Publications by authors named "Mei-Yi Wu"

80 Publications

Periodontal disease and risk of mortality and kidney function decline in advanced chronic kidney disease: a nationwide population-based cohort study.

Clin Oral Investig 2021 Apr 4. Epub 2021 Apr 4.

Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, No. 291, Zhongzheng Rd., Zhonghe District, New Taipei City, 23561, Taiwan.

Objectives: Periodontal disease is prevalent in patients with chronic kidney disease (CKD) and potentially associated with kidney function decline. However, it is uncertain whether periodontal disease affects the risk of mortality and morbidity in patients with advanced CKD.

Materials And Methods: Taiwan's National Health Insurance Research Database was used to conduct a nationwide population-based cohort study. Propensity score matching procedures were performed to select people with stage 5 CKD and to compare the long-term risk of mortality, end-stage renal disease, and major adverse cardiovascular events (MACE) between people with and without periodontal disease. Multivariable Cox regression analyses were conducted to calculate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the outcome of interest.

Results: A total of 8119 subjects with stage 5 CKD were initially included. After matching to demographic and clinical covariates, 1254 subjects with 7099 person-years of follow-up were selected for analyses. Periodontal disease was not associated with long-term risks of all-cause mortality (aHR: 0.77, 95% CI: 0.49-1.22), progression to end-stage renal disease (aHR: 0.91, 95% CI: 0.75-1.10), or MACE (aHR: 1.18, 95% CI: 0.91-1.53). These findings were generally consistent across subgroups of age, sex, comorbid diabetes, uses of systemic antibiotic, and different dental procedures.

Conclusions: Periodontal disease is not a predictor for long-term mortality or morbidity in patients with advanced CKD.

Clinical Relevance: These results provide important evidence to elucidate the relationship between periodontitis and critical clinical outcomes of advanced CKD.
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http://dx.doi.org/10.1007/s00784-021-03924-6DOI Listing
April 2021

Influenza vaccination reduces incidence of peripheral arterial occlusive disease in elderly patients with chronic kidney disease.

Sci Rep 2021 Mar 1;11(1):4847. Epub 2021 Mar 1.

Department of Primary Care Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.

An influenza vaccination might reduce the risk of incident peripheral arterial occlusive disease (PAOD) in patients with chronic kidney disease (CKD), but supporting evidence is limited. This case-crossover study analyzed data from Taiwan's real-world National Health Insurance Research Database. This study included elderly (≥ 67 years old) patients with CKD having incident PAOD from January 1, 2006, to June 30, 2015. We defined 1 year before PAOD onset as the index date for the self-control group. A conditional logistic regression model was used to investigate exposure to an influenza vaccination for estimating the risk for incident PAOD following vaccination. In total, this study included 46,782 elderly patients with CKD having incident PAOD. The odds ratios for incident PAOD were 0.85 (95% confidence interval 0.77-0.94), 0.85 (0.79-0.92), 0.84 (0.79-0.90), and 0.85 (0.81-0.90) at 1, 2, 3, and 4 months after an influenza vaccination, respectively. We observed consistent results for the subgroups of patients with CKD and concomitant diabetes. However, we did not observe any beneficial effects of influenza vaccination in patients with advanced CKD or end-stage renal disease. This study demonstrated that influenza vaccination may be associated with a reduced risk of incident PAOD among patients with early-stage CKD.
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http://dx.doi.org/10.1038/s41598-021-84285-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921588PMC
March 2021

Sugar- and artificially-sweetened beverages and the risks of chronic kidney disease: a systematic review and dose-response meta-analysis.

J Nephrol 2021 Jan 27. Epub 2021 Jan 27.

Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City, 235, Taiwan.

Background: Consumption of sugar or artificially-sweetened beverages (SASBs) has been linked to albuminuria, decline in kidney function, and risk of chronic kidney disease (CKD). However, the results are controversial. We therefore aim to evaluate the effects of sugar or artificially-sweetened beverage consumption on CKD risk.

Methods: Original observational studies reporting relative risks (RRs) with 95% confidence intervals (CIs) for the association between sugar or artificially-sweetened beverage consumption and impaired renal function or CKD risk in adults were identified using a systematic search of PubMed and EMBASE from inception to 20 February, 2019. Random effects model was applied to derive summary RRs and 95% CIs. Linear and non-linear dose-response relationships were estimated using data from sugar or artificially-sweetened beverage consumption categories in each study.

Results: The summary RR of CKD for high versus low sugar-sweetened beverage consumption was 1.30 (95% CI 0.88-1.94) according to six included studies with a total of 25,455 participants, while the pooled RR of CKD for high versus low artificially sweetened beverage consumption was 1.40 (95% CI 0.65-3.02) according to three studies with a total of 19,995 participants. For dose-response analysis, a significant, increased risk of CKD was observed with the sugar or artificially-sweetened beverage consumption above seven servings per week (P < 0.001).

Conclusion: Our study found a positive association between consumption of sugar or artificially-sweetened beverage consumption and CKD, though it did not reach statistical significance. However, the dose-response results suggest that more than seven servings per week should be avoided.
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http://dx.doi.org/10.1007/s40620-020-00957-0DOI Listing
January 2021

Aberrant serum parathyroid hormone, calcium, and phosphorus as risk factors for peritonitis in peritoneal dialysis patients.

Sci Rep 2021 Jan 13;11(1):1171. Epub 2021 Jan 13.

Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.

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 occurrence of first episode of peritonitis, and patient outcomes such as deaths, transfer to haemodialysis or receiving renal transplantation were censored. Peritonitis-free survival and the influence of PTH, Ca, P (individual or in combination) on the peritonitis occurrence were analysed. A total of 5750 PD patients was enrolled. Of them, 1611 patients experienced their first episode of peritonitis during the study period. Patients with low PTH, high Ca or low P levels, respectively or in combination, had the lowest peritonitis-free survival. After adjusting for age, sex and serum albumin levels, we found that the combinations of low PTH levels with either high Ca levels or low/normal P levels were significant risk factors of developing peritonitis. Abnormal mineral bone metabolism in maintenance PD patients with low serum PTH levels, in combination with either high Ca levels or low/normal P levels, could be novel risk factors of PD-related peritonitis.
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http://dx.doi.org/10.1038/s41598-020-80938-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806837PMC
January 2021

Long-term Clinical Outcome of Major Adverse Vascular Events After Hypertensive Disorders of Pregnancy.

Obstet Gynecol 2021 02;137(2):285-293

Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, the Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, the Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung City, the Division of Gastroenterology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, the Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, the Emergency Department, Shuang Ho Hospital, Taipei Medical University, New Taipei City, the Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, Taipei, the Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, the Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, and the Department of Dentistry and Department of Medical Research, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.

Objective: To assess the association between hypertensive disorders of pregnancy and adverse events after pregnancy, including chronic kidney disease and major adverse cardiovascular events (cerebrovascular accident, coronary artery disease, or death).

Methods: A nationwide, population-based cohort study was conducted analyzing women with hypertensive disorders of pregnancy identified from Taiwan National Health Insurance Research Database from 2004 to 2015. Hypertensive disorders of pregnancy were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. The study cohort was comprised of women aged 20-40 years diagnosed with hypertensive disorders of pregnancy from 2006 to 2013. The comparison group comprised of four randomly selected women without hypertensive disorders of pregnancy, matched for age and index date for each woman with hypertensive disorders of pregnancy. All the women were followed from the date of cohort entry until they developed chronic kidney disease or major adverse cardiovascular events or until the end of 2015, whichever occurred first. A Cox proportional hazard model was used to estimate the risk of chronic kidney disease and major adverse cardiovascular events.

Results: We identified 29,852 women with a diagnosis of hypertensive disorders of pregnancy and 119,408 matched women without hypertensive disorders of pregnancy who fit the inclusion criteria. The crude hazard ratios (HRs) were 5.22 (95% CI 4.67-5.83) and 2.26 (95% CI 1.99-2.57) for chronic kidney disease and major adverse cardiovascular events. After adjusting for potential confounders, hypertensive disorders of pregnancy was associated with a higher risk of chronic kidney disease (adjusted HR, 4.26; 95% CI 3.80-4.78), and major adverse cardiovascular events (adjusted HR, 2.15; 95% CI 1.89-2.45).

Conclusion: This population-based cohort study indicated that women with hypertensive disorders of pregnancy are at a higher risk of chronic kidney disease and major adverse cardiovascular events than women without hypertensive disorders of pregnancy. Further studies are required to clarify the nature of these associations and to improve public health interventions.
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http://dx.doi.org/10.1097/AOG.0000000000004277DOI Listing
February 2021

Resuscitation fluid types in sepsis, surgical, and trauma patients: a systematic review and sequential network meta-analyses.

Crit Care 2020 12 14;24(1):693. Epub 2020 Dec 14.

Institute of Epidemiology and Preventive Medicine, National Taiwan University, Room 539, No. 17, Xu-Zhou Rd., Taipei, 10055, Taiwan.

Background: Crystalloids and different component colloids, used for volume resuscitation, are sometimes associated with various adverse effects. Clinical trial findings for such fluid types in different patients' conditions are conflicting. Whether the mortality benefit of balanced crystalloid than saline can be inferred from sepsis to other patient group is uncertain, and adverse effect profile is not comprehensive. This study aims to compare the survival benefits and adverse effects of seven fluid types with network meta-analysis in sepsis, surgical, trauma, and traumatic brain injury patients.

Methods: Searched databases (PubMed, EMBASE, and Cochrane CENTRAL) and reference lists of relevant articles occurred from inception until January 2020. Studies on critically ill adults requiring fluid resuscitation were included. Intervention studies reported on balanced crystalloid, saline, iso-oncotic albumin, hyperoncotic albumin, low molecular weight hydroxyethyl starch (L-HES), high molecular weight HES, and gelatin. Network meta-analyses were conducted using random-effects model to calculate odds ratio (OR) and mean difference. Risk of Bias tool 2.0 was used to assess bias. Confidence in Network Meta-Analysis (CINeMA) web application was used to rate confidence in synthetic evidence.

Results: Fifty-eight trials (n = 26,351 patients) were identified. Seven fluid types were evaluated. Among patients with sepsis and surgery, balanced crystalloids and albumin achieved better survival, fewer acute kidney injury, and smaller blood transfusion volumes than saline and L-HES. In those with sepsis, balanced crystalloids significantly reduced mortality more than saline (OR 0.84; 95% CI 0.74-0.95) and L-HES (OR 0.81; 95% CI 0.69-0.95) and reduced acute kidney injury more than L-HES (OR 0.80; 95% CI 0.65-0.99). However, they required the greatest resuscitation volume among all fluid types, especially in trauma patients. In patients with traumatic brain injury, saline and L-HES achieved lower mortality than albumin and balanced crystalloids; especially saline was significantly superior to iso-oncotic albumin (OR 0.55; 95% CI 0.35-0.87).

Conclusions: Our network meta-analysis found that balanced crystalloids and albumin decreased mortality more than L-HES and saline in sepsis patients; however, saline or L-HES was better than iso-oncotic albumin or balanced crystalloids in traumatic brain injury patients.

Trial Registration: PROSPERO website, registration number: CRD42018115641).
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http://dx.doi.org/10.1186/s13054-020-03419-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734863PMC
December 2020

Impact of dialysis modality on major adverse cardiovascular events and all-cause mortality: a national population-based study.

Nephrol Dial Transplant 2020 Dec 12. Epub 2020 Dec 12.

Department of Internal Medicine, Division of Nephrology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.

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-cause mortality, the HR for PD patients compared to HD patients was 1.09 (95% CI 1.05-1.13) in the propensity score study design and 1.13 (95% CI 1.09-1.17) in the time-varying study design. The HR for death was higher at a level of statistical significance for females (1.21, 95% CI 1.15-1.28), patients ≥65 years old (1.30, 95% CI 1.24-1.36) and diabetes mellitus (DM; 1.28, 95% CI 1.22-1.34).

Conclusions: The HR for MACE is significantly higher among PD patients in time-varying design analysis. In addition, all-cause mortality was higher in PD patients compared to patients with HD, especially in those who were aged ≥65 years, female or DM.
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http://dx.doi.org/10.1093/ndt/gfaa282DOI Listing
December 2020

Therapeutic Effect of Calcimimetics on Osteoclast-Osteoblast Crosslink in Chronic Kidney Disease and Mineral Bone Disease.

Int J Mol Sci 2020 Nov 18;21(22). Epub 2020 Nov 18.

Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.

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 score and Z score (16.4%, 20.7% and 11.1%, respectively). A significant correlation between BMD improvement and iPTH changes was noted ( = -0.26, < 0.01). Nonetheless, baseline lower iPTH level was associated with better responsiveness to Cinacalcet therapy. Sclerostin, an inhibitor of canonical Wnt/β-catenin signaling, was decreased from 127.3 ± 102.3 pg/mL to 57.9 ± 33.6 pg/mL. Furthermore, Wnt-10b/Wnt 16 expressions were increased from 12.4 ± 24.2/166.6 ± 73.3 pg/mL to 33.8 ± 2.1/217.3 ± 62.6 pg/mL. Notably, procollagen type I amino-terminal propeptide (PINP), a marker of bone formation and osteoblastic activity, was increased from baseline 0.9 ± 0.4 pg/mL to 91.4 ± 42.3 pg/mL. In contrast, tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), a marker of osteoclast activity, was decreased from baseline 16.5 ± 0.4 mIU/mL to 7.7 ± 2.2 mIU/mL. Moreover, C-reactive protein levels were suppressed from 2.5 ± 0.6 to 0.8 ± 0.5 mg/L, suggesting the systemic inflammatory burden may be benefited after optimizing the parathyroid-bone axis. In conclusion, beyond iPTH suppression, our human model suggests Cinacalcet intensifies BMD through inhibiting sclerostin expression and upregulating Wnt-10b/Wnt 16 signaling that activates osteoblastic bone formation and inhibits osteoclastic bone resorption and inflammation. From the perspective of translation to humans, this research trial brings a meaningful insight into the osteoblast-osteoclast homeostasis in Cinacalcet therapy for CKD-MBD.
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http://dx.doi.org/10.3390/ijms21228712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698938PMC
November 2020

Association of Variants with Reduced Kidney Function in Patients with Diabetic Kidney Disease.

J Pers Med 2020 Nov 6;10(4). Epub 2020 Nov 6.

Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.

Diabetic kidney disease (DKD) is the leading cause of morbidity and mortality in patients with diabetes mellitus (DM) and the most common variant of end-stage renal disease (ESRD) globally. The economic burden of ESRD treatment with dialysis is substantial. The incidence and prevalence of ESRD in Taiwan remain the highest worldwide. Therefore, identifying genetic factors affecting kidney function would have valuable clinical implications. We performed microarray experiments and identified that ubiquitin protein ligase E3C () is differentially expressed in two DKD patient groups with extreme (low and high) urine protein-to-creatinine ratios. A follow-up genotyping study was performed in a larger group to investigate any specific variants of associated with DKD. A total of 263 patients were included in the study, comprising 172 patients with DKD and 91 control subjects (patients with DM without chronic kidney disease (CKD)). Two variants (rs3802129(AA) and rs7807(CC)) were determined to be associated with reduced kidney function. The haplotype analysis revealed that rs3802129/rs3815217 (block 1) with A/G haplotype and rs8101/rs7807 (block 2) with T/C haplotype were associated with higher risks of CKD phenotypes. These findings suggest a clinical role of variants in DKD risk.
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http://dx.doi.org/10.3390/jpm10040210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712123PMC
November 2020

Radio-contrast medium exposure and dialysis risk in patients with chronic kidney disease and congestive heart failure: A case-only study.

Int J Cardiol 2021 Feb 12;324:199-204. Epub 2020 Sep 12.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan. Electronic address:

Background: Dialysis for end stage renal disease is considered a major public health challenge. Pre-existing chronic kidney disease (CKD) and congestive heart failure (CHF) may be independent risk factors for contrast-induced acute kidney injury. The aim of this study is to investigate dialysis risk in patients with CKD and CHF after radio-contrast medium exposure or coronary catheterization.

Method: This case-crossover design used the Health Insurance Database to identify incident dialysis patients with CKD and CHF. Patients themselves in 6 months ago serve as their own controls. This prevents selection bias in the control group, such as healthy volunteer bias and confounding bias. Conditional logistic regression model was used to estimate the risk of dialysis shortly after radio-contrast medium exposure.

Results: In total, 36,709 patients with CKD and CHF underwent dialysis after radio-contrast medium exposure. At 1 week, the odds ratio (OR) for dialysis was 4.49 (95% Confidence Interval: 3.99-5.05). The ORs for acute-temporary (N = 23,418) and chronic dialysis (N = 13,291) were 5.57 (4.83-6.42) and 2.37 (1.90-2.95) after radio-contrast medium exposure, respectively. The ORs for dialysis after radio-contrast medium exposure in advanced CKD patients (N = 12,030) were 3.25 (2.53-4.19) and 4.85 (4.24-5.54) in early CKD patients (N = 24,679). The ORs for dialysis after coronary catheterization in patients with CKD and CHF was 3.75 (2.57-5.48).

Conclusions: In this study, the clinical risk for acute-temporary or chronic dialysis was significantly high when the bias was fully considered. We need strategies to reduce the subsequent risk of dialysis after radio-contrast medium exposure, especially in patients with CKD and CHF.
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http://dx.doi.org/10.1016/j.ijcard.2020.09.014DOI Listing
February 2021

Prognostic Effect of Comorbid Disease and Immune Gene Expression on Mortality in Kidney Cancer-A Population Based Study.

Cancers (Basel) 2020 Jun 22;12(6). Epub 2020 Jun 22.

Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei City 110, Taiwan.

The effect of comorbidities and the immune profiles of the kidney cancer microenvironment play a major role in patients' prognosis and survival. Using the National Health Insurance Research Database (Taiwan), we identified patients aged >20 years with a first diagnosis of kidney cancer between 2005 and 2014. Differences in demographic characteristics and comorbidities were examined using the Pearson chi-squared test or the t test. The Cox regression model was used to construct the nomogram. RNA-seq data were applied from The Cancer Genome Atlas database, and correlations between immune metagenes and clinical characteristics were determined using a linear regression model. In this nationwide cohort study, including 5090 patients with kidney cancer, predictors in our prediction models included age, sex, chronic kidney disease, dialysis requirements, renal stones, cerebrovascular disease, and metastasis tumor. In the tumor tissue profiles, significant positive correlations between immune metagenes and clinical stage or overall survival were observed among Natural Killer (NK) cells (CD56-), CD4+ T-helper 2 (Th2) cells, and activated Dendritic Cell (aDC). A negative correlation was observed between expression level of Dendritic Cell (DC) and overall survival. Patients with kidney cancer exhibit high prevalence of comorbid disease, especially in older patients. Comorbid disease types exert unique effects, and a particular comorbidity can affect cancer mortality. Moreover, the expression of immune metagenes can be utilized as potentialbiomarkers especially for further study of molecular mechanisms as well as microenvironments in kidney cancer.
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http://dx.doi.org/10.3390/cancers12061654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352532PMC
June 2020

Combined effect of polymorphisms of MTHFR and MTR and arsenic methylation capacity on developmental delay in preschool children in Taiwan.

Arch Toxicol 2020 06 21;94(6):2027-2038. Epub 2020 Apr 21.

Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are related to cognitive dysfunction and mental disability. These genes, along with folate and vitamin B levels, are regulators of one-carbon metabolism, which synthesizes S-adenosylmethionine (SAM) as a methyl donor for arsenic methylation. The aim of this study was to explore whether polymorphisms of MTHFR and MTR influence arsenic methylation capacity and plasma folate and vitamin B levels and if these influences cause developmental delay in preschool children. A total of 178 children with developmental delay and 88 without developmental delay were recruited from August 2010 to March 2014. A high-performance liquid chromatography-hydride generator and atomic absorption spectrometer were used to determine urinary arsenic species. Plasma folate and vitamin B concentrations were measured by SimulTRAC-SNB radioassay. Polymorphisms of MTHFR C677T, MTHFR A1298C, and MTR A2756G were examined by polymerase chain reaction and restriction fragment length variation. The results show that MTHFR C677T C/T and T/T genotypes had a lower risk of developmental delay than the C/C genotype (odds ratio [OR] = 0.47; 95% confidence interval, 0.26-0.85). Subjects with the MTHFR C677T C/C genotype had significantly lower plasma folate and vitamin B levels than those with the MTHFR C677T C/T and T/T genotype. The MTHFR C677T C/C genotype combined with high total urinary arsenic and poor arsenic methylation capacity indices significantly increased the OR of developmental delay in a dose-response manner. This is the first study to show the combined effect of MTHFR C677T genotype and poor arsenic methylation capacity on developmental delay.
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http://dx.doi.org/10.1007/s00204-020-02745-yDOI Listing
June 2020

Comparing the Efficacy of OnabotulinumtoxinA, Sacral Neuromodulation, and Peripheral Tibial Nerve Stimulation as Third Line Treatment for the Management of Overactive Bladder Symptoms in Adults: Systematic Review and Network Meta-Analysis.

Toxins (Basel) 2020 02 18;12(2). Epub 2020 Feb 18.

Division of Urology, Department of Surgery, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei 23142, Taiwan.

The American Urological Association guidelines for the management of non-neurogenic overactive bladder (OAB) recommend the use of OnabotulinumtoxinA, sacral neuromodulation (SNM), and peripheral tibial nerve stimulation (PTNS) as third line treatment options with no treatment hierarchy. The current study used network meta-analysis to compare the efficacy of these three modalities for managing adult OAB syndrome. We performed systematic literature searches of several databases from January 1995 to September 2019 with language restricted to English. All randomized control trials that compared any dose of OnabotulinumtoxinA, SNM, and PTNS with each other or a placebo for the management of adult OAB were included in the study. Overall, 17 randomized control trials, with a follow up of 3-6 months in the predominance of trials (range 1.5-24 months), were included for analysis. For each trial outcome, the results were reported as an average number of episodes of the outcome at baseline. Compared with the placebo, all three treatments were more efficacious for the selected outcome parameters. OnabotulinumtoxinA resulted in a higher number of complications, including urinary tract infection and urine retention. Compared with OnabotulinumtoxinA and PTNS, SNM resulted in the greatest reduction in urinary incontinence episodes and voiding frequency. However, comparison of their long-term efficacy was lacking. Further studies on the long-term effectiveness of the three treatment options, with standardized questionnaires and parameters are warranted.
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http://dx.doi.org/10.3390/toxins12020128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077313PMC
February 2020

Association between air pollutants and development of chronic kidney disease: A systematic review and meta-analysis.

Sci Total Environ 2020 Mar 16;706:135522. Epub 2019 Nov 16.

Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Integrated Diagnostics & Therapeutics, National Taiwan University College of Medicine, Taipei, Taiwan; Institute of Food Safety and Health, National Taiwan University, Taipei, Taiwan. Electronic address:

Background: The association between incident chronic kidney disease (CKD) or end-stage renal disease (ESRD) and exposure to outdoor air pollution is under debate. We aimed to examine this relationship based on a systematic review with random-effects meta-analysis.

Methods: We screened the literature on long-term air pollution exposure assessment in the general population using an electronic search of PubMed, Medline, Embase, and Cochrane Library from inception to 20 October 2019. Observational studies investigating the association between long-term exposure to gaseous (CO, SO, NO, O) or particulate (PM or PM) outdoor air pollutants and CKD, ESRD, or renal dysfunction were included, and summary risks were estimated.

Results: Of 4419 identified articles, 23 met our inclusion criteria after screening and 14 were included in the meta-analysis. Pooled effect estimates had the following summary risk ratios (RRs) for CKD: 1.10 (95% confidence intervals [CI] 1.00, 1.21; derived from four studies) per 10 μg/m increase in PM and 1.16 (95% CI 1.05, 1.29; derived from four studies) for PM; 1.31 (95% CI 0.86, 2.00; derived from two studies) per 10 ppm increase in CO; and 1.11 (95% CI 1.09, 1.14; derived from three studies) per 10 ppb increase in NO. For the pooled effect on eGFR, increases in PM and PM (of 10 μg/m) were associated with eGFR decline by -0.83 (95% CI -1.54, -0.12; derived from two studies) and -4.11 (95% CI -12.64, 4.42; derived from two studies) mL/min/1.73 m, respectively.

Conclusions: Air pollution was observed to be associated with CKD and renal function decline. Although more longitudinal studies are required, we argue that air pollution is pernicious to kidney health.
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http://dx.doi.org/10.1016/j.scitotenv.2019.135522DOI Listing
March 2020

Quantitative determination of human IgA subclasses and their Fc-glycosylation patterns in plasma by using a peptide analogue internal standard and ultra-high-performance liquid chromatography/triple quadrupole mass spectrometry.

Rapid Commun Mass Spectrom 2020 Apr 8;34 Suppl 1:e8606. Epub 2020 Feb 8.

Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Rationale: Glycosylation on immunoglobulins is important for the immune function. In this study, we developed and validated a method for the absolute quantification of IgA subclasses and relative quantification of IgA-Fc glycopeptides by using affinity purification and ultrahigh-performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS). Only micro-volumes of plasma were required from each sample and we also applied the method to discover IgA and IgA-glycopeptide profiles in patients with chronic kidney diseases and IgA nephropathy.

Methods: Peptide M affinity beads were used to purify IgA, and a cost-effective peptide analogue was added as internal standard. With an efficient on-bead digestion process, purified samples were analyzed by UHPLC/MS/MS in multiple reaction monitoring mode.

Results: Correlation coefficients were greater than 0.999 for the IgA1 and IgA2 calibration curves and greater than 0.994 for glycopeptide regression curves. Intraday and interday precisions for IgA1 and IgA2 were <1.6% and <5.1% RSD, respectively. Intraday and interday accuracies ranged from 102.6 to 114.9% and 103.5 to 113.5% for IgA1 and IgA2, respectively. Stabilities of IgA1 and IgA2 at -80°C for 7 to 15 days ranged from 96.0 to 109.4%, respectively. The Pearson's correlation coefficient was 0.916 when comparing the IgA quantification results of the 30 clinical samples by using ELISAs and the developed UHPLC/MS/MS method. Compared with healthy controls, IgA and IgA-glycopeptides showed different profiles in patients with chronic kidney diseases and IgA nephropathy.

Conclusions: The developed method showed good validation results, and the absolute quantification results of IgA correlated with those from ELISA. The pilot application study showed that IgA and IgA-glycopeptides can be potential biomarker candidates for kidney diseases, and more clinical sample applications are worth investigating.
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http://dx.doi.org/10.1002/rcm.8606DOI Listing
April 2020

Effects and Safety of an Oral Adsorbent on Chronic Kidney Disease Progression: A Systematic Review and Meta-Analysis.

J Clin Med 2019 Oct 17;8(10). Epub 2019 Oct 17.

Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.

Background: AST-120 (Kremezin), which is an oral spherical carbon adsorbent, has been reported to have the potential for retarding disease progression in patients with chronic kidney disease. We aimed to evaluate its efficacy and safety in this study.

Methods: We systematically searched for randomized controlled trials published in PubMed, Embase, and Cochrane databases. The primary outcomes were the renal outcome and all-cause mortality, and the change in serum indoxyl sulfate (IS) levels. The safety outcome was also evaluated in terms of reported major adverse events. A random-effects model was used when heterogeneity was expected.

Results: Eight studies providing data for 3349 patients were included in the meta-analysis. The risk ratio of renal outcome and all-cause mortality were 0.97 (95% CI: 0.88-1.07; 6 trials) and 0.94 (0.73-1.20; 5 trials), respectively. Furthermore, the weighted mean change in IS levels from baseline to the end of the study was -0.28 mg/dL (95% CI: -0.46 to -0.11; 4 trials).

Conclusions: This study provides evidence that AST-120 can effectively lower IS levels but still controversial in terms of slowing disease progression and all-cause mortality. Except for dermatological events, the incidence of adverse events did not differ significantly between the AST-120 and placebo groups.
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http://dx.doi.org/10.3390/jcm8101718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832608PMC
October 2019

Use of mammalian target of rapamycin inhibitors in patient with autosomal dominant polycystic kidney disease: an updated meta-analysis.

Int Urol Nephrol 2019 Nov 1;51(11):2015-2025. Epub 2019 Oct 1.

Department of Nephrology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.

Purpose: Mammalian target of rapamycin (mTOR) inhibitors were previously considered a potential therapy for autosomal dominant polycystic kidney disease (ADPKD), but prior studies remained controversial about their efficacy. We performed an updated meta-analysis regarding the therapeutic and adverse effects of mTOR inhibitors in patients with ADPKD.

Methods: We systematically searched Cochrane Library, PubMed, EMBASE, and Medline for randomized controlled trials (RCTs) comparing mTOR inhibitors to placebo in ADPKD patients up to August 2019. We calculated weighted mean differences (WMDs) for total kidney volume (TKV), estimated glomerular filtration rates (eGFRs), and weighted odds ratios (ORs) for treatment-related complications between the treatment and the placebo groups, using the random effects model.

Results: We retrieved a total of 9 RCTs enrolling 784 ADPKD patients receiving rapamycin, sirolimus, or everolimus between 2009 and 2016. The WMDs of TKV and eGFR from baseline to the last measurement were - 31.54 mL (95% confidence interval [CI] - 76.79 to 13.71 mL) and 2.81 mL/min/1.73 m (95% CI - 1.85 to 7.46 mL/min/1.73 m), respectively. Patients receiving mTOR inhibitors had a significantly increased risk of any adverse effects (OR 5.92, 95% CI 3.53-9.94), with the most common ones being aphthous stomatitis (OR 15.45, 95% CI 9.68-24.66) and peripheral edema (OR 3.49, 95% CI 1.31-9.27) compared to placebo users.

Conclusions: mTOR inhibitors did not significantly influence renal progression in patients with ADPKD, but were associated with a higher risk of complications. Whether mTOR inhibitors can be an add-on option or second-line agents remain undetermined.
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http://dx.doi.org/10.1007/s11255-019-02292-1DOI Listing
November 2019

Identification of the PTEN-ARID4B-PI3K pathway reveals the dependency on ARID4B by PTEN-deficient prostate cancer.

Nat Commun 2019 09 24;10(1):4332. Epub 2019 Sep 24.

Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC, 20037, USA.

PTEN is frequently mutated in prostate cancer. The tumor suppressor function of PTEN is attributed to its lipid phosphatase activity that counters PI3K action. Here, we report a PTEN-ARID4B-PI3K axis in which PTEN inhibits expression of ARID4B, while ARID4B is a transcriptional activator of the PI3K subunit genes PIK3CA and PIK3R2 that are crucial for activation of the PI3K/AKT pathway. Reciprocal binding of ARID4B and histone H1 to the PIK3CA and PIK3R2 promoters modulates chromatin condensation, suggesting a mechanism by which ARID4B activates these promoters. Functional analyses reveals that ARID4B is required for prostate tumorigenesis when PTEN is deficient. The biological significance is further substantiated by the existence of a PTEN/ARID4B/PIK3CA three-gene signature that improves the predictive power for prostate cancer recurrence in patients. In summary, we identify ARID4B as a master regulator in the PTEN-PI3K pathway, thus providing a potential therapeutic target for prostate cancer carrying PTEN mutations.
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http://dx.doi.org/10.1038/s41467-019-12184-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760172PMC
September 2019

Association of plasma folate, vitamin B12 levels, and arsenic methylation capacity with developmental delay in preschool children in Taiwan.

Arch Toxicol 2019 09 31;93(9):2535-2544. Epub 2019 Aug 31.

Department of Family Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.

Developmental delay has been associated with inefficient arsenic methylation capacity in preschool children. Folate and vitamin B12 are important nutrients that produce s-adenosylmethionine during single-carbon metabolism and provide methyl groups for arsenic methylation. The aim of the present study was to explore whether plasma folate and vitamin B12 levels influence arsenic methylation capacity and in turn are related to developmental delay in preschool children. A case-control study was conducted in 178 children with developmental delay and 88 normal children, who were recruited from Shin Kong Wu Ho-Su Memorial Teaching Hospital from August 2010 to March 2014. Arsenite (As), arsenate (As), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in the urine was determined by high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Plasma folate and vitamin B12 levels were measured using a SimulTRAC-SNB radioassay. The results show that the combination of high plasma folate and high vitamin B12 levels were correlated with efficient arsenic methylation capacity (low MMA %, low InAs %, and high DMA %). High MMA % significantly increased and high DMA % and secondary methylation index decreased the odds ratio (OR) of developmental delay in a dose-dependent manner in both low plasma folate and low vitamin B12 (low/low) groups; the multivariate OR and 95% confidence interval were 5.01 (0.83-30.06), 0.21 (0.04-1.23), and 0.20 (0.03-1.20), respectively. This is the first study to show that the combination of high plasma folate and high vitamin B12 levels increases arsenic methylation capacity and indirectly decreases the OR of developmental delay in preschool children.
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http://dx.doi.org/10.1007/s00204-019-02540-4DOI Listing
September 2019

Effects of febuxostat on renal function in patients with chronic kidney disease: A systematic review and meta-analysis.

Medicine (Baltimore) 2019 Jul;98(29):e16311

Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital.

Background/objective: Hyperuricemia has been proven to be an independent risk factor for chronic kidney disease (CKD). However, the role of hyperuricemia in the progression of CKD remains unclear. Thus, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of febuxostat, a first line urate-lowering agent, in CKD patients with hyperuricemia.

Methods: We have systematically searched for randomized controlled trials assessing the efficacy and safety of febuxostat versus control in CKD patients with hyperuricemia through MEDLINE, PubMed, EMBASE, and Cochrane databases. All statistical analyses were conducted by using the statistical package Review Manager, version 5.3.5. Heterogeneity was assessed using the Cochrane Q and I tests and summary statistics were reported with 95% confidence interval. Two-tailed test was used for analysis and a P value of <.05 is considered statistically significant.

Results: Eleven eligible trials with 1317 participants were included in the meta-analysis. A significant reduction in serum uric acid was found in the febuxostat treated group. Also, a significant higher eGFR was found in the febuxostat treated group among CKD stage 3 and 4 patients. No significant difference of major complication or death was identified between treatment and control groups.

Conclusions: The meta-analysis showed that other than its urate-lowering effect, febuxostat presented a reno-protective effect in CKD patients. More studies with larger sample sizes and higher quality are required to clarify the role of febuxostat use in the progression of CKD.
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http://dx.doi.org/10.1097/MD.0000000000016311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709169PMC
July 2019

The Kidney Clock Contributes to Timekeeping by the Master Circadian Clock.

Int J Mol Sci 2019 Jun 5;20(11). Epub 2019 Jun 5.

Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei 11031, Taiwan.

The kidney harbors one of the strongest circadian clocks in the body. Kidney failure has long been known to cause circadian sleep disturbances. Using an adenine-induced model of chronic kidney disease (CKD) in mice, we probe the possibility that such sleep disturbances originate from aberrant circadian rhythms in kidney. Under the CKD condition, mice developed unstable behavioral circadian rhythms. When observed in isolation in vitro, the pacing of the master clock, the suprachiasmatic nucleus (SCN), remained uncompromised, while the kidney clock became a less robust circadian oscillator with a longer period. We find this analogous to the silencing of a strong slave clock in the brain, the choroid plexus, which alters the pacing of the SCN. We propose that the kidney also contributes to overall circadian timekeeping at the whole-body level, through bottom-up feedback in the hierarchical structure of the mammalian circadian clocks.
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http://dx.doi.org/10.3390/ijms20112765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600447PMC
June 2019

Association of endothelin genetic variants and hospitalized infection complications in end-stage renal disease (ESRD) patients.

BMC Nephrol 2019 06 5;20(1):203. Epub 2019 Jun 5.

Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.

Background: Infection is the second most common cause of mortality for patients with end-stage renal disease (ESRD), accompanying with immune dysfunction. Endothelin (EDN) is known to be related to inflammation; however, it is unknown whether genetic variants of the EDN gene family are associated with increased risk of hospitalized infection events.

Methods: Nineteen tagging single-nucleotide polymorphisms (tSNPs) of the EDN gene family were selected for genotyping a cohort of 190 ESRD patients. Patient demographics were recorded, the subtypes of infection events were identified, and association analysis between the EDN genetic variants and hospitalized infection events was performed.

Results: In this study, 106 patients were hospitalized for infection events. The leading events were pneumonia, bacteremia, and cellulitis. The minor allele of rs260741, rs197173, and rs926632 SNPs of EDN3 were found to be associated with reduced risk of hospitalized bacteremia events.

Conclusions: The minor allele of rs260741, rs197173, and rs926632 in EDN3 were associated with reduced risk of hospitalized bacteremia events in ESRD patients.
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http://dx.doi.org/10.1186/s12882-019-1349-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549338PMC
June 2019

Successful Treatment for BK Virus Nephropathy by Leflunomide in a Kidney Transplant Patient: A Case Report.

Transplant Proc 2019 Jun 10;51(5):1472-1474. Epub 2019 May 10.

Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Introduction: The immunosuppressant agents in kidney transplantation (KT) may lead to various complications such as opportunistic infections and malignancies. BK virus associated nephropathy is a significant complication following KT, and it can result in graft failure. BK virus causes tubulointerstitial nephritis, ureter stenosis, and even graft failure in KT recipients with impaired immune system. We described a 63-year-old woman, who was a hepatitis C carrier and on dialysis for 22 years before KT, who received cadaveric-donor KT 2 years previously. She reported decreasing urine output and general weakness. The serum creatinine level was slightly increased from 2.94 to 4.38 mg/dL.

Methods: Immunosuppressant medications including prednisolone, everolimus, cyclosporin, and mycophenolate sodium were continued as maintenance therapy post KT. Kidney biopsy was performed due to deterioration of graft function.

Results: The kidney biopsy showed consistent results with early-stage polyomavirus nephropathy, characterized by focal viral cytopathic changes with positive immunohistochemical signals and mesangial proliferative glomerulonephritis, immune-complex-mediated (Fig 1 and Fig 2). Negative C4d staining at peritubular capillary was reported. The dosage of mycophenolate sodium was tapered from 720 to 360 mg daily and that of everolimus increased from 0.5 to 1.0 mg daily due to BK viral infection with BK nephropathy. The serum creatinine level was 2.75 mg/dL after treatment.

Conclusion: Early detection of BK nephropathy and decreasing immunosuppressant agents are the mainstay of treatment. Substituting leflunomide for mycophenolate sodium and increasing dosage of everolimus has been proposed to solve BK nephropathy. We presented that the use of leflunomide in such situation is in a timely manner.
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http://dx.doi.org/10.1016/j.transproceed.2019.01.146DOI Listing
June 2019

The association between plasma selenium and chronic kidney disease related to lead, cadmium and arsenic exposure in a Taiwanese population.

J Hazard Mater 2019 08 29;375:224-232. Epub 2019 Apr 29.

Department of Family Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

This study aimed to determine the interaction of red blood cell cadmium and lead, total urinary arsenic, and plasma selenium in chronic kidney disease (CKD). We recruited 220 CKD patients as well as 438 gender- and age-matched controls, and we defined CKD as <60 mL/min/1.73 m estimated glomerular filtration rate (eGFR) for three or more consecutive months. Plasma selenium and red blood cell cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined via HPLC-HG-AAS and were summed to determine the total urinary arsenic concentration. Plasma selenium was positively correlated to eGFR, and subjects with high plasma selenium levels (>243.90 μg/L) had a significantly lower odds ratio (OR) and 95% confidence interval (CI) (0.23, 0.13-0.42) for CKD compared to those with low plasma selenium levels (≤ 196.70 μg/L). High plasma selenium and low red blood cell cadmium or lead concentrations interacted to decrease the OR and 95% CI for CKD (0.12, 0.06-0.26; 0.09, 0.04-0.19). High plasma selenium and low red blood cell lead levels also interacted to increase the eGFR (20.70, 15.56-26.01 mL/min/1.73 m). This study is the first to suggest that selenium modifies the eGFR and OR in CKD induced by environmental toxicants.
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http://dx.doi.org/10.1016/j.jhazmat.2019.04.082DOI Listing
August 2019

Progressive multifocal leukoencephalopathy in a renal transplant patient.

J Neurovirol 2019 08 8;25(4):612-615. Epub 2019 May 8.

Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, No.291, Zhongzheng Rd., Zhonghe District, New Taipei City, 23561, Taiwan.

End-stage renal disease (ESRD) has a major impact on health and affects more than 600,000 people in the USA. The current mainstay treatments include dialysis and kidney transplantation (KT), and patients who have received KT have a higher quality of life and a lower mortality risk than those on chronic dialysis. Therefore, KT is considered the more preferred treatment modality for patients with ESRD. However, even though KT results in a higher long-term survival rate, the use of immunosuppressants is associated with various complications, including opportunistic infections and malignancies, which may lead to a higher risk of death in the first year after transplantation. Progressive multifocal leukoencephalopathy (PML) is a rare complication following KT, with an incidence of 0.027% in KT recipients. We present a case of PML following immunosuppressant therapy in a patient who received KT.
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http://dx.doi.org/10.1007/s13365-019-00749-8DOI Listing
August 2019

A systematic review and meta-analysis of the comparison of performance among step-tip, split-tip, and symmetrical-tip hemodialysis catheters.

J Vasc Surg 2019 04;69(4):1282-1292

Center for Evidence-Based Health Care, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Department of Medical Research, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Division of Cardiovascular Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of General Surgery, Department of Surgery, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Cochrane Taiwan, Taipei Medical University, Taipei, Taiwan; Division of General Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Objective: Patients with end-stage renal disease need vascular access to ensure sufficient blood flow during hemodialysis (HD). Patients who are poor candidates for arteriovenous access creation require long-term catheter placement. Problems such as dialysate recirculation, thrombosis, catheter-related infections, and malfunction can occur with HD catheters. Different tip designs (step, split, and symmetrical) have been developed to ameliorate the catheter-related problems. The aim of the study was to compare the efficacy and safety of split-tip, step-tip, and symmetrical-tip HD catheters.

Methods: The PubMed, Embase, Cochrane Library, and Scopus databases and the ClinicalTrials.gov registry were searched for studies published before November 2017. Studies comparing the clinical and rheologic outcomes of step-, split-, or symmetrical-tip catheters in patients undergoing HD were included in this meta-analysis. We conducted meta-analyses using random-effects models. The primary outcomes were catheter survival time and incidence of functioning catheters. The secondary outcomes were delivered blood flow rate, blood recirculation rate, and incidence of catheter-related complications.

Results: Seven randomized controlled trials and one retrospective study with a total of 988 patients were included. No significant differences were observed in the delivered blood flow rate (weighted mean difference, -5.37 mL/min; 95% confidence interval [CI], -23.75 to 13.02), incidence of catheter-related infections (risk ratio [RR], 1.18; 95% CI, 0.63-2.22), or incidence of catheter-related thrombosis (RR, 1.29; 95% CI, 0.64-2.59) between step-tip catheters and advanced (both split-tip and symmetrical-tip) catheters. Moreover, a meta-analysis of the incidence of functioning catheters at 1 month, 6 months, and 12 months revealed that the outcome of step-tip catheter use was better than that of split-tip catheter use, but with a significant difference only at 6 months (RR, 1.22; 95% CI, 1.02-1.46).

Conclusions: None of the catheter types exhibited unique features that can enhance their suitability for application. Hence, catheters can be selected by also considering different factors, including costs, ease of procedures, expertise of the clinician, and education and preference of the patient.
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http://dx.doi.org/10.1016/j.jvs.2018.09.029DOI Listing
April 2019