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Article: Aging and Renal Disease: Old Questions for New Challenges.

Chou, Yu-Hsiang / Chen, Yung-Ming

Aging and disease

2021 Volume 12, Issue 2, Page(s) 515–528

Abstract: Chronic kidney disease (CKD) is a growing problem among aging population, and the number of individuals at risk of end stage renal disease is rising. Part of the reason lies in incomplete understanding of the pathways underlying renal aging and kidney ... ...

Abstract	Chronic kidney disease (CKD) is a growing problem among aging population, and the number of individuals at risk of end stage renal disease is rising. Part of the reason lies in incomplete understanding of the pathways underlying renal aging and kidney disease, as well as insufficient delivery of evidence-based treatment to elderly patients with CKD. This review aims to address these unsolved issues by delineating updated mechanisms of renal senescence and summarizing recent findings on key clinical aspects of CKD in the elderly. Challenges and obstacles in caring for older people with CKD are discussed, with an emphasis on modification of risk factors, prevention of acute kidney injury, stabilization of progression and decision on dialysis initiation.
Language	English
Publishing date	2021-04-01
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2152-5250
ISSN	2152-5250
DOI	10.14336/AD.2020.0703
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Article: Predialysis trajectories of estimated GFR and concurrent trends of Chronic Kidney Disease-relevant biomarkers.

Tsao, Hsiao-Mei / Lai, Tai-Shuan / Chou, Yu-Hsiang / Lin, Shuei-Liong / Chen, Yung-Ming

Therapeutic advances in chronic disease

2023 Volume 14, Page(s) 20406223231177291

Abstract: Background: The glomerular filtration rate (GFR) decline varies in patients with advanced chronic kidney disease (CKD), and the concurrent changes in CKD-related biomarkers are unclear.: Objectives: This study aimed to examine the changes in CKD- ... ...

Abstract	Background: The glomerular filtration rate (GFR) decline varies in patients with advanced chronic kidney disease (CKD), and the concurrent changes in CKD-related biomarkers are unclear. Objectives: This study aimed to examine the changes in CKD-related biomarkers along with the kidney function decline in various GFR trajectory groups. Design: This study was a longitudinal cohort study originated from the pre-end-stage renal disease (pre-ESRD) care program in a single tertiary center between 2006 and 2019. Methods: We adopted a group-based trajectory model to categorize CKD patients into three trajectories according to estimated glomerular filtration rate (eGFR) changes. A repeated-measures linear mixed model was used to estimate the concurrent biomarker trends in a 2-year period before dialysis and to examine the differences among trajectory groups. A total of 15 biomarkers were analyzed, including urine protein, serum uric acid, albumin, lipid, electrolytes, and hematologic markers. Results: Using longitudinal data from 2 years before dialysis initiation, 1758 CKD patients were included. We identified three distinct eGFR trajectories: persistently low eGFR levels, progressive loss of eGFR, and accelerated loss of eGFR. Eight of the 15 biomarkers showed distinct patterns among the trajectory groups. Compared with the group with persistently low eGFR values, the other two groups were associated with a more rapid increase in the blood urea nitrogen (BUN) level and urine protein-creatinine ratio (UPCR), especially in the year before dialysis initiation, and a more rapid decline in hemoglobin and platelet counts. A rapid eGFR decline was associated with lower levels of albumin and potassium, and higher levels of mean corpuscular hemoglobin concentration (MCHC) and white blood cell (WBC). The albumin level in the group with an accelerated loss of eGFR was below the normal range. Conclusion: Using longitudinal data, we delineated the changes in CKD biomarkers with disease progression. The results provide information to clinicians and clues to elucidate the mechanism of CKD progression.
Language	English
Publishing date	2023-06-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2554816-5
ISSN	2040-6231 ; 2040-6223
ISSN (online)	2040-6231
ISSN	2040-6223
DOI	10.1177/20406223231177291
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Article: Muscle strength in ostensibly healthy non-diabetic subjects.

Wu, Ney-Min / Chiang, Chieh / Lin, Kun-Pei / Chen, Yung-Ming / Yang, Wei-Shiung

Journal of the Formosan Medical Association = Taiwan yi zhi

2023

Abstract: Background/purpose: Sarcopenia and decreased muscle strength (dynapenia) are emerging health issues. However, the study exploring muscle strength changes of both upper and lower limbs at the same time among all age groups is rare. This study aims to ... ...

Abstract	Background/purpose: Sarcopenia and decreased muscle strength (dynapenia) are emerging health issues. However, the study exploring muscle strength changes of both upper and lower limbs at the same time among all age groups is rare. This study aims to investigate the muscle strength and to establish a muscle strength norm of an ostensibly healthy non-diabetic Asian population. Methods: From 2018 June to 2020 March, subjects (aged from 20 to <80 years old) undergoing health checkup in Good Liver Medical Examination Center and National Taiwan University Hospital Geriatrics and Gerontology Department were enrolled. A battery of muscle power examinations including handgrip strength (HGS), five times sit-to-stand test (5TSTS), and one-leg standing test (OLST) were performed. Results: A total of 183 participants was enrolled, consisting of 92 females and 91 males. The finding shows the strongest HGS, best 5TSTS, and the longest OLST of both genders appeared in the 20-29-year-old group. Age, gender, and palm length are significantly related to HGS, whereas age is the only factor affecting 5TSTS and OLST. It revealed a progressive decline during ageing process, especially after age 60. Finally, Z-score and T-score norms of these were established. Conclusion: These data will be useful as normal controls for muscle strength of specific disease groups. The application of the cutoffs from these data and their comparisons with the recommended cutoffs from various guidelines worth further exploration.
Language	English
Publishing date	2023-11-15
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	2096659-3
ISSN	1876-0821 ; 0929-6646
ISSN (online)	1876-0821
ISSN	0929-6646
DOI	10.1016/j.jfma.2023.10.026
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Article: The journey from erythropoietin to 2019 Nobel Prize: Focus on hypoxia-inducible factors in the kidney.

Pan, Szu-Yu / Chiang, Wen-Chih / Chen, Yung-Ming

Journal of the Formosan Medical Association = Taiwan yi zhi

2020 Volume 120, Issue 1 Pt 1, Page(s) 60–67

Abstract: The 2019 Nobel Prize in Physiology or Medicine was awarded to William G. Kaelin Jr, Sir Peter J. Ratcliffe, and Gregg L. Semenza "for their discoveries of how cells sense and adapt to oxygen availability." The three pioneers discovered the hypoxia- ... ...

Abstract	The 2019 Nobel Prize in Physiology or Medicine was awarded to William G. Kaelin Jr, Sir Peter J. Ratcliffe, and Gregg L. Semenza "for their discoveries of how cells sense and adapt to oxygen availability." The three pioneers discovered the hypoxia-inducible factor (HIF), elucidated the oxygen sensing mechanism of cells, and confirmed the critical role of HIF in hypoxic cellular responses. The broad and profound biological effects of HIF open up the possibilities for clinical translation. HIF stabilizers have been proven effective on anemia of chronic kidney disease in phase III clinical trials. HIF antagonists for cancer treatment are under phase II clinical trials. It is imperative to gain insight into the biology of HIF. In this article, the discovery of HIF and its oxygen-dependent enzymatic regulation will be introduced, based largely on the groundbreaking work of the three Nobel laureates. Next, the biology of HIF in the kidney will be reviewed. Studies on the HIF stabilizers in the context of kidney disease, as well as the manipulation of HIF in different renal cell types will be covered. Lastly, the clinical application of HIF stabilizers and HIF antagonists for the treatment of anemia and cancer, respectively, will be discussed.
MeSH term(s)	Erythropoietin ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit ; Kidney ; Nobel Prize ; Oxygen
Chemical Substances	Hypoxia-Inducible Factor 1, alpha Subunit ; Erythropoietin (11096-26-7) ; Oxygen (S88TT14065)
Language	English
Publishing date	2020-06-17
Publishing country	Singapore
Document type	Journal Article ; Review
ZDB-ID	2096659-3
ISSN	1876-0821 ; 0929-6646
ISSN (online)	1876-0821
ISSN	0929-6646
DOI	10.1016/j.jfma.2020.06.006
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Article: Trends in the incidence and prevalence of end-stage kidney disease requiring dialysis in Taiwan: 2010-2018.

Lai, Tai-Shuan / Hsu, Chih-Cheng / Lin, Ming-Huang / Wu, Vin-Cent / Chen, Yung-Ming

Journal of the Formosan Medical Association = Taiwan yi zhi

2022 Volume 121 Suppl 1, Page(s) S5–S11

Abstract: Background/purpose: Taiwan has the highest incidence and prevalence of end-stage kidney disease (ESKD) worldwide. However, the epidemiologic features of ESKD requiring dialysis in Taiwan are unclear.: Methods: Our study population included all ... ...

Abstract	Background/purpose: Taiwan has the highest incidence and prevalence of end-stage kidney disease (ESKD) worldwide. However, the epidemiologic features of ESKD requiring dialysis in Taiwan are unclear. Methods: Our study population included all patients undergoing chronic dialysis (i.e., receiving dialysis treatment for at least three successive months) from the National Health Insurance Research Database from 2010 to 2018. Dialysis was defined using ICD-9-CM order codes for dialysis treatment. The age-standardized incidence and prevalence rates were calculated based on the World Health Organization standard population. Results: The mean age was 47.7 ± 15.4 years at dialysis initiation. The incidence of ESKD requiring dialysis increased steadily during the study period, whereas the age-standardized incidence rate remained constant. The increased rate was particularly prevalent in men aged 65-74 and 75+ years. Additionally, the percentage of patients with estimated glomerular filtration rates > 10 mL/min/1.73 m Conclusion: The annual incidence and prevalence of dialysis increased steadily from 2010 to 2018, whereas the age-standardized incidence and prevalence of dialysis remained stable. The increased numbers of patients undergoing incident and prevalent dialysis were mostly elderly, especially men aged ≥65 years. Age-based prevention strategies and multidisciplinary care should be implemented to target the elderly population at risk of developing ESKD.
MeSH term(s)	Adult ; Aged ; Humans ; Incidence ; Kidney Failure, Chronic/epidemiology ; Kidney Failure, Chronic/therapy ; Male ; Middle Aged ; Prevalence ; Renal Dialysis ; Taiwan/epidemiology
Language	English
Publishing date	2022-01-22
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	2096659-3
ISSN	1876-0821 ; 0929-6646
ISSN (online)	1876-0821
ISSN	0929-6646
DOI	10.1016/j.jfma.2021.12.013
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Article ; Online: Markers of Kidney Tubular Function Deteriorate While Those of Kidney Tubule Health Improve in Primary Aldosteronism After Targeted Treatments.

Wu, Vin-Cent / Chan, Chieh-Kai / Chueh, Jeff S / Chen, Yung-Ming / Lin, Yen-Hung / Chang, Chin-Chen / Lin, Po-Chih / Chung, Shiu-Dong

Journal of the American Heart Association

2023 Volume 12, Issue 4, Page(s) e028146

Abstract: Background Targeted treatment with mineralocorticoid receptor antagonists (MRAs) or adrenalectomy in patients with primary aldosteronism (PA) causes a decline in estimated glomerular filtration rate; however, the associated simultaneous changes in ... ...

Abstract	Background Targeted treatment with mineralocorticoid receptor antagonists (MRAs) or adrenalectomy in patients with primary aldosteronism (PA) causes a decline in estimated glomerular filtration rate; however, the associated simultaneous changes in biomarkers of kidney tubule health still remain unclear. Methods and Results We matched 104 patients with newly diagnosed unilateral PA who underwent adrenalectomy with 104 patients with unilateral PA who were treated with MRAs, 104 patients with bilateral PA treated with MRAs, and 104 patients with essential hypertension who served as controls. Functional biomarkers were measured before the targeted treatment and 1 year after treatment, including serum markers of kidney function (cystatin C, creatinine), urinary markers of proximal renal tubular damage (L-FABP [liver-type fatty-acid binding protein], KIM-1 [kidney injury molecule-1]), serum markers of kidney tubular reserve and mineral metabolism (intact parathyroid hormone), and proteinuria. Compared with the patients with essential hypertension, the patients with PA had higher pretreatment serum intact parathyroid hormone and urinary creatinine-corrected parameters, including L-FABP, KIM-1, and albumin. The patients with essential hypertension and with PA had similar cystatin C levels. After treatment with MRAs or adrenalectomy of unilateral PA and MRAs of bilateral PA, the patients with PA had increased serum cystatin C and decreased urinary L-FABP/creatinine, KIM-1/creatinine, creatinine-based estimated glomerular filtration rate, intact parathyroid hormone, and proteinuria (all
MeSH term(s)	Humans ; Cystatin C/metabolism ; Creatinine ; Kidney/metabolism ; Kidney Tubules ; Glomerular Filtration Rate/physiology ; Proteinuria/diagnosis ; Biomarkers ; Renal Insufficiency/metabolism ; Essential Hypertension/diagnosis ; Essential Hypertension/drug therapy ; Hyperaldosteronism/diagnosis ; Hyperaldosteronism/drug therapy ; Hyperaldosteronism/surgery ; Minerals
Chemical Substances	Cystatin C ; Creatinine (AYI8EX34EU) ; Biomarkers ; Minerals
Language	English
Publishing date	2023-02-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.122.028146
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Article ; Online: Unsupervised clustering identifies sub-phenotypes and reveals novel outcome predictors in patients with dialysis-requiring sepsis-associated acute kidney injury.

Lai, Chun-Fu / Liu, Jung-Hua / Tseng, Li-Jung / Tsao, Chun-Hao / Chou, Nai-Kuan / Lin, Shuei-Liong / Chen, Yung-Ming / Wu, Vin-Cent

Annals of medicine

2023 Volume 55, Issue 1, Page(s) 2197290

Abstract: Introduction: Heterogeneity exists in sepsis-associated acute kidney injury (SA-AKI). This study aimed to perform unsupervised consensus clustering in critically ill patients with dialysis-requiring SA-AKI.: Patients and methods: This prospective ... ...

Abstract	Introduction: Heterogeneity exists in sepsis-associated acute kidney injury (SA-AKI). This study aimed to perform unsupervised consensus clustering in critically ill patients with dialysis-requiring SA-AKI. Patients and methods: This prospective observational cohort study included all septic patients, defined by the Sepsis-3 criteria, with dialysis-requiring SA-AKI in surgical intensive care units in Taiwan between 2009 and 2018. We employed unsupervised consensus clustering based on 23 clinical variables upon initializing renal replacement therapy. Multivariate-adjusted Cox regression models and Fine-Gray sub-distribution hazard models were built to test associations between cluster memberships with mortality and being free of dialysis at 90 days after hospital discharge, respectively. Results: Consensus clustering among 999 enrolled patients identified three sub-phenotypes characterized with distinct clinical manifestations upon renal replacement therapy initiation ( Conclusions: Our data-driven approach suggests sub-phenotypes with clinical relevance in dialysis-requiring SA-AKI and serves an outcome predictor. This strategy represents further development toward precision medicine in the definition of high-risk sub-phenotype in patients with SA-AKI.Key messagesUnsupervised consensus clustering can identify sub-phenotypes of patients with SA-AKI and provide a risk prediction.Examining the features of patient heterogeneity contributes to the discovery of serum lactate levels ≥ 3.3 mmol/L upon initializing RRT as an independent outcome predictor.This data-driven approach can be useful for prognostication and lead to a better understanding of therapeutic strategies in heterogeneous clinical syndromes.
MeSH term(s)	Humans ; Prospective Studies ; Dialysis/adverse effects ; Retrospective Studies ; Acute Kidney Injury/etiology ; Acute Kidney Injury/therapy ; Phenotype ; Sepsis/complications ; Sepsis/therapy
Language	English
Publishing date	2023-04-11
Publishing country	England
Document type	Observational Study ; 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	10.1080/07853890.2023.2197290
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Article ; Online: Effect of isotemporal substitution of sedentary behavior with different intensities of physical activity on the muscle function of older adults in the context of a medical center.

Lai, Ting-Fu / Liao, Yung / Hsueh, Ming-Chun / Lin, Kun-Pei / Chan, Ding-Cheng / Chen, Yung-Ming / Wen, Chiung-Jung

BMC geriatrics

2023 Volume 23, Issue 1, Page(s) 130

Abstract: Background: Engaging in physical activity and reducing sedentary time in daily life may enable older individuals to maintain muscle mass. This study aimed to investigate the effects of replacing sedentary behavior with light physical activity (LPA) or ... ...

Abstract	Background: Engaging in physical activity and reducing sedentary time in daily life may enable older individuals to maintain muscle mass. This study aimed to investigate the effects of replacing sedentary behavior with light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on the muscle function of older adults at a medical center in Taiwan. Methods: We recruited 141 older adults (51.1% men; 81.1 ± 6.9 years old) and asked them to wear a triaxial accelerometer on the waist to measure their sedentary behavior and physical activity. Functional performance was assessed based on handgrip strength, Timed Up and Go (TUG) test, gait speed, and five-times-sit-to-stand test (5XSST). Isotemporal substitution analysis was performed to examine the effect of substituting 60 min of sedentary time with 60 min of LPA, MVPA, and combined LPA and MVPA in different proportions. Results: Reallocating 60 min of sedentary behavior per day to LPA was associated with better handgrip strength (Beta [B] = 1.587, 95% confidence interval [CI] = 0.706, 2.468), TUG test findings (B = -1.415, 95% CI = -2.186, -0.643), and gait speed (B = 0.042, 95% CI = 0.007, 0.078). Reallocating 60 min of sedentary behavior per day to MVPA was associated with better gait speed (B = 0.105, 95% CI = 0.018, 0.193) and 5XSST findings (B = -0.060, 95% CI = -0.117, -0.003). In addition, each 5-min increment in MVPA in the total physical activity replacing 60 min of sedentary behavior per day resulted in greater gait speed. Replacing 60 min of sedentary behavior with 30-min of LPA and 30-min of MVPA per day significantly decreased the 5XSST test time. Conclusion: Our study indicates that introducing LPA and a combination of LPA and MVPA to specifically replace sedentary behavior may help maintain muscle function in older adults.
MeSH term(s)	Male ; Humans ; Aged ; Aged, 80 and over ; Female ; Sedentary Behavior ; Hand Strength ; Exercise ; Hospitals ; Muscles
Language	English
Publishing date	2023-03-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2059865-8
ISSN	1471-2318 ; 1471-2318
ISSN (online)	1471-2318
ISSN	1471-2318
DOI	10.1186/s12877-023-03819-z
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Article ; Online: Age-Dependent Effects of Acute Kidney Injury on End-Stage Kidney Disease and Mortality in Patients with Moderate to Severe Chronic Kidney Disease.

Chou, Yu-Hsiang / Lai, Tai-Shuan / Lin, Yi-Chih / Chiang, Wen-Chih / Chu, Tzong-Shinn / Lin, Shuei-Liong / Chen, Yung-Ming

Nephron

2023 Volume 147, Issue 6, Page(s) 329–336

Abstract: Introduction: Old age has been considered as a positive modifier of chronic kidney disease (CKD), but the progression of CKD is often accelerated by acute kidney injury (AKI) in older adults. This study aimed to investigate this paradoxical interplay ... ...

Abstract	Introduction: Old age has been considered as a positive modifier of chronic kidney disease (CKD), but the progression of CKD is often accelerated by acute kidney injury (AKI) in older adults. This study aimed to investigate this paradoxical interplay and identify age-specific predictors of end-stage kidney disease (ESKD). Methods: This retrospective cohort included 6,101 patients with CKD stage 3B-5 followed at a single center during 2005-2018. Participants were stratified into four age groups to explore age-dependent influences on the risk of ESKD and all-cause mortality. Multivariate Cox proportional hazard regression model with competing risk analysis was used to identify predictors of outcomes. Results: During a median follow-up of 2.68 years, 1,650 (27.0%) patients developed ESKD and 541 (8.9%) patients died. The rate of ESKD decreased with advancing age, being lowest in the very old-aged (>75 years) group who displayed the slowest rate of estimated glomerular filtration rate (eGFR) decline. Multivariate Cox proportional hazard regression adjusted for competing death showed that younger ages, compared with patients aged >75 years, together with AKI episodes and several traditional risk factors were identified as predictors for ESKD. The impact of AKI episodes on ESKD development was most prominent in patients aged >75 years. These results were confirmed with subgroup analyses in patients with outcomes of different ages. Conclusion: Older adults with CKD exhibited a slower decline rate of eGFR, yet they were more likely to develop ESKD following AKI episodes. These results suggest tackling AKI is needed to prevent accelerated initiation of renal replacement therapy in elderly patients with pre-existing CKD.
MeSH term(s)	Aged ; Humans ; Middle Aged ; Retrospective Studies ; Disease Progression ; Kidney Failure, Chronic/therapy ; Renal Insufficiency, Chronic/therapy ; Glomerular Filtration Rate ; Acute Kidney Injury ; Risk Factors
Language	English
Publishing date	2023-01-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207121-6
ISSN	2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
ISSN (online)	2235-3186 ; 1423-0186
ISSN	1660-8151 ; 0028-2766
DOI	10.1159/000528021
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Article ; Online: Serum Urate and Risk of Chronic Kidney Disease: A Mendelian Randomization Study Using Taiwan Biobank.

Tsao, Hsiao-Mei / Lai, Tai-Shuan / Chang, Yi-Cheng / Hsiung, Chia-Ni / Chou, Yu-Hsiang / Wu, Vin-Cent / Lin, Shuei-Liong / Chen, Yung-Ming

Mayo Clinic proceedings

2023 Volume 98, Issue 4, Page(s) 513–521

Abstract: Objective: To evaluate the association between serum urate and risk of incident chronic kidney disease (CKD) and to assess whether serum urate plays a causal role in CKD.: Patients and methods: We conducted a prospective cohort study and Mendelian ... ...

Abstract	Objective: To evaluate the association between serum urate and risk of incident chronic kidney disease (CKD) and to assess whether serum urate plays a causal role in CKD. Patients and methods: We conducted a prospective cohort study and Mendelian randomization analysis that analyzed longitudinal data from the Taiwan Biobank between January 1, 2012, and December 31, 2021. Results: A total of 34,831 individuals met the inclusion criteria, of which 4697 (13.5%) had hyperuricemia. After a median (interquartile range) follow-up of 4.1 (3.1-4.9) years, 429 participants developed CKD. After adjustment for age, sex, and comorbid conditions, each mg/dL increase in serum urate was associated with a 15% higher risk of incident CKD (HR, 1.15; 95% CI, 1.08 to 1.24; P<.001). The genetic risk score and seven Mendelian randomization methods revealed no significant association between serum urate levels and the risk of incident CKD (HR, 1.03; 95% CI, 0.72 to 1.46; P=0.89; all P>.05 for 7 Mendelian randomization methods). Conclusion: This prospective, population-based cohort study showed that elevated serum urate is a significant risk factor for incident CKD; however, Mendelian randomization analyses failed to provide evidence that serum urate had a causal effect on CKD in the East Asian population.
MeSH term(s)	Humans ; Uric Acid ; Prospective Studies ; Cohort Studies ; Mendelian Randomization Analysis ; Biological Specimen Banks ; Taiwan ; Risk Factors ; Renal Insufficiency, Chronic
Chemical Substances	Uric Acid (268B43MJ25)
Language	English
Publishing date	2023-03-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	124027-4
ISSN	1942-5546 ; 0025-6196
ISSN (online)	1942-5546
ISSN	0025-6196
DOI	10.1016/j.mayocp.2023.01.004
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