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    Mai-szu Wu

    Background and Aims The substantial mortality and morbidity burden of chronic kidney disease (CKD) is well described, with the highest burden associated with progression to end-stage kidney disease (ESKD), where kidney replacement therapy... more
    Background and Aims The substantial mortality and morbidity burden of chronic kidney disease (CKD) is well described, with the highest burden associated with progression to end-stage kidney disease (ESKD), where kidney replacement therapy (dialysis or kidney transplantation) is indicated. CKD is known to have a detrimental effect on patient health-related quality of life (HRQoL). However, there is a lack of data comparing the impact of CKD on patient and caregiver HRQoL versus the general population. This study aimed to administer validated HRQoL instruments using a quantitative online survey to estimate the HRQoL of patients with CKD and their caregivers compared to the general population. Method A non-interventional survey enrolled adult patients with CKD and caregivers. Patients with a diagnosis of CKD for at least 3 months were included. ESKD was defined as patients with CKD stage 5 or receiving dialysis or a kidney transplant. Caregivers were required not to receive formal paym...
    The purpose of this phase I clinical trial is to assess the safety and tolerability of allogeneic adipose tissue-derived stem cells (ADSCs) among chronic kidney disease (CKD) patients. 12 eligible CKD patients with an estimated glomerular... more
    The purpose of this phase I clinical trial is to assess the safety and tolerability of allogeneic adipose tissue-derived stem cells (ADSCs) among chronic kidney disease (CKD) patients. 12 eligible CKD patients with an estimated glomerular filtration rate (eGFR) of 15-44 ml/min/1.73 m2 received one dose of intravenous allogeneic ADSCs (ELIXCYTE® ), as 3 groups: 3 low dose (6.4 × 107 cells in total of 8 ml), 3 middle dose (19.2 × 107 cells in total of 24 ml) and 6 high dose (32.0 × 107 cells in total of 40 ml) of ELIXCYTE® and evaluated after 48 weeks. Primary endpoint was the safety profiles in terms of incidence of adverse events (AEs) and serious adverse event (SAE). Two subjects in high dose group experienced a total of 2 treatment-related AEs which are Grade 1 slow speech and Grade 1 bradyphrenia after the infusion. One subject in middle dose group experienced an SAE unlikely related to treatment, grade 2 proteinuria. No fatal AE was reported in this study. An increase in eGFR was observed in 7 out of 12 subjects (58%) at Week 24 and in 6 of 12 subjects (50%) by Week 48. By Week 24, an increase in eGFR by more than 20% among all CKD patients with baseline eGFR ≧ 30 ml/min/1.73 m2 as compared to only 2 subjects in baseline eGFR < 30 ml/min/1.73 m2  group. No significant reduction in proteinuria was noted among all subjects. This phase I trial demonstrated single-dose intravenous ELIXCYTE was well tolerated in moderate-to-severe CKD patients and its preliminary efficacy warrants future studies.
    Background: The malnutrition-inflammation score (MIS) is an indicator of malnutrition-inflammation complex syndrome and an outcome predictor in maintenance hemodialysis patients. However, its utility in peritoneal dialysis (PD) patients... more
    Background: The malnutrition-inflammation score (MIS) is an indicator of malnutrition-inflammation complex syndrome and an outcome predictor in maintenance hemodialysis patients. However, its utility in peritoneal dialysis (PD) patients and its association with the Charlson comorbidity index (CCI) have not yet been examined. Methods: All chronic stable PD outpatients in the PD center of the National Taiwan University Hospital in January 2006 were studied and followed for up to 18 months. The baseline MIS and CCI at the beginning of the study and the dates and causes of mortality or hospitalization during the study period were obtained. Results: A total of 141 PD patients were enrolled. During the study period, 8 patients died and 40 patients had at least one fatal or nonfatal major cardiovascular or infection event. The CCI correlated positively and significantly with the MIS (r = +0.344, p < 0.001). The MIS and CCI were both independent predictors of cardiovascular and infection...
    In Taiwan, most first-time dialysis was started without the creation of an arteriovenous shunt. Here, we aimed to elucidate the transitions of dialysis status in the unplanned first dialysis patients and determine factors associated with... more
    In Taiwan, most first-time dialysis was started without the creation of an arteriovenous shunt. Here, we aimed to elucidate the transitions of dialysis status in the unplanned first dialysis patients and determine factors associated with their outcomes. A total of 50,315 unplanned first dialysis patients aged more than 18 years were identified from the National Health Insurance Dataset in Taiwan between 2001 and 2012. All patients were followed for 5 years for the transitions in dialysis status, including robust (dialysis-free), sporadic dialysis, continued dialysis, and death. Furthermore, factors associated with the development of continued dialysis and death were examined by the Cox proportional hazard models. After 5 years after the first dialysis occurrence, there were 5.39% with robust status, 1.67% with sporadic dialysis, 8.45% with continued dialysis, and 84.48% with death. Notably, we have identified common risk factors for developing maintenance dialysis and deaths, includ...
    This retrospective study aimed to investigate the effect of diabetes mellitus (DM) on the risks of end-stage kidney disease (ESKD) and post-liver transplantation (post-LT) mortality. Using data from the National Health Insurance Research... more
    This retrospective study aimed to investigate the effect of diabetes mellitus (DM) on the risks of end-stage kidney disease (ESKD) and post-liver transplantation (post-LT) mortality. Using data from the National Health Insurance Research Database, Taiwan, 3,489 patients who received a LT between 1 January 2005, and 31 December 2015, were enrolled in this study and divided into the pre-existing DM, post-LT DM (PLTDM), and without DM groups. All subjects were followed up from 1 year after LT to the index date for ESKD, and the occurrence of death, or until 31 December 2016. Of the 3,489 patients with LT, 1,016 had pre-existing DM, 215 had PLTDM, and 2,258 had no DM pre- or post-LT. The adjusted HRs of ESKD were 1.77 (95% Confidence Interval [CI], .78–3.99) and 2.61 (95% CI, 1.63–4.18) for PLTDM group and pre-existing DM group compared to without DM group, respectively. For the risk of death, the adjusted HRs were 1.05 (95% CI, .72–1.55) and 1.28 (95% CI, 1.04–1.59) for PLTDM group and...
    ObjectivesOver the past two decades, debates on whether the profit status of dialysis facilities influences patient prognosis have been popular in the USA. Taiwan is one of the regions with the highest rate per capita of kidney... more
    ObjectivesOver the past two decades, debates on whether the profit status of dialysis facilities influences patient prognosis have been popular in the USA. Taiwan is one of the regions with the highest rate per capita of kidney replacement therapy worldwide, but no similar research has been conducted to date. This is the first study to address this issue.DesignThis was a nationwide retrospective cohort study based on the Taiwan Renal Registry Data System.SettingPatients were categorised into two groups based on the profit status (for-profit, not-for-profit (NFP)) of dialysis facilities, with 31 350 patients in each group. The patients were followed up from 2005 to 2012.ParticipantsPatients with uraemia who underwent long-term haemodialysis in private dialysis facilities and public facilities were excluded.Primary and secondary outcome measuresSurvival analyses were performed to compare prognosis between the two groups. Adjustments to patients’ basic profile, and facilities’ geograph...
    Objective. The association between Polycystic Kidney Disease (PKD) and susceptibility to developing oncogenicity states remains controversial, and no consensus has yet been reached. Large-scale studies on this association are also... more
    Objective. The association between Polycystic Kidney Disease (PKD) and susceptibility to developing oncogenicity states remains controversial, and no consensus has yet been reached. Large-scale studies on this association are also lacking. Therefore, we identified the risk of developing cancer in PKD patients. Methods. Patients diagnosed with PKD between 2000 and 2010 were enrolled in the National Health Insurance Research Database (NHIRD)-derived Longitudinal Health Insurance. Patients with antecedent cancer, end-stage renal disease, or those diagnosed with cancer within one year were excluded. Using a Standardized Incidence Ratio (SIR), we compared the patterns of cancer incidence in PKD patients and the general population. Results. The entire cohort was observed for 8,014 people, and a total of 1820 PKD patients were included, and after a median follow-up of 4.43 years, 82 patients developed cancer. Though the risk of overall cancers was comparable between PKD patients and the ge...
    OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease... more
    OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30–5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin–angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%. RESULTS...
    Background: Psychological depression and physical disability are closely correlated in hemodialysis patients. A retrospective cohort study was conducted to examine the independent association of physical and psychological functioning with... more
    Background: Psychological depression and physical disability are closely correlated in hemodialysis patients. A retrospective cohort study was conducted to examine the independent association of physical and psychological functioning with mortality in a hemodialysis cohort in Taiwan. Methods: A total of 888 stable hemodialysis patients were included. Patients completed two questionnaires: the 36-item Short Form Health Survey Questionnaire (SF-36, Taiwan Standard Version 1.0) and the Beck Depression Inventory (BDI, Chinese Version). Mortality outcomes were recorded for a seven-year follow-up period. Results: There were 303 deaths recorded. BDI scores were inversely related to all health-related quality of life (HRQoL) domains (p < 0.001). In the Cox-proportional hazard model, only poor physical dimension of HRQoL was independently associated with higher mortality. Conclusion: Poor physical dimension in HRQoL is a strong predictor of mortality among hemodialysis patients in Taiwan....
    Background We explored the long-term safety and efficacy of ferric citrate in hemodialysis patients in Taiwan, and further evaluated the iron repletion effect and change of iron parameters by different baseline groups. Methods This was a... more
    Background We explored the long-term safety and efficacy of ferric citrate in hemodialysis patients in Taiwan, and further evaluated the iron repletion effect and change of iron parameters by different baseline groups. Methods This was a 12-month, Phase IV, multicenter, open-label study. The initial dose of ferric citrate was administered by patients’ clinical condition and further adjusted to maintain serum phosphorus at 3.5–5.5 mg/dL. The primary endpoint was to assess the safety profiles of ferric citrate. The secondary endpoints were to evaluate the efficacy by the time-course changes and the number of subjects who achieved the target range of serum phosphorus. Results A total of 202 patients were enrolled. No apparent or unexpected safety concerns were observed. The most common treatment-emergent adverse events were gastrointestinal-related with discolored feces (41.6%). Serum phosphorus was well controlled, with a mean dose of 3.35±1.49 g/day, ranging from 1.5 to 6.0 g/day. Ir...
    BACKGROUND: The prevalence and incidence of end-stage renal disease are high in Taiwan. Acute leptospirosis infection often causes renal tubulointerstitial disease, but the association of occult leptospirosis and renal disease is unclear.... more
    BACKGROUND: The prevalence and incidence of end-stage renal disease are high in Taiwan. Acute leptospirosis infection often causes renal tubulointerstitial disease, but the association of occult leptospirosis and renal disease is unclear. The aim of this study is to define the possible association between occult leptospirosis infection and chronic kidney disease (CKD). METHODS: In this prospective observational cohort study, 371 patients with CKD and 100 residents without CKD in the same community were included. Microscopic agglutination test (MAT) was employed to detect occult leptospirosis. Both renal progression and microalbuminuria were also monitored during a follow-up period of 42 months. RESULTS: Low prevalence of positive MAT is found in normal and CKD subjects. There was no significant difference in amount of microalbuminuria between MAT positive and negative subjects (527.52 ± 125.18 vs. 728.2 ± 216.23, mg/day, P > 0.05). Logistic analysis for CKD progression did not show ...
    We report a case of tuberculous peritonitis in a chronic peritoneal dialysis patient with unusual initial presentations of painless and neutrophil predominant dialysate. The patient was a 63-year-old female under chronic perironeal... more
    We report a case of tuberculous peritonitis in a chronic peritoneal dialysis patient with unusual initial presentations of painless and neutrophil predominant dialysate. The patient was a 63-year-old female under chronic perironeal dialysis for 2 years. She was admitted to our hospital because of intermittent fever with chills, anorexia and periumbilical abdominal fullness for two weeks. Routine dialysate examination revealed increased leukocyte count in dialysate with neutrophil predominant. MRI and laparoscope c examination found peritoneal cysts. Direct smear of the peritoneal effluent revealed acid-fast bacilli. Peritoneal fluid culture revealed mycobacteria tuberculosis. Due to persistent peritonitis and ultrafiltration inadequacy, the Tenckhoff catheter was removed and renal replacement therapy was shifted to chronic hemodialysis. We presented painless neutrophil-predominant mnycobacteria peritonitis in a patient under chronic peritoneal dialysis. The rare presentations of the...
    Background and objectivesChronic kidney disease (CKD) is a global public health issue associated with large economic burdens. CKD contributes to higher risks of cardiovascular complications, kidney failure, and mortality. The incidence... more
    Background and objectivesChronic kidney disease (CKD) is a global public health issue associated with large economic burdens. CKD contributes to higher risks of cardiovascular complications, kidney failure, and mortality. The incidence and prevalence rates of kidney failure in Taiwan have remained the highest in the world.Design, setting, participants, & measurementsAssessing genetic factors that influence kidney function in specific populations has substantial clinical relevance. We investigated associations of genetic variants with eGFR. The quality control filtering and genotype imputation resulted in 10,008 Taiwan Biobank participants and 6,553,511 variants for final analyses. We examined these loci within silicoreplication in individuals of European and African ancestry.ResultsOur results revealed one significant locus (4q21.1) and three suggestive significant loci (17q23.2, 22q13.2, and 3q29) for eGFR in the Taiwanese population. In total, four conditional-independent single n...
    Aging contributes to the progression of vascular dysfunction and is a major nonreversible risk factor for cardiovascular disease. The aim of this study was to determine the effectiveness of using arterial pulse-wave measurements,... more
    Aging contributes to the progression of vascular dysfunction and is a major nonreversible risk factor for cardiovascular disease. The aim of this study was to determine the effectiveness of using arterial pulse-wave measurements, frequency-domain pulse analysis, and machine-learning analysis in distinguishing vascular aging. Radial pulse signals were measured noninvasively for 3 min in 280 subjects aged 40-80 years. The cardio-ankle vascular index (CAVI) was used to evaluate the arterial stiffness of the subjects. Forty frequency-domain pulse indices were used as features, comprising amplitude proportion (Cn), coefficient of variation of Cn, phase angle (Pn), and standard deviation of Pn (n = 1-10). Multilayer perceptron and random forest with supervised learning were used to classify the data. The detected differences were more prominent in the subjects aged 40-50 years. Several indices differed significantly between the non-vascular-aging group (aged 40-50 years; CAVI <9) and the vascular-aging group (aged 70-80 years). Fivefold cross-validation revealed an excellent ability to discriminate the two groups (the accuracy was >80%, and the AUC was >0.8). For subjects aged 50-60 and 60-70 years, the detection accuracies of the two trained algorithms were around 80%, with AUCs of >0.73 for both, which indicated acceptable discrimination. The present method of frequency-domain analysis may improve the index reliability for further machine-learning analyses of the pulse waveform. The present noninvasive and objective methodology may be meaningful for developing a wearable-device system to reduce the threat of vascular dysfunction induced by vascular aging.
    Identifying modifiable risk factors of peritoneal dialysis (PD)-related peritonitis is of clinical importance in patient care. Mineral bone disease (MBD) has been associated with mortality and morbidity in end-stage kidney disease (ESKD)... more
    Identifying modifiable risk factors of peritoneal dialysis (PD)-related peritonitis is of clinical importance in patient care. Mineral bone disease (MBD) has been associated with mortality and morbidity in end-stage kidney disease (ESKD) patients. However, its influence on PD related peritonitis due to altered host immunity remains elusive. This study investigated whether abnormal biomarkers of MBD are associated with the development of peritonitis in patients undergoing maintenance PD. We conducted a retrospective observational cohort study, analysing data derived from a nationwide dialysis registry database in Taiwan, from 2005 to 2012. A total of 5750 ESKD patients commencing PD therapy during this period were enrolled and followed up to 60 months or by the end of the study period. The patients were stratified based on their baseline serum parathyroid hormone (PTH) levels, calcium (Ca) levels or phosphorus (P) levels, respectively or in combinations. The primary outcome was the o...
    Background and Aims Introduction: Chronic kidney disease (CKD) patients are known to have greater risk of urothelial cancer (UC) than general population. Urine is the most non-invasive examination and is directly linked to UC. Urinalysis... more
    Background and Aims Introduction: Chronic kidney disease (CKD) patients are known to have greater risk of urothelial cancer (UC) than general population. Urine is the most non-invasive examination and is directly linked to UC. Urinalysis and urine cytology are the major screening tools; however, these tests have low sensitivity or specificity in early disease. In this study, we used both normal and Non-UC CKD patients as controls to discover novel and more specific protein biomarkers in urine for early UC diagnosis. Aims To discover novel and more specific urinary protein biomarkers for screening of urothelial cancer (UC) in CKD patients. Method This is a multicenter prospective cohort study, carried out at 10 nationwide hospitals covering different regions of Taiwan from 2013-2018. Subjects were Taiwanese healthy adults (healthy controls, n=210), patients with CKD but without UC (disease controls, n=273) and patients with ongoing UC (n=211). For non-UC patients, urine and blood spe...
    Introduction: End-stage kidney disease (ESKD) patients who need renal replacement therapy need to face a dialysis modality decision: the choice between hemodialysis (HD) and peritoneal dialysis (PD). Although the global differences in... more
    Introduction: End-stage kidney disease (ESKD) patients who need renal replacement therapy need to face a dialysis modality decision: the choice between hemodialysis (HD) and peritoneal dialysis (PD). Although the global differences in HD/PD penetration are affected by health-care policies, these two modalities may exert different effects on survival in patients with ESKD. Although Taiwan did not implicate PD as first policy, we still need to compare patients’ outcomes using two modalities in a nation-wise database to determine future patients’ care and health policies. Methods: We used the nationwide Taiwan Renal Registry Data System (TWRDS) database from 2005 to 2012 and included 52,900 patients (48,371 on HD and 4529 on PD) to determine all-cause and cardiovascular mortality among ESKD patients. Results: Age-matched survival probability from all-cause mortality was significantly lower in patients on PD than in those on HD (p < 0.05). The adjusted hazard ratios of 3-year and 5-y...
    Laxatives are commonly prescribed for constipation management; however, they are recognized as an independent factor associated with cardiovascular diseases. Arteriovenous fistula (AVF) is the closest to the ideal model of hemodialysis... more
    Laxatives are commonly prescribed for constipation management; however, they are recognized as an independent factor associated with cardiovascular diseases. Arteriovenous fistula (AVF) is the closest to the ideal model of hemodialysis (HD) vascular access and part of the cardiovascular system. Our study aims to explore the association of contact laxative use with AVF maturation outcomes in patients undergoing HD. We conducted a multi-center cohort study of 480 contact laxative users and 472 non-users who had undergone initial AVF creation. All patients were followed until the outcomes of AVF maturation were confirmed. Multivariable logistic regression models were performed to evaluate the risk of AVF maturation failure imposed by laxatives. Here, we found that patients who used contact laxatives were significantly associated with an increased risk of AVF maturation failure compared to non-users (adjusted odds ratio, 1.64; p = 0.003). Notably, the risk of AVF maturation failure incr...
    Background Only few studies with inconsistent results comparing the relative risk of cardiac mortality between peritoneal dialysis (PD) and hemodialysis (HD). Switches between renal replacement therapy (RRT) modalities render objective... more
    Background Only few studies with inconsistent results comparing the relative risk of cardiac mortality between peritoneal dialysis (PD) and hemodialysis (HD). Switches between renal replacement therapy (RRT) modalities render objective assessment of survival benefits a greater challenge. Methods Data were retrieved from Taiwan’s National Health Insurance Database from 1 January 2006 to 31 December 2015. We included 13 662 and 41 047 long-term dialysis patients in a propensity score matching study design and a time-varying study design, respectively, to compare major adverse cardiovascular events (MACEs) between patients receiving PD and HD. We also included 109 256 dialysis patients to compare the all-cause mortality among different RRT modalities. Results For MACE, the hazard ratio (HR) for PD patients compared to HD patients was 0.95 [95% confidence interval (CI) 0.89–1.02] in the propensity score study design and 1.06 (95% CI 1.01–1.12) in the time-varying study design. For all-c...
    Renal diseases impose considerable health and economic burdens on health systems worldwide, and there is a lack of efficient methods for the prevention and treatment due to their complexity and heterogeneity. Kidneys are organs with a... more
    Renal diseases impose considerable health and economic burdens on health systems worldwide, and there is a lack of efficient methods for the prevention and treatment due to their complexity and heterogeneity. Kidneys are organs with a high demand for energy produced by mitochondria, in which Rrm2b has critical functions as reported. The Rrm2b kidney-specific knockout mice we generated exhibited age-dependent exacerbated features, including mitochondrial dysfunction and increased oxidative stress; additionally, resulted in severe disruption of mitochondria-related metabolism. Rrm2b is vital not only to supply dNTPs for DNA replication and repair, but also to maintain structural integrity and metabolic homeostasis in mitochondria. Thence, Rrm2b deletion might induce chronic kidney defects in mice. This model can facilitate exploration of novel mechanisms and targeted therapies in the kidney diseases and has important translational and clinical implications.
    Acute kidney disease (AKD) comprises acute kidney injury (AKI). However, whether the AKD staging system has prognostic values among AKI patients with different baseline estimated glomerular filtration (eGFR) remains a controversial issue.... more
    Acute kidney disease (AKD) comprises acute kidney injury (AKI). However, whether the AKD staging system has prognostic values among AKI patients with different baseline estimated glomerular filtration (eGFR) remains a controversial issue. Algorithm-based approach was applied to identify AKI occurrence and to define different AKD stages. Risk ratio for major adverse kidney events (MAKE), including (1) eGFR decline > 35% from baseline, (2) initiation of dialysis, (3) in-hospital mortality of different AKD subgroups were identified by multivariable logistic regression. Among the 4741 AKI patients identified from January 2015 to December 2018, AKD stages 1–3 after AKI was common (53% in the lower baseline eGFR group and 51% in the higher baseline eGFR group). In the logistic regression model adjusted for demographics and comorbidities at 1-year follow-up, AKD stages 1/2/3 (AKD stage 0 as reference group) were associated with higher risks of MAKE (AKD stage: odds ratio, 95% confidence...
    We have previously demonstrated calcimimetics optimize the balance between osteoclastic bone resorption and osteoblastic mineralization through upregulating Wingless and int-1 (Wnt) signaling pathways in the mouse and cell model.... more
    We have previously demonstrated calcimimetics optimize the balance between osteoclastic bone resorption and osteoblastic mineralization through upregulating Wingless and int-1 (Wnt) signaling pathways in the mouse and cell model. Nonetheless, definitive human data are unavailable concerning therapeutic effects of Cinacalcet on chronic kidney disease and mineral bone disease (CKD-MBD) and osteoclast–osteoblast interaction. We aim to investigate whether Cinacalcet therapy improves bone mineral density (BMD) through optimizing osteocytic homeostasis in a human model. Hemodialysis patients with persistently high intact parathyroid hormone (iPTH) levels > 300 pg/mL for more than 3 months were included and received fixed dose Cinacalcet (25 mg/day, orally) for 6 months. Bone markers presenting osteoclast–osteoblast communication were evaluated at baseline, the 3rd and the 6th month. Eighty percent of study patients were responding to Cinacalcet treatment, capable of improving BMD, T sc...
    Periodontitis and chronic kidney disease are both chronic inflammatory diseases and share some common risk factors. This 3-month pilot study aimed to clarify whether non-surgical periodontal therapy is beneficial in clinical, biochemical,... more
    Periodontitis and chronic kidney disease are both chronic inflammatory diseases and share some common risk factors. This 3-month pilot study aimed to clarify whether non-surgical periodontal therapy is beneficial in clinical, biochemical, and microbiological conditions in patients with periodontitis and kidney failure. Kidney failure patients with moderate to severe periodontitis were recruited from two hospitals. Treatment group received non-surgical periodontal therapy, and control group received oral hygiene instruction only. Outcome assessments were conducted 1 and 3 months after treatment. Non-parametric tests were used to analyze the patient-level data. Periodontal site-level assessments were analyzed by Student t-test and paired t-test. Statistical significance was set at p-value < 0.05. A total of 11 subjects completed the study. There was no significant difference between groups in all-cause mortality, cardiovascular events, infection events, systemic parameters, and ser...
    Immunoglobulin G (IgG) N-glycosylation was discovered to have an association with inflammation status, which has the potential to be a novel biomarker for kidney diseases. In this study, we applied an ultra-high performance liquid... more
    Immunoglobulin G (IgG) N-glycosylation was discovered to have an association with inflammation status, which has the potential to be a novel biomarker for kidney diseases. In this study, we applied an ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method to plasma and urine samples from 57 individuals with different levels of kidney function. Natural abundances of total IgG, IgG1, IgG2, and IgG3 subclasses in plasma showed positive correlations to the estimated glomerular filtration rates (eGFRs). Eighteen IgG glycopeptides also showed positive correlations. In contrast, higher IgG amounts were found in urine samples from participants with lower eGFR values. After normalizing IgG glycopeptides from plasma to their respective protein amounts, H4N4F1S1-IgG1 (r = 0.37, p = 0.0047, significant) and H5N4F1S1-IgG1 (r = 0.25, p = 0.063, marginally significant) were the two glycopeptides that still had positive correlations with eGFRs. The results showed...
    High dietary phosphate intake and poor adherence to phosphate-binding-therapy elevate the risk of hyperphosphatemia in maintenance hemodialysis (HD; MHD) patients. Therefore, chronic kidney disease-related mineral and bone disorder... more
    High dietary phosphate intake and poor adherence to phosphate-binding-therapy elevate the risk of hyperphosphatemia in maintenance hemodialysis (HD; MHD) patients. Therefore, chronic kidney disease-related mineral and bone disorder (CKD-MBD) indicators increase; consequently, risks of CKD-MBDs and inflammation are elevated. This double-blind, randomized control trial intervention study was designed to investigate the possibility of reducing blood CKD-MBD indicators and modulating inflammatory indicators by consuming low-phosphate (LP) meals accompanied by a minimum dose of a calcium-based phosphate binder (CaCO3). MHD patients were recruited and randomly assigned to an LP meal group (LP group) or a control group. After initial data collection, blood collection, and dietary counseling, subjects were asked to consume a washout diet for 1 week. During the washout diet period, subjects consumed their usual diet but took 1 tablet of calcium carbonate (1CaCO3) as a phosphate binder with e...
    Previously, we successfully developed an extracorporeal endotoxin removal device (EERD) that is based on the novel next generation alternating microtube array membrane (MTAM-A) that was superior to the commercial equivalent. In this... more
    Previously, we successfully developed an extracorporeal endotoxin removal device (EERD) that is based on the novel next generation alternating microtube array membrane (MTAM-A) that was superior to the commercial equivalent. In this article, we demonstrated multiple different parameter modifications that led to multiple different types of novel new MTAM structures, which ultimately led to the formation of the MTAM-A. Contrary to the single layered MTAM, the MTAM-A series consisted of a superior packing density fiber connected in a double layered, alternating position which allowed for the greater fiber count to be packed per unit area. The respective MTAM variants were electrospun by utilizing our internally developed tri-axial electrospinning set up to produce the novel microstructures as seen in the respective MTAM variants. A key uniqueness of this study is the ability to produce self-arranged fibers into the respective MTAM variants by utilizing a single spinneret, which has not...
    Low-osmolality carbohydrate–electrolyte solution (LCS) ingestion can replace losses from exercise-induced dehydration, but the benefits of LCS ingestion strategy after exhaustive endurance exercise (EEE) remain unknown. The present study... more
    Low-osmolality carbohydrate–electrolyte solution (LCS) ingestion can replace losses from exercise-induced dehydration, but the benefits of LCS ingestion strategy after exhaustive endurance exercise (EEE) remain unknown. The present study evaluated the effects of LCS ingestion on dehydration, oxidative stress, renal function, and aerobic capacity after EEE. In our study with its double-blind, crossover, counterbalanced design, 12 healthy male participants were asked to consume LCS (150 mL four times per hour) or placebo (water) 1 h before and 1 h after EEE. All participants completed a graded exercise test to exhaustion on a treadmill for the determination of maximal oxygen consumption ( V ˙ O 2 max ), applied to further intensity calibration, and then completed the EEE test. The average heart rate, maximal heart rate, running time to exhaustion, and peak oxygen uptake (VO2peak) were recorded during the exercise period. The participants’ body weight was recorded at different time poi...
    Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the drug hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal... more
    Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the drug hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal necrolysis. The adverse events are unpredictable and carry significant morbidity and mortality. To identify genetic markers for allopurinol–SCAR, we carried out a case-control association study. We enrolled 51 patients with allopurinol–SCAR and 228 control individuals (135 allopurinol-tolerant subjects and 93 healthy subjects from the general population), and genotyped for 823 SNPs in genes related to drug metabolism and immune response. The initial screen revealed strong association between allopurinol–SCAR and SNPs in the MHC region, including BAT3 (encoding HLA-B associated transcript 3), MSH5 (mutS homolog 5), and MICB (MHC class I polypeptide-related sequence B) ( P < 10 –7 ). We then determined the alleles of HLA loci A, B, C, and DRB1. The H...
    Abnormalities in mineral metabolism are common complications of organ transplantation. The role of immunosuppressive agents in alteration of mineral metabolism is not clear. We conducted an animal study to investigate the effects of... more
    Abnormalities in mineral metabolism are common complications of organ transplantation. The role of immunosuppressive agents in alteration of mineral metabolism is not clear. We conducted an animal study to investigate the effects of cyclosporine A (CsA), tacrolimus, and sirolimus on renal calcium, magnesium and vitamin D metabolism. CsA and tacrolimus induced a 2- to 3-fold and 1.6- to 1.8-fold increase in urinary calcium and magnesium excretion, respectively, while rapamycin had no effects on calcium, but doubled the urinary magnesium excretion. CsA and tacrolimus, but not rapamycin, elevated serum 1,25(OH)(2) vitamin D without affecting the parathyroid hormone level. CsA and tacrolimus reduced mRNA abundance in TRPV5 (CsA: 64 ± 3% of control; tacrolimus: 50 ± 3%) calbindin-D28k (CsA: 62 ± 4%; tacrolimus: 43 ± 3%), and vitamin D receptor (CsA: 52 ± 3%; tacrolimus: 58 ± 2%, all p < 0.05). Rapamycin did not affect gene expression in any of studied proteins. The immunofluorescence staining study demonstrated a 50% reduction of TRPV5 and calbindin-D28k by CsA and tacrolimus. The suppression of VDR by calcineurin inhibitors is probably the underlying mechanism of renal calcium wasting. In spite of an increased 1,25(OH)(2) vitamin D level, the kidney is not able to reserve calcium, suggesting a role of vitamin D resistance that may be related to bone loss.
    Hypoxemia and obstructive sleep apnea (OSA) have been recognized as a threat to life. Nonetheless, information regarding the association between pre-dialytic pulse oximeter saturation (SpO2) level, OSA and mortality risks remains... more
    Hypoxemia and obstructive sleep apnea (OSA) have been recognized as a threat to life. Nonetheless, information regarding the association between pre-dialytic pulse oximeter saturation (SpO2) level, OSA and mortality risks remains mysterious in patients with maintenance hemodialysis (MHD). Bioclinical characteristics and laboratory features were recorded at baseline. Pre-dialytic SpO2 was detected using a novel microchip LED oximetry, and the Epworth Sleepiness Scale (ESS) score greater than 10 indicated OSA. Non-adjusted and adjusted hazard ratios (aHRs) of all-cause and cardiovascular (CV) mortality were analyzed for pre-dialytic SpO2, OSA and potential risk factors. During 2152.8 patient-months of follow-up, SpO2 was associated with incremental risks of all-cause and CV death (HR: 0.90 (95% CI: 0.82–0.98) and 0.88 (95% CI: 0.80–0.98), respectively). The association between OSA and CV mortality was significant (HR: 3.19 (95% CI: 1.19–9.38). In the multivariate regression analysis, ...

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