230 total patients, 34.8% women, 64.0 ± 14.3 years old) from a tertiary medical center were assessed for demographic data, body composition analysis, biochemistry tests, and circulating inflammatory biomarkers. The SCI was calculated using Canaud’s formula. Reduced fat-free mass index (FFMI), a surrogate of lean body mass, was identified according to the European Society for Clinical Nutrition and Metabolism guidelines. Nutritional status was assessed by the geriatric nutritional risk index (GNRI) and International Society of Renal Nutrition and Metabolism (ISRNM) criteria. Multivariate logistic regression revealed independent risk factors for low FFMI and malnutrition. Of the patients, 47.4% had low FFMI. Patients with a reduction in FFMI tended to be older females with lower body mass index, SCI, and GNRI scores but significantly higher levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-8. SCI was found to be an independent predictor for reduced FFMI (OR 0.57, 95% CI 0.40–0.81) and presence of PEW according to ISRNM criteria (OR 0.38, 95% CI 0.21–0.68). Although a positive association between systemic inflammatory markers and low FFMI was observed, this association disappeared in multivariate analysis. Moreover, the inflammatory markers examined in this study were not associated with malnutrition after adjusting for potential confounders. Compared with markers of systemic inflammation, SCI achieved better performance in assessing the nutritional status of hemodialysis patients.
- Published
- 2021
45. MMP-9 Deletion Attenuates Arteriovenous Fistula Neointima through Reduced Perioperative Vascular Inflammation
- Author
-
Yu Chung Shih, Po Hsun Huang, Hsu Ma, Tai Ming Ko, Der Cherng Tarng, and Po Yuan Chen
- Subjects
0301 basic medicine ,Male ,Pathology ,Vascular smooth muscle ,Fistula ,030204 cardiovascular system & hematology ,Muscle, Smooth, Vascular ,Mice ,0302 clinical medicine ,Cell Movement ,vascular inflammation ,Biology (General) ,Spectroscopy ,Mice, Knockout ,Cell migration ,General Medicine ,musculoskeletal system ,Computer Science Applications ,Chemistry ,Matrix Metalloproteinase 9 ,Knockout mouse ,Arteriovenous Fistula ,cardiovascular system ,Neointima ,medicine.medical_specialty ,QH301-705.5 ,Myocytes, Smooth Muscle ,Arteriovenous fistula ,Vascular Remodeling ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,medicine ,Animals ,cardiovascular diseases ,Physical and Theoretical Chemistry ,Perioperative Period ,Molecular Biology ,QD1-999 ,Inflammation ,business.industry ,Organic Chemistry ,neointima ,medicine.disease ,Mice, Inbred C57BL ,030104 developmental biology ,MRNA Sequencing ,AV Fistula Stenosis ,business - Abstract
Matrix metalloproteinase 9 (MMP-9) expression is upregulated in vascular inflammation and participates in vascular remodeling, including aneurysm dilatation and arterial neointima development. Neointima at the arteriovenous (AV) fistula anastomosis site primarily causes AV fistula stenosis and failure, however, the effects of MMP-9 on perioperative AV fistula remodeling remain unknown. Therefore, we created AV fistulas (end-to-side anastomosis) in wild-type (WT) and MMP-9 knockout mice with chronic kidney disease to further clarify this. Neointima progressively developed in the AV fistula venous segment of WT mice during the four-week postoperative course, and MMP-9 knockout increased the lumen area and attenuated neointima size by reducing smooth muscle cell and collagen components. Early perioperative AV fistula mRNA sequencing data revealed that inflammation-related gene sets were negatively enriched in AV fistula of MMP-9 knockout mice compared to that in WT mice. qPCR results also showed that inflammatory genes, including tumor necrosis factor-a (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), were downregulated. In addition, Western blot results showed that MMP-9 knockout reduced CD44 and RAC-alpha serine/threonine-protein kinase (Akt) and extracellular signal-regulated kinases (ERK) phosphorylation. In vitro, MMP-9 addition enhanced IL-6 and MCP-1 expression in vascular smooth muscle cells, as well as cell migration, which was reversed by an MMP-9 inhibitor. In conclusion, MMP-9 knockout attenuated AV fistula stenosis by reducing perioperative vascular inflammation.
- Published
- 2021
46. Role of prognostic biomarker decoy receptor 3 and immunomodulation in kidney diseases
- Author
-
Der Cherng Tarng and Shuo Chun Weng
- Subjects
030204 cardiovascular system & hematology ,Nephropathy ,Immunomodulation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,In vivo ,medicine ,Renal fibrosis ,Animals ,Humans ,Creatinine ,Kidney ,business.industry ,Receptors, Tumor Necrosis Factor, Member 6b ,General Medicine ,Prognosis ,medicine.disease ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,Biomarker (medicine) ,Kidney Diseases ,Decoy receptor 3 ,business ,Biomarkers ,Kidney disease - Abstract
Decoy receptor 3 (DcR3), also known as tumor necrosis factor receptor superfamily member 6b (TNFRSF6B), was recently identified as a novel biomarker for predicting progression of kidney diseases with potential immune modulation. The purpose of this review is to discuss the current evidence related to DcR3 in kidney diseases and to compare the differences between human and animal studies both in vivo and in vitro. High serum DcR3 predicts the occurrence of peritonitis in patients receiving chronic peritoneal dialysis and is positively correlated with inflammatory markers such as interleukin-6, high-sensitivity C-reactive protein, and adhesion molecules in patients on maintenance hemodialysis (HD). Higher serum DcR3 levels not only independently predict cardiovascular and all-cause mortality in HD patients but also identify older adults on HD at risk of protein-energy wasting in combination with a low geriatric nutritional risk index. Recently, renal tubular epithelial cells (RTECs) expressing DcR3 have also been used to predict progression of chronic kidney disease. Expression of DcR3 was correlated with a 2-fold increase in serum creatinine or failure of kidney allograft. DcR3 could protect renal myofibroblasts against Fas-induced apoptosis and subsequently lead to renal fibrosis. Locally expressed DcR3 in the RTECs may suppress the FasL-Fas-mediated apoptosis of T cells, resulting in an accumulation of allo-reactive T cells. In addition to traditional biological functions, recombinant DcR3.Fc and cytomegalovirus promoter-driven human DcR3 plasmid are able to modulate the activation and differentiation of dendritic cells and macrophages via "non-decoy" action. Both progressive IgA nephropathy and autoimmune crescentic glomerulonephritis in mice can be suppressed after hydrodynamics-based gene delivery of DcR3 plasmid. DcR3-mediated effects in vitro could be surveyed via over-expressing DcR3 or addition of recombinant DcR3.Fc, and CD68-driven DcR3 transgenic mice are suitable for investigating systemic effect in vivo. Inhibition of DcR3 expression in human may be a promising approach for pathomechanism.
- Published
- 2019
47. Functioning tailor-made 3D-printed vascular graft for hemodialysis
- Author
-
Ming-Chia Li, Pu-Yuan Chang, Huai-Rou Luo, Ling-Yuan Chang, Chuan-Yi Lin, Chih-Yu Yang, Oscar Kuang-Sheng Lee, Yan-Hwa Wu Lee, and Der-Cherng Tarng
- Subjects
Nephrology ,Surgery - Abstract
Background: The two ends of arteriovenous graft (AVG) are anastomosed to the upper limb vessels by surgery for hemodialysis therapy. However, the size of upper limb vessels varies to a large extent among different individuals. Methods: According to the shape and size of neck vessels quantified from the preoperative computed tomography angiographic scan, the ethylene-vinyl acetate (EVA)-based AVG was produced in H-shape by the three-dimensional (3D) printer and then sterilized. This study investigated the function of this novel 3D-printed AVG in vitro and in vivo. Results: This 3D-printed AVG can be implanted in the rabbit’s common carotid artery and common jugular vein with ease and functions in vivo. The surgical procedure was quick, and no suture was required. The blood loss was minimal, and no hematoma was noted at least 1 week after the surgery. The blood flow velocity within the implanted AVG was 14.9 ± 3.7 cm/s. Additionally, the in vitro characterization experiments demonstrated that this EVA-based biomaterial is biocompatible and possesses a superior recovery property than ePTFE after hemodialysis needle cannulation. Conclusions: Through the 3D printing technology, the EVA-based AVG can be tailor-made to fit the specific vessel size. This kind of 3D-printed AVG is functioning in vivo, and our results realize personalized vascular implants. Further large-animal studies are warranted to examine the long-term patency.
- Published
- 2022
48. Mo1591: FK506 BINDING PROTEIN 5 DEFICIENCY REGULATES GUT MICROBIOTA AND GUT BARRIER AGAINST LIPOPOLYSACCHARIDE-INDUCED ACUTE KIDNEY INJURY IN MICE
- Author
-
Jia-Rou Hsu, Chia Yen Chen, Shih-Chieh Lai, Yi-Chen Huang, Pin Hao Ko, Yu-Chin Huang, Der-Cherng Tarng, and Li-Ling Wu
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
49. Diet, gut microbiome and indoxyl sulphate in chronic kidney disease patients
- Author
-
Chih Yu Yang and Der Cherng Tarng
- Subjects
education.field_of_study ,business.industry ,Prebiotic ,medicine.medical_treatment ,Population ,030232 urology & nephrology ,Renal function ,Physiology ,Inflammation ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,law.invention ,03 medical and health sciences ,Probiotic ,0302 clinical medicine ,Nephrology ,law ,medicine ,medicine.symptom ,business ,education ,Dysbiosis ,Pathological ,Kidney disease - Abstract
Emerging evidence suggests that intestinal dysbiosis plays an important role in host inflammation locally and systemically. Such pathological condition is even more prevailing in patients with chronic kidney disease (CKD). Of note, indoxyl sulphate (IS), a gut-derived uremic toxin, is notorious for its pro-inflammatory feature in CKD patients. IS accumulates in the body as the urinary excretion of uremic toxins is impaired, and further worsens the kidney function in a vicious cycle to CKD. Dietary restriction in vegetables, fruits and yogurt leads to the predominance of indole-producing intestinal microbial flora and further exaggerates the accumulation of IS in CKD patients. Recently, interventional studies have shown that circulating IS can be reduced by dietary prebiotic and/or probiotic supplements. However, further randomized controlled trials are warranted to examine whether such beneficial effect of dietary prebiotic/probiotic supplements could be extrapolated to better hard outcomes in CKD population. In this review, we would also like to emphasize the importance of achieving sufficient intake of dietary fibre by proper vegetable pre-treatment and accurate fruit selection, instead of directly avoiding these potassium-rich yet fibre-rich and base-producing foods.
- Published
- 2018
50. Hypoxic mesenchymal stem cells ameliorate acute kidney ischemia-reperfusion injury via enhancing renal tubular autophagy
- Author
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Nien Jung Chen, Ming Tsun Tsai, Der Cherng Tarng, Fu Pang Chang, Chiang Ting Chien, Wei Cheng Tseng, Shih-Chieh Hung, and Pei Ying Lee
- Subjects
Male ,Medicine (General) ,ATG5 ,Medicine (miscellaneous) ,Ischemia-reperfusion injury ,Apoptosis ,QD415-436 ,urologic and male genital diseases ,Kidney ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Biochemistry ,Rats, Sprague-Dawley ,R5-920 ,Ischemia ,medicine ,Autophagy ,Animals ,Humans ,Hypoxia ,Tissue homeostasis ,Renal ischemia ,business.industry ,urogenital system ,Research ,Mesenchymal stem cell ,Acute kidney injury ,Mesenchymal Stem Cells ,Hypoxic mesenchymal stem cells ,Cell Biology ,Acute Kidney Injury ,medicine.disease ,equipment and supplies ,Rats ,Reperfusion Injury ,Reperfusion ,Cancer research ,Molecular Medicine ,Stem cell ,business ,Reperfusion injury - Abstract
Background Acute kidney injury (AKI) is an emerging global healthcare issue without effective therapy yet. Autophagy recycles damaged organelles and helps maintain tissue homeostasis in acute renal ischemia-reperfusion (I/R) injury. Hypoxic mesenchymal stem cells (HMSCs) represent an innovative cell-based therapy in AKI. Moreover, the conditioned medium of HMSCs (HMSC-CM) rich in beneficial trophic factors may serve as a cell-free alternative therapy. Nonetheless, whether HMSCs or HMSC-CM mitigate renal I/R injury via modulating tubular autophagy remains unclear. Methods Renal I/R injury was induced by clamping of the left renal artery with right nephrectomy in male Sprague-Dawley rats. The rats were injected with either PBS, HMSCs, or HMSC-CM immediately after the surgery and sacrificed 48 h later. Renal tubular NRK-52E cells subjected to hypoxia-reoxygenation (H/R) injury were co-cultured with HMSCs or treated with HMSC-CM to assess the regulatory effects of HSMCs on tubular autophagy and apoptosis. The association of tubular autophagy gene expression and renal recovery was also investigated in patients with ischemic AKI. Result HMSCs had a superior anti-oxidative effect in I/R-injured rat kidneys as compared to normoxia-cultured mesenchymal stem cells. HMSCs further attenuated renal macrophage infiltration and inflammation, reduced tubular apoptosis, enhanced tubular proliferation, and improved kidney function decline in rats with renal I/R injury. Moreover, HMSCs suppressed superoxide formation, reduced DNA damage and lipid peroxidation, and increased anti-oxidants expression in renal tubular epithelial cells during I/R injury. Co-culture of HMSCs with H/R-injured NRK-52E cells also lessened tubular cell death. Mechanistically, HMSCs downregulated the expression of pro-inflammatory interleukin-1β, proapoptotic Bax, and caspase 3. Notably, HMSCs also upregulated the expression of autophagy-related LC3B, Atg5 and Beclin 1 in renal tubular cells both in vivo and in vitro. Addition of 3-methyladenine suppressed the activity of autophagy and abrogated the renoprotective effects of HMSCs. The renoprotective effect of tubular autophagy was further validated in patients with ischemic AKI. AKI patients with higher renal LC3B expression were associated with better renal recovery. Conclusion The present study describes that the enhancing effect of MSCs, and especially of HMCSs, on tissue autophagy can be applied to suppress renal tubular apoptosis and attenuate renal impairment during renal I/R injury in the rat. Our findings provide further mechanistic support to HMSCs therapy and its investigation in clinical trials of ischemic AKI.
- Published
- 2021
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