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Article: Chronic Kidney Disease-How Does It Go, and What Can We Do and Expect?

Chang, Li-Yun / Chang, Jer-Ming

2023 Volume 11, Issue 3

Abstract: Chronic kidney disease (CKD), as a worldwide threat to public health, is a key determinant of poor health outcomes, but the severity of the problem is probably not fully appreciated [ ... ]. ...

Abstract	Chronic kidney disease (CKD), as a worldwide threat to public health, is a key determinant of poor health outcomes, but the severity of the problem is probably not fully appreciated [...].
Language	English
Publishing date	2023-03-22
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11030977
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Article: Diabetic Kidney Disease in Post-Transplant Diabetes Mellitus: Causes, Treatment and Outcomes.

Lim, Lee-Moay / Chang, Jer-Ming / Kuo, Hung-Tien

Biomedicines

2023 Volume 11, Issue 2

Abstract: Kidney transplant recipients are a unique subgroup of chronic kidney disease patients due to their single functioning kidney, immunosuppressive agent usage, and long-term complications related to transplantation. Post-transplant diabetes mellitus (PTDM) ... ...

Abstract	Kidney transplant recipients are a unique subgroup of chronic kidney disease patients due to their single functioning kidney, immunosuppressive agent usage, and long-term complications related to transplantation. Post-transplant diabetes mellitus (PTDM) has a significant adverse effect on renal outcomes in particular. As transplantations enable people to live longer, cardiovascular morbidity and mortality become more prevalent, and PTDM is a key risk factor for these complications. Although PTDM results from similar risk factors to those of type 2 diabetes, the conditions differ in their pathophysiology and clinical features. Transplantation itself is a risk factor for diabetes due to chronic exposure to immunosuppressive agents. Considering current evidence, this article describes the risk factors, pathogenesis, diagnostic criteria, prevention strategies, and management of PTDM. The therapeutic options are discussed regarding their safety and potential drug-drug interactions with immunosuppressive agents.
Language	English
Publishing date	2023-02-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11020470
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Article ; Online: Generation of endoplasmic reticulum stress-dependent reactive oxygen species mediates TGF-β1-induced podocyte migration.

Chen, Chien-An / Chang, Jer-Ming / Chen, Hung-Chun / Chang, Eddy-Essen

Journal of biochemistry

2022 Volume 171, Issue 3, Page(s) 305–314

Abstract: Podocyte migration results in proteinuria and glomerulonephropathy. Transforming growth factor-β1 (TGF-β1), endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) can mediate podocyte migration; however, the crosstalk between them is unclear. ...

Abstract	Podocyte migration results in proteinuria and glomerulonephropathy. Transforming growth factor-β1 (TGF-β1), endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) can mediate podocyte migration; however, the crosstalk between them is unclear. This study determined the relationships between these factors. ER stress biomarkers (GRP78, p-eIF2α or CHOP), intracellular ROS generation, integrin-β3 and cell adhesion and migration were studied in a treatment of experiment using TGF-β1 with and without the ER stress inhibitors: 4-phenylbutyric acid (4-PBA, a chemical chaperone), salubrinal (an eIF2α dephosphorylation inhibitor) and N-acetylcysteine (NAC, an antioxidant). ER stress biomarkers (p-eIF2α/eIF2α and GRP78), ROS generation and intergrin-β3 expression increased after TGF-β1 treatment. NAC down-regulated the expression of GRP78 after TGF-β1 treatment. 4-PBA attenuated TGF-β1-induced p-eIF2α/eIF2α, CHOP, ROS generation and intergrin-β3 expression. However, salubrinal did not inhibit TGF-β1-induced p-eIF2α/eIF2α, CHOP, ROS generation or integrin-β3 expression. NAC abrogated TGF-β1-induced integrin-β3 expression. At 24 h after treatment with TGF-β1, podocyte adhesion and migration increased. Furthermore, NAC, 4-PBA and an anti-interin-β3 antibody attenuated TGF-β1-induced podocyte adhesion and migration. This study demonstrated that TGF-β1-induced ER stress potentiates the generation of intracellular ROS to a high degree through the PERK/eIF2α/CHOP pathway. This intracellular ROS then mediates integrin-β3 expression, which regulates podocyte migration.
MeSH term(s)	Apoptosis ; Cell Movement ; Endoplasmic Reticulum Stress ; Podocytes/metabolism ; Reactive Oxygen Species/metabolism ; Transforming Growth Factor beta1/metabolism ; Transforming Growth Factor beta1/pharmacology
Chemical Substances	Reactive Oxygen Species ; Transforming Growth Factor beta1
Language	English
Publishing date	2022-01-06
Publishing country	England
Document type	Journal Article
ZDB-ID	218073-x
ISSN	1756-2651 ; 0021-924X
ISSN (online)	1756-2651
ISSN	0021-924X
DOI	10.1093/jb/mvab128
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Article ; Online: Podocentric view of glomerular proteinuria: Focused on cytoskeletal changes and toward promising targeted therapies and challenges.

Kuo, Mei-Chuan / Liang, Peir-In / Chang, Jer-Ming

The Kaohsiung journal of medical sciences

2021 Volume 37, Issue 7, Page(s) 539–546

Abstract: Among renal cells, podocytes (glomerular epithelial cells) are the most critical to prevent plasma proteins from excessive loss by forming their sophisticated foot processes (FP) and slit diaphragms (SD). A general finding in the glomeruli of patients ... ...

Abstract	Among renal cells, podocytes (glomerular epithelial cells) are the most critical to prevent plasma proteins from excessive loss by forming their sophisticated foot processes (FP) and slit diaphragms (SD). A general finding in the glomeruli of patients with nephrotic syndrome is the foot processes "effacement" resulted from dysregulated actin cytoskeleton reorganization. Ultrastructural analysis in patients with nephrotic syndrome has demonstrated that such changes tend to be dynamic and can sometimes be reversible. In a more molecular sense, injured podocytes can no longer maintain their tight regulation and "retract" their FP, but not "efface" them. Past studies have revealed multiple exquisite mechanisms and arrays of proteins participating in the regulation of cytoskeletal rearrangement, and these mechanisms serve as potential targets to treat. A major challenge to develop specific therapies is the targeted mechanism has to be crucial and specific enough for podocyte-oriented kidney diseases, and it would be even better to manifest in most of the glomerulonephritis. Studies have shown many approaches targeting different mechanisms, but none of them has been proved to be effective in clinical medicine. Up to the present, Abatacept (Orencia) is the first (and the only) clinical targeted therapy demonstrating limited success. It inhibits the co-stimulatory response of B7-1 (CD80) induced in various types of glomerulonephritis. Future clinical studies have to be expanded to substantiate this highly specific targeted therapy because the Abatacept effect is not generally accepted even within the nephrology community. Nevertheless, there are ongoing searches for specific treatment targeting podocytes through various approaches.
MeSH term(s)	Abatacept/pharmacology ; Animals ; B7-1 Antigen/metabolism ; Basement Membrane/metabolism ; Cytoskeleton/metabolism ; Epithelial Cells ; Glomerulonephritis/metabolism ; Glomerulonephritis/therapy ; Humans ; Kidney/metabolism ; Kidney Glomerulus/metabolism ; Mice ; Nephrology/methods ; Nephrotic Syndrome/metabolism ; Nephrotic Syndrome/therapy ; Podocytes/metabolism ; Proteinuria ; Rats ; Signal Transduction
Chemical Substances	B7-1 Antigen ; CD80 protein, human ; Abatacept (7D0YB67S97)
Language	English
Publishing date	2021-05-04
Publishing country	China (Republic : 1949- )
Document type	Journal Article ; Review
ZDB-ID	639302-0
ISSN	2410-8650 ; 0257-5655
ISSN (online)	2410-8650
ISSN	0257-5655
DOI	10.1002/kjm2.12385
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Article ; Online: Sex difference in the associations among liver function parameters with incident diabetes mellitus in a large Taiwanese population follow-up study.

Chen, Yi-Kong / Wu, Pei-Yu / Huang, Jiun-Chi / Chen, Szu-Chia / Chang, Jer-Ming

Frontiers in public health

2023 Volume 10, Page(s) 1081374

Abstract: Background: The prevalence of diabetes mellitus (DM) in Taiwan between 2017 and 2020 was 11.05%, which is higher than the global prevalence (10.5%). Previous studies have shown that patients with DM have higher liver enzyme levels than those without DM. ...

Abstract	Background: The prevalence of diabetes mellitus (DM) in Taiwan between 2017 and 2020 was 11.05%, which is higher than the global prevalence (10.5%). Previous studies have shown that patients with DM have higher liver enzyme levels than those without DM. However, it is unclear whether there are sex differences in the association between incident DM and liver function. Therefore, the aim of this longitudinal study was to investigate this issue in a large Taiwanese cohort. Methods: We identified 27,026 participants from the Taiwan Biobank, and excluded those with baseline DM ( Results: Of the enrolled participants, 1,109 (4.6%) had incident DM and 23,237 (95.4%) did not. Multivariable analysis showed that high levels of glutamic-oxaloacetic transaminase (AST) ( Conclusion: In conclusion, liver function parameters were significantly associated with incident DM. Further, there were differences in the associations between the male and female participants.
MeSH term(s)	Adult ; Female ; Humans ; Male ; Middle Aged ; Bilirubin/blood ; Diabetes Mellitus/epidemiology ; Follow-Up Studies ; gamma-Glutamyltransferase/blood ; Liver/physiopathology ; Longitudinal Studies ; Sex Factors
Chemical Substances	Bilirubin (RFM9X3LJ49) ; gamma-Glutamyltransferase (EC 2.3.2.2)
Language	English
Publishing date	2023-01-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2022.1081374
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Article: The Association between Iron Deficiency and Renal Outcomes Is Modified by Sex and Anemia in Patients with Chronic Kidney Disease Stage 1-4.

Yu, Pei-Hua / Chao, Yu-Lin / Kuo, I-Ching / Niu, Sheng-Wen / Chiu, Yi-Wen / Chang, Jer-Ming / Hung, Chi-Chih

Journal of personalized medicine

2023 Volume 13, Issue 3

Abstract: Iron deficiency is prevalent in women and patients with chronic kidney disease (CKD). Iron deficiency is not only related to anemia but contributes to adverse consequences for the kidney as well. Whether iron status is associated with renal outcomes ... ...

Abstract	Iron deficiency is prevalent in women and patients with chronic kidney disease (CKD). Iron deficiency is not only related to anemia but contributes to adverse consequences for the kidney as well. Whether iron status is associated with renal outcomes after considering sex and anemia in patients with CKD stage 1-4 is unclear. Thus, we investigated the association of iron or iron saturation with renal outcomes in a CKD cohort. During a follow-up of 8.2 years, 781 (31.2%) patients met the composite renal outcome of renal replacement therapy and a 50% decline in renal function. In linear regression, iron was associated with sex, hemoglobin (Hb), and nutritional markers. In a fully adjusted Cox regression model, the male patients with normal iron had a significantly decreased risk of renal outcomes (hazard ratio (HR) 0.718; 95% confidence interval (CI) 0.579 to 0.889), but the female patients did not exhibit this association. The non-anemic patients (Hb ≥ 11 g/dL) had a decreased risk of renal outcomes (HR 0.715; 95% CI 0.568 to 0.898), but the anemic patients did not. In the sensitivity analysis, transferrin saturation (TSAT) showed similar results. When comparing iron and TSAT, both indicators showed similar prognostic values. In conclusion, iron deficiency, indicated by either iron or iron saturation, was associated with poor renal outcomes in the male or non-anemic patients with CKD stage 1-4.
Language	English
Publishing date	2023-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm13030521
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Article ; Online: Synergetic Association between Anemia and Hyperuricemia on New-Onset Chronic Kidney Disease in a Large Taiwanese Population Follow-Up Study.

Chen, You-Chi / Liu, Yi-Hsueh / Wu, Pei-Yu / Huang, Jiun-Chi / Su, Ho-Ming / Chen, Szu-Chia / Chang, Jer-Ming

International journal of environmental research and public health

2023 Volume 20, Issue 2

Abstract: The incidence of chronic kidney disease (CKD) is increasing worldwide; however, the association between CKD and anemia and hyperuricemia has yet to be clarified. In addition, whether anemia and hyperuricemia only influence renal damage in combination ... ...

Abstract	The incidence of chronic kidney disease (CKD) is increasing worldwide; however, the association between CKD and anemia and hyperuricemia has yet to be clarified. In addition, whether anemia and hyperuricemia only influence renal damage in combination with other comorbidities or whether they are direct causative factors is also controversial. Therefore, the aim of this longitudinal study was to investigate these issues in a large Taiwanese cohort. We enrolled 26,631 participants from the Taiwan Biobank (TWB) after excluding those with CKD at the baseline, all of whom had follow-up data for a median of 4 years. In this study, CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2, incident new-onset CKD was defined as the development of CKD during follow-up, anemia was defined as a hemoglobin level <13 mg/dL in males and <12 mg/dL in females, and hyperuricemia was defined as a serum uric acid (UA) level >7 mg/dL in males and >6 mg/dL in females. The participants were divided into four groups according to whether or not they had anemia and hyperuricemia. Multivariable analysis showed that low hemoglobin (per 1 g/dL; odds ratio [OR], 0.760; p < 0.001) and high serum UA (per 1 mg/dL; OR, 1.444; p < 0.001) in model 1 and anemia (OR, 2.367; p < 0.001) and hyperuricemia (OR, 2.516; p < 0.001) in model 2 were significantly associated with new-onset CKD. Furthermore, compared to the group without anemia or hyperuricemia, the groups with anemia without hyperuricemia (OR, 2.502; p < 0.001), without anemia with hyperuricemia (OR, 2.559; p < 0.001), and with anemia and hyperuricemia (OR, 5.505; p < 0.001) were significantly associated with new-onset CKD. There was a significant interaction between hemoglobin and serum UA and new-onset CKD (p < 0.001). In conclusion, we found that anemia and hyperuricemia were associated with new-onset CKD, respectively, and also had a synergetic effect on new-onset CKD.
MeSH term(s)	Male ; Female ; Humans ; Follow-Up Studies ; Longitudinal Studies ; Hyperuricemia/complications ; Hyperuricemia/epidemiology ; Uric Acid ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/etiology ; Anemia/etiology ; Anemia/complications ; Glomerular Filtration Rate ; Risk Factors
Chemical Substances	Uric Acid (268B43MJ25)
Language	English
Publishing date	2023-01-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph20021421
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Article: Association and Interaction between Heavy Metals and Hyperuricemia in a Taiwanese Population.

Lu, Lu-Heng / Tsai, Chun-Chi / Lin, Chih-Yi / Wang, Chih-Wen / Wu, Pei-Yu / Huang, Jiun-Chi / Chen, Szu-Chia / Chang, Jer-Ming

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 10

Abstract: The prevalence of hyperuricemia in Taiwan is high, and hyperuricemia has been associated with a risk of developing several diseases. Although the traditional risk factors for hyperuricemia are well known, the relationship between heavy metals and ... ...

Abstract	The prevalence of hyperuricemia in Taiwan is high, and hyperuricemia has been associated with a risk of developing several diseases. Although the traditional risk factors for hyperuricemia are well known, the relationship between heavy metals and hyperuricemia is still undefined. Therefore, the aim of this study was to investigate the relationship between hyperuricemia and heavy metals. A total of 2447 participants (977 males and 1470 females) residing in southern Taiwan were enrolled, and levels of the following heavy metals were measured: lead in blood, and nickel, chromium, manganese, arsenic (As), copper, and cadmium in urine. Hyperuricemia was defined as a serum uric acid level greater than 7.0 mg/dL (416.5 μmol/L) in men and 6.0 mg/dL (357 μmol/L) in women. The participants were divided into two groups: those without hyperuricemia (
Language	English
Publishing date	2023-05-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13101741
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Article ; Online: Cerebral white matter burden is linked to cognitive function in patients undergoing hemodialysis.

Wu, Tsai-Shan / Wu, Ping-Hsun / Lin, Hsiu-Fen / Chen, Wen-Ching / Huang, Teng-Hui / Lin, Ming-Yen / Chuang, Yun-Shiuan / Yang, Fan-Pei Gloria / Chiu, Yi-Wen / Chang, Jer-Ming / Kuo, Mei-Chuan / Lin, Yi-Ting

Annals of medicine

2024 Volume 56, Issue 1, Page(s) 2310142

Abstract: Introduction: Chronic kidney disease is related to neurodegeneration and structural changes in the brain which might lead to cognitive decline. The Fazekas scale used for assessing white matter hyperintensities (WMHs) was associated with poor cognitive ... ...

Abstract	Introduction: Chronic kidney disease is related to neurodegeneration and structural changes in the brain which might lead to cognitive decline. The Fazekas scale used for assessing white matter hyperintensities (WMHs) was associated with poor cognitive performance. Therefore, this study investigated the associations between the mini-mental status examination (MMSE), Montreal cognitive assessment (MoCA), cognitive abilities screening instrument (CASI), and Fazekas scale in patients under hemodialysis (HD). Methods: The periventricular (PV) WMHs and deep WMHs (DWMHs) in brain magnetic resonance images of 59 patients under dialysis were graded using the Fazekas scale. Three cognition function tests were also performed, then multivariable ordinal regression and logistic regression were used to identify the associations between cognitive performance and the Fazekas scale. Results: There were inverse associations between the three cognitive function tests across the Fazekas scale of PVWMHs ( Conclusion: An inverse correlation existed between the Fazekas scale, predominantly in PVWMHs, and cognition in patients undergoing HD. The PVWMHs were associated with cognitive performance assessed by MMSE, MoCA, and CASI, as well as with subdomains of CASI such as memory, language and name fluency in patients undergoing HD.
MeSH term(s)	Humans ; White Matter/diagnostic imaging ; White Matter/pathology ; Cognition ; Brain/diagnostic imaging ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/diagnosis ; Magnetic Resonance Imaging ; Renal Dialysis/adverse effects
Language	English
Publishing date	2024-02-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1004226-x
ISSN	1365-2060 ; 1651-2219 ; 0785-3890 ; 1743-1387
ISSN (online)	1365-2060 ; 1651-2219
ISSN	0785-3890 ; 1743-1387
DOI	10.1080/07853890.2024.2310142
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Article ; Online: Association Between Trimethylamine N-oxide and Adverse Kidney Outcomes and Overall Mortality in Type 2 Diabetes Mellitus.

Yu, Ping-Shaou / Wu, Ping-Hsun / Hung, Wei-Wen / Lin, Ming-Yen / Zhen, Yen-Yi / Hung, Wei-Chun / Chang, Jer-Ming / Tsai, Jong-Rung / Chiu, Yi-Wen / Hwang, Shang-Jyh / Tsai, Yi-Chun

The Journal of clinical endocrinology and metabolism

2024

Abstract: Context: Type 2 diabetes (T2D) is the major contributor to chronic kidney disease and end-stage kidney disease (ESKD). The influence of trimethylamine N-oxide (TMAO) on kidney outcomes in T2D remains unclear.: Objective: To examine the association ... ...

Abstract	Context: Type 2 diabetes (T2D) is the major contributor to chronic kidney disease and end-stage kidney disease (ESKD). The influence of trimethylamine N-oxide (TMAO) on kidney outcomes in T2D remains unclear. Objective: To examine the association between fasting serum TMAO levels and adverse kidney outcomes in patients with T2D. Methods: Between October 2016 and June 2020, patients with T2D were recruited and monitored every 3 months until December 2021. Serum TMAO levels were assessed using liquid chromatography-mass spectrometry. The primary kidney outcomes were doubling of serum creatinine levels or progression to ESKD necessitating dialysis; the secondary kidney outcome was a rapid 30% decline in estimated glomerular filtration rate within 2 years. All-cause mortality was also evaluated. Results: Among the 440 enrolled patients with T2D, those in the highest serum TMAO tertile (≥0.88 μM) were older, had a longer diabetes duration, elevated blood urea nitrogen, and lower estimated glomerular filtration rate. Over a median follow-up period of 4 years, 26 patients (5.9%) had a doubling of serum creatinine level or progression to ESKD. After propensity score weighting, the patients in the highest serum TMAO tertile had a 6.45-fold increase in the risk of doubling of serum creatinine levels or progression to ESKD and 5.86-fold elevated risk of rapid decline in kidney function compared with those in the lowest tertile. Additionally, the stepwise increase in serum TMAO was associated with all-cause mortality. Conclusion: Patients with T2D with elevated circulating TMAO levels are at higher risk of doubling serum creatinine, progressing to ESKD, and mortality. TMAO is a potential biomarker for kidney function progression and mortality in patients with T2D.
Language	English
Publishing date	2024-01-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgae009
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