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Background: Patients with diabetes kidney disease (DKD) are at risk of developing frailty, leading to functional impairment and poor outcomes. Medications are potential modifiers of such risk. Ketoanalogues have been shown to delay dialysis initiation in DKD patients. We investigated whether ketoanalogues use influenced the risk of worsening frailty in this population. Methods: From 840,000 patients with diabetes, we identified those with DKD but without full-fledged frailty, and divided them into those with and without receiving ketoanalogue, followed by propensity score matching in 1:4 ratio. Worsening frailty was defined as ≥1 positive FRAIL item increase compared to baseline status (0, 1, or 2 items) during follow-up. We used Cox proportional hazard regression to estimate the probability of worsening frailty, adjusting for demographics, comorbidities, glycemic control, renal function, treatments and medications. Results: Totally 183 and 732 ketoanalogue users and matched non-users were identified, respectively. The mean age of included patients was 57.4 years, with 91.3 % having non-dialysis stage 5 chronic kidney disease. Approximately two-thirds had pre-frailty (1 o2 items). After 3.72 years, 16.6 % patients had worsening frailty. Multivariate analyses, adjusting for confounders disclosed that ketoanalogue users (≥14 days) had a significantly lower risk of worsening frailty than non-users (hazard ratio (HR) 0.52, 95 % confidence interval (CI) 0.32–0.87). Sensitivity analysis including those received ketoanalogue ≥28 days showed even greater benefits (HR 0.45, 95 % CI 0.26–0.78). Conclusions: Patients with DKD receiving ketoanalogues were less likely to have worsening frailty over time than non-users. Our findings uncover a new potential strategy of ameliorating frailty progression in this population carrying a high risk of accelerated aging.

Abstract Background The activation of the unfolded protein response (UPR) is closely linked to the pathogenesis of renal injuries. However, the role of XBP1, a crucial regulator of adaptive UPR, remains unclear during the transition from acute kidney injury (AKI) to chronic kidney disease (CKD). Methods We characterized XBP1 expressions in different mouse models of kidney injuries, including unilateral ischemia–reperfusion injury (UIRI), unilateral ureteral obstruction, and adenine-induced CKD, followed by generating proximal tubular XBP1 conditional knockout (XBP1cKO) mice for examining the influences of XBP1. Human proximal tubular epithelial cells (HK-2) were silenced of XBP1 to conduct proteomic analysis and investigate the underlying mechanism. Results We showed a tripartite activation of UPR in injured kidneys. XBP1 expressions were attenuated after AKI and inversely correlated with the severity of post-AKI renal fibrosis. XBP1cKO mice exhibited more severe renal fibrosis in the UIRI model than wide-type littermates. Silencing XBP1 induced HK-2 cell cycle arrest in G2M phase, inhibited cell proliferation, and promoted TGF-β1 secretion. Proteomic analysis identified TNF receptor associated protein 1 (Trap1) as the potential downstream target transcriptionally regulated by XBP1s. Trap1 overexpression can alleviate silencing XBP1 induced profibrotic factor expressions and cell cycle arrest. Conclusion The loss of XBP1 in kidney injury was profibrotic, and the process was mediated by autocrine and paracrine regulations in combination. The present study identified the XBP1-Trap1 axis as an instrumental mechanism responsible for post-AKI fibrosis, which is a novel regulatory pathway.

Abstract Transforming growth factor beta (TGFβ) signalling regulates extracellular matrix accumulation known to be essential for the pathogenesis of renal fibrosis; latent transforming growth factor beta binding protein 4 (LTBP4) is an important regulator of TGFβ activity. To date, the regulation of LTBP4 in renal fibrosis remains unknown. Herein, we report that LTBP4 is upregulated in patients with chronic kidney disease and fibrotic mice kidneys created by unilateral ureteral obstruction (UUO). Mice lacking the short LTBP4 isoform (Ltbp4S −/− ) exhibited aggravated tubular interstitial fibrosis (TIF) after UUO, indicating that LTBP4 potentially protects against TIF. Transcriptomic analysis of human proximal tubule cells overexpressing LTBP4 revealed that LTBP4 influences angiogenic pathways; moreover, these cells preserved better mitochondrial respiratory functions and expressed higher vascular endothelial growth factor A (VEGFA) compared to wild-type cells under hypoxia. Results of the tube formation assay revealed that additional LTBP4 in human umbilical vein endothelial cell supernatant stimulates angiogenesis with upregulated vascular endothelial growth factor receptors (VEGFRs). In vivo, aberrant angiogenesis, abnormal mitochondrial morphology and enhanced oxidative stress were observed in Ltbp4S −/− mice after UUO. These results reveal novel molecular functions of LTBP4 stimulating angiogenesis and potentially impacting mitochondrial structure and function. Collectively, our findings indicate that LTBP4 protects against disease progression and may be of therapeutic use in renal fibrosis.

Abstract Background Patients with diabetic mellitus (DM) and chronic kidney disease (CKD) are at an increased risk of urinary tract infection (UTI) due to their altered immunological integrity. These patients are similarly prone to developing frailty, a state of cumulative health deficits involving multiple domains and leading to adverse outcomes. Whether frailty predisposes affected individuals to UTI among patients with DM and CKD remains unclear. Methods A population-based cohort of patients with DM and CKD (n = 79,887) were assembled from the Longitudinal Cohort of Diabetes Patients, with their baseline frailty status measured by a modified FRAIL scale. We analyzed their risk of developing UTI depending on their severity of frailty, after accounting demographic profiles, lifestyle factors, comorbidities, concurrent medications, and major interventions. A secondary analysis focused on the risk of urosepsis related to frailty. Results Among all participants, 36.1 %, 50.3 %, 12.8 %, and 0.8 % did not have or had 1, 2, and ≥ 3 FRAIL items, respectively, at baseline. After 3.51 years, 11,175 UTI events occurred. Kaplan-Meier analysis showed that participants with DM, CKD and an increasing number of FRAIL items had successively higher incidence of UTI than those without any FRAIL items (log rank p

BackgroundDepression confers substantial disease burden globally, especially among those with chronic kidney disease (CKD). The presence of depression significantly impairs one's quality of life. Risk factors for depression in patients with CKD remain under-appreciated, and whether frailty, a geriatric phenotype, constitutes a risk factor for depression in this population is unknown.MethodsWe prospectively enrolled patients with end-stage renal disease (ESRD) undergoing hemodialysis for >3 months from National Taiwan University Hospital Yunlin Branch between 2019 and 2021. Clinical, physical, functional, and performance parameters were recorded, followed by frailty/sarcopenia assessment. Depression was screened for using the Geriatric Depression Scale. We analyzed the independent relationship between frailty and depression in these patients, using multiple regression analyses.ResultsTotally 151 patients with ESRD were enrolled (mean 61.1 years, 66.9% male), among whom 16.6% had screening-identified depression. ESRD participants with depression did not differ from those without regarding most parameters except serum creatinine, functional indices, and sarcopenia/frailty status. We found that having greater frail severities was independently associated with a higher probability of depression; having FRAIL- (odds ratio [OR] 5.418) and SOF-based (OR 2.858) frailty independently correlated with a higher depression probability. A linear relation exists between a greater frail severity and the probability of depression. Using a more relaxed criterion for detecting depression, higher SOF scores remained significantly associated with an increased depression risk.ConclusionsIn patients with CKD, frailty independently correlated with a higher probability of having depression. Strategies aiming to attenuate frailty may be able to benefit those with depression simultaneously in this population.

Dialysis prevents death from uremia in patients with end-stage renal disease (ESRD). Nevertheless, during hemodialysis, circulating levels of di-(2-ethylhexyl) phthalate (DEHP) are increased due to phthalates leaching from medical tubes. Statins are an effective therapy for reducing the risks associated with cardiovascular diseases in patients with chronic kidney disease; however, the mechanism by which statins fail to reduce cardiovascular events in hemodialysis ESRD patients remains unclear. In this study, we investigated whether DEHP and its metabolites interfere with the lipid-lowering effect of statins in hepatocytes. In Huh7 cells, treatment with DEHP and its metabolites abolished the simvastatin-conferred lipid-lowering effect. Mechanistically, DEHP down-regulated the expression of low-density lipoprotein receptor (LDLR) and led to a decrease in LDL binding, which was mediated by the activation of the PPARγ-PCSK9 and LXRα-IDOL signaling pathways. Additionally, the NOX-ROS-TRPA1 pathway is involved in the DEHP-mediated inhibition of LDLR expression and LDL binding activity. Blockage of this pathway abrogated the DEHP-mediated inhibition in the LDLR expression and LDL binding of simvastatin. Collectively, DEHP induces the activation of the NOX-ROS-TRPA1 pathway, which in turn activates PPARγ-PCSK9- and LXRα-IDOL-dependent signaling, and, ultimately, diminishes the statin-mediated lipid-lowering effect in hepatocytes.

Background: Patients with diabetic kidney disease (DKD) are at an increased risk of frailty. The exposure to muscle relaxants frequently leads to adverse effects despite their modest therapeutic efficacy, but whether muscle relaxants predispose users to frailty remains unclear. Methods: Patients with DKD from a population-based cohort, the Longitudinal Cohort of Diabetes Patients, were identified between 2004 and 2011 ( N = 840,000). Muscle relaxant users were propensity score-matched to never-users in a 1:1 ratio based on demographic features, comorbidities, outcome-relevant medications, and prior major interventions. Incident frailty, the study endpoint, was measured according to a modified FRAIL scale. We used Kaplan–Meier analyses and Cox proportional hazard regression to analyze the association between cumulative muscle relaxant use (⩾ 28 days) and the risk of incident frailty. Results: Totally, 11,637 users and matched never-users were enrolled, without significant differences regarding baseline clinical features. Cox proportional hazard regression showed that patients with DKD and received muscle relaxants had a significantly higher risk of incident frailty than never-users [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.04–1.53]. This increase in frailty risk paralleled that in cumulative muscle relaxant dosages (quartile 1 versus 2 versus 3 versus 4, HR 0.91 versus 1.22 versus 1.38 versus 1.45, p = 0.0013 for trend) and in exposure durations (quartile 1 versus 2 versus 3 versus 4, HR 1.12 versus 1.33 versus 1.23 versus 1.34, p = 0.0145 for trend) of muscle relaxants. Conclusion: We found that cumulative muscle relaxant exposure might increase frailty risk. It is prudent to limit muscle relaxant prescription in patients with DKD. Plain language summary Does cumulative muscle relaxant exposure increase the risk of incident frailty among patients with diabetic kidney disease? Background: Frailty denotes a degenerative feature that adversely influences one’s survival and daily function. Patients with diabetes and chronic kidney disease are at a higher risk of developing frailty, but whether concurrent medications, especially muscle relaxants, aggravate this risk remains undefined. Methods: In this population-based study including 11,637 muscle relaxant users and matched never-users with diabetic kidney disease, we used a renowned frailty-assessing tool, FRAIL scale, to assess frailty severity and examined the incidence of frailty brought by muscle relaxant exposure. Results: We found that users exhibited a 26% higher risk of developing incident frailty compared with never-users, and the probability increased further if users were prescribed higher doses or longer durations of muscle relaxants. Conclusion: We concluded that in those with diabetic kidney disease, cumulative muscle relaxant use was associated with a higher risk of incident frailty, suggesting that moderation of muscle relaxant use in this population can be of potential importance.

The safety of ultraviolet B (UVB) phototherapy with respect to cutaneous carcinogenesis has not been established for patients with chronic kidney disease. To investigate this issue, a nationwide cohort study of 10,805 patients with advanced chronic kidney disease was conducted using data from the National Health Insurance of Taiwan, the Taiwan Cancer Registry, and the national death registry. After a median follow-up of 75 months, 16 of 2,161 patients in the UVB group and 63 of 8,644 patients in the non-UVB group developed skin cancers. Compared with the non-UVB group, patients in the UVB group did not show an increased risk of skin cancer (hazard ratio 1.066; 95% confidence interval 0.584–1.944), non-melanoma skin cancer (hazard ratio 1.067; 95% confidence interval 0.571–1.996), or cutaneous melanoma (hazard ratio 1.009; 95% confidence interval 0.115–8.879). In addition, patients who received more UVB phototherapy did not show an increased risk of skin cancer. UVB phototherapy appears to be a safe treatment for uraemic pruritus in patients with chronic kidney disease.

Background: Vascular calcification (VC) is a subclinical manifestation of vascular disease burden among older adults, conferring an elevated mortality risk. Biomarkers capable of detecting and risk-stratifying VC associated with advanced age remains unavailable, impeding our effort to provide optimal care to geriatric patients.Objectives: In this study, we aimed to investigate whether circulating miR-125b served as a potential indicator for VC in relatively healthy older adults.Methods: Community-dwelling older adults (age ≥65) were prospectively recruited during 2017, followed by clinical features documentation and VC rating based on aortic arch calcification (AAC) and abdominal aortic calcification (AbAC). Multiple logistic regression was done to evaluate the relationship between circulating miR-125b levels, VC presence and severity, followed by selecting the optimal cutoff point for VC diagnosis.Results: A total of 343 relatively healthy older adults (median age, 73.8 years; 40% male; 59.8% having AAC) were enrolled, with a median circulating miR-125b level of 0.012 (interquartile range, 0.003–0.037). Those with more severe AAC had progressively decreasing miR-125b levels (p

Background Vascular calcification (VC) is associated with high morbidity and mortality among older adults, a population that exhibits a higher tendency for developing frailty at the same time. Whether VC serves as a risk factor for the development of frailty in this population remains unclear. Methods and Results We analyzed a prospectively assembled cohort of community‐dwelling older adults between 2014 and 2017 (n=1783). Frailty and prefrailty were determined on the basis of the Study of Osteoporotic Fractures criteria, and VC was measured using semiquantitative aortic arch calcification (AAC) and abdominal aortic calcification scoring. We conducted multiple logistic regression with prefrailty or frailty as the dependent variable, incorporating sociodemographic profiles, comorbidities, medications, laboratory data, AAC status/severity, and other geriatric phenotypes. Among all participants, 327 (18.3%) exhibited either prefrailty (15.3%) or frailty (3.1%), and 648 (36.3%) exhibited AAC. After adjusting for multiple confounders, we found that AAC incidence was associated with a substantially higher probability of prefrailty or frailty (odds ratio [OR], 11.9; 95% CI, 7.9–15.4), with a dose‐responsive relationship (OR for older adults with AAC categories 1, 2, and 3 was 9.3, 13.6, and 52.5, respectively). Similar association was observed for older adults with abdominal aortic calcification (OR, 5.0; 95% CI, 1.3–19.5), and might be replicable in another cohort of patients with end‐stage renal disease. Conclusions Severity of VC exhibited a linear positive relationship with frailty in older adults. Our findings suggest that a prompt diagnosis and potential management of VC may assist in risk mitigation for patients with frailty.

Background/Aims: Awareness of chronic kidney disease (CKD) has been low among affected patients, particularly the older ones. However, whether such awareness is synonymous with the presence of laboratory-diagnosed CKD among older adults is currently unclear. Methods: We enrolled community-dwelling old adults (≥ 65 years) who received health examinations between 2013 and 2016 from a regional metropolitan hospital. Clinical information and geriatric syndromes including depression, cognitive impairment, fall, quality of life, and visual disturbance were evaluated during the medical interview. We compared the differences in clinical features between those with and without self-reported or estimated glomerular filtration rate (eGFR)-based CKD and investigated their influences and interactions on the risk of CKD complications and geriatric syndromes. Results: Among the 2932 enrolled older adults (mean 73.4 ± 7 years), 93 (3%) reported that they had CKD by history, while 306 (10%) had an eGFR < 60 mL/min/1.73m2 persisted for over 3 months. The prevalence of hyperlipidemia, body mass index, waist circumference, leukocyte count, and the incidence of fall differed only between those with and without eGFR-based CKD, but not between those with and without self-reported CKD. A synergistic effect was found between self-reported and eGFR-based CKD regarding the CKD complication severity, including malnutrition (albumin), anemia (hemoglobin), dyslipidemia (serum cholesterol), and geriatric syndromes (cognitive and quality of life impairment). Multivariate regression analyses showed that self-reported CKD exhibited better predictive efficacy for lower serum albumin and hemoglobin than eGFR-based CKD, while the latter outperformed the former for predicting lower serum cholesterol and a higher risk of cognitive impairment. Conclusion: Among older adults, self-reported CKD may not be a surrogate for laboratory-diagnosed CKD and has an independent effect on CKD-related complications.

Abstract Peritoneal adhesions develop after abdominal surgery, trauma or intraperitoneal infections, and have important consequences. The deposition of peritoneal fibrin is a common pathophysiological pathway for the formation of adhesions. Here, we aimed to examine the effects of fibrin-induced cytokine production on peritoneal mesothelial cells (PMCs), and to block the effects of fibrin using an integrin-linked kinase (ILK) inhibitor, QLT-0267. PMCs were cultured from the enzymatic disaggregation of rat omentum. After the PMCs were covered with fibrin, the expression of IL-1β, IL-6, TNFα and VEGF-A increased. This increase in cytokine production was attenuated by QLT-0267, which acted via the inhibition of both the ILK and focal adhesion kinase (FAK) pathways, and subsequently via the GSK-3β pathway. We found that QLT-0267 decreased both the severity of peritoneal adhesion and the serum levels of IL-6 in our post-surgical adhesion mouse model. In conclusion, our study provides novel evidence that fibrin-induced cytokine production may involve in the mechanism of peritoneal adhesion formation. Furthermore, the use of the small molecule inhibitor QLT-0267 is a new strategy in preventing peritoneal adhesion in patients undergoing abdominal surgery.

Abstract Background Sarcopenia is the age‐related degeneration characterized with the decline of skeletal muscle mass, strength, and function. The imbalance of protein synthesis and degradation which jeopardizes immune, hormone regulation, and muscle‐motor neuron connection is the main cause of sarcopenia. There is limited knowledge regarding molecular mechanism of sarcopenia. As the endoplasmic reticulum is the control centre of the protein syntheses and degradation, we hypothesized that endoplasmic reticulum stress and unfolded protein response (UPR) play an important in the development of sarcopenia. Understanding the sarcopenia molecular mechanisms may benefit the therapeutic diagnosis and treatment in the future. Methods Mouse myoblast C2C12 cells are exposed to designated time and concentration of indoxyl sulfate (IS), a uremic toxin of chronic kidney disease. The proliferation, differentiation, and the expression of atrogin 1 are examined. The protein and mRNA expression of IS treated‐C2C12 cells are inspected to distinguish the role of ER stress and oxidative stress underlying the sarcopenia. Results Indoxyl sulfate inhibits myoblast differentiation. We demonstrate that as the number of multi‐nuclei myotube decreased, the differentiation markers including myoD, myoG, and myosin heavy chain are also suppressed. Indoxyl sulfate inhibits myoblast proliferation and induces the myotubular atrophy marker atrogin‐1 protein expression. Indoxyl sulfate stimulates eIF2α phosphorylation and XBP1 mRNA splicing in UPR. Interestingly, the oxidative stress is related to eIF2α phosphorylation but not XBP1 mRNA splicing. The eIF2α phosphorylation triggered by IS reduces myoD, myoG, and myosin heavy chain protein expression, which represents the anti‐myogenic modulation on the early differentiation event. The XBP1 mRNA splicing induced by IS, however, is considered the adaptive response to restore the myogenic differentiation. Conclusions Our studies indicated that the ER stress and UPR modulation are critical in the chronic kidney disease uremic toxin‐accumulated sarcopenia model. We believe that UPR‐related signals showed great potential in clinical application.

Kidney disease is a multifactorial problem, with a growing prevalence and an increasing global burden. With the latest worldwide data suggesting that chronic kidney disease (CKD) is the 12th leading cause of death, it is no surprise that CKD remains a public health problem that requires urgent attention. Multiple factors contribute to kidney disease, each with its own pathophysiology and pathogenesis. Furthermore, microRNAs (miRNAs) have been linked to several types of kidney diseases. As dysregulation of miRNAs is often seen in some diseases, there is potential in the exploitation of this for therapeutic applications. In addition, uptake of interference RNA has been shown to be rapid in kidneys making them a good candidate for RNA therapy. The latest advancements in RNA therapy and lipid-based nanocarriers have enhanced the effectiveness and efficiency of RNA-related drugs, thereby making RNA therapy a viable treatment option for renal disease. This is especially useful for renal diseases, for which a suitable treatment is not yet available. Moreover, the high adaptability of RNA therapy combined with the low risk of lipid-based nanocarriers make for an attractive treatment choice. Currently, there are only a small number of RNA-based drugs related to renal parenchymal disease, most of which are in different stages of clinical trials. We propose the use of miRNAs or short interfering RNAs coupled with a lipid-based nanocarrier as a delivery vehicle for managing renal disease.

Abstract Background Frailty is prevalent among patients with end-stage renal disease (ESRD) and is associated with an increased risk of cognitive impairment. However, apart from its influence on cognition, it is currently unknown whether frailty affects subtler cerebral function in patients with ESRD. Methods Patients with ESRD were prospectively enrolled, with clinical features and laboratory data recorded. The severity of frailty among these patients with ESRD was ascertained using the previously validated simple FRAIL scale, and was categorized as none-to-mild and moderate-to-severe frailty. All participants underwent quantitative electroencephalography (EEG), with band powers documented following the generation of the delta to alpha ratio (DAR) and delta/theta to alpha/beta ratio (DTABR). EEG results were then compared between groups of different levels of frailty. Results In this cohort, (mean age: 68.9 ± 10.4 years, 37% male, 3.4 ± 3 years of dialysis), 20, 60, 40, 17, and 6% patients exhibited positivity in the fatigue, resistance, ambulation, illness, and loss-of-body-weight domains, respectively, with 45.7% being none to mildly frail and 54.3% being moderately to severely frail. Those with mild frailty had a significantly higher delta power compared to those with more severe frailty, involving all topographic sites. Patients with ESRD and severe frailty had significantly lower global, left frontal, left temporo-occipital, and right temporo-occipital DAR and DTABR, except in the right frontal area, and tended to have central accentuation of alpha, beta, and theta power, and more homogeneous DTABR and DAR distribution compared to the findings in those with mild frailty. Conclusions Frailty in patients with ESRD can have subtler neurophysiological influences, presenting as altered EEG findings, which warrant our attention.

IntroductionPatients with autosomal dominant polycystic kidney disease (ADPKD) reach end-stage renal disease in their fifth decade on average. For effective treatment and early intervention, identifying subgroups with rapid disease progression is important in ADPKD. However, there are no epidemiological data on the clinical manifestations and disease progression of patients with ADPKD from the Asia-Pacific region.Methods and analysisThe RAPID-ADPKD (Retrospective epidemiological study of Asia-Pacific patients with rapId Disease progression of Autosomal Dominant Polycystic Kidney Disease) study is a multinational, retrospective, observational cohort study of patients with ADPKD in the Asia-Pacific region (Australia, China, Hong Kong, South Korea, Taipei and Turkey). This study was designed to identify the clinical characteristics of patients with ADPKD with rapid disease progression. Adult patients with ADPKD diagnosed according to the unified ultrasound criteria and with an estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2 at baseline will be included. The cohort will include patients with ≥2 records of eGFR and at least 24 months of follow-up data. Demographic information, clinical characteristics, comorbidities, medications, eGFR, radiological findings that allow calculation of height-adjusted total kidney volume, ADPKD-related complications and the Predicting Renal Outcomes in autosomal dominant Polycystic Kidney Disease (PRO-PKD) score will be collected. Rapid progression will be defined based on the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) guideline. All other patients without any of these criteria will be classified to be of slow progression. Clinical characteristics will be compared between patients with rapid progression and those with slow progression. The incidence of complications and the effects of race and water intake on renal progression will also be analysed. The planned sample size of the cohort is 1000 patients, and data from 600 patients have been collected as of 30 May 2019.Ethics and disseminationThis study was approved or is in the process of approval by the institutional review boards at each participating centre. The results will be presented in conferences and published in a journal, presenting data on the clinical characteristics, risk factors for disease progression and patterns of complications of ADPKD in Asian populations.

Background Cardiovascular disease is the leading cause of morbidity and mortality in patients with end‐stage renal disease. Heart rhythm complexity analysis has been shown to be useful in predicting outcomes in various diseases; however, data on patients with end‐stage renal disease are limited. In this study, we analyzed the association between heart rhythm complexity and long‐term cardiovascular outcomes in patients with end‐stage renal disease receiving peritoneal dialysis. Methods and Results We prospectively enrolled 133 patients receiving peritoneal dialysis and analyzed linear heart rate variability and heart rhythm complexity variables including detrended fluctuation analysis (DFA) and multiscale entropy. The primary outcome was cardiovascular mortality, and the secondary outcome was the occurrence of major adverse cardiovascular events. After a median of 6.37 years of follow‐up, 21 patients (22%) died from cardiovascular causes. These patients had a significantly lower low‐frequency band of heart rate variability, low/high‐frequency band ratio, total power band of heart rate variability, heart rate turbulence slope, deceleration capacity, short‐term DFA (DFAα1); and multiscale entropy slopes 1 to 5, scale 5, area 1 to 5, and area 6 to 20 compared with the patients who did not die from cardiovascular causes. Time‐dependent receiver operating characteristic curve analysis showed that DFAα1 had the greatest discriminatory power for cardiovascular mortality (area under the curve: 0.763) and major adverse cardiovascular events (area under the curve: 0.730). The best cutoff value for DFAα1 was 0.98 to predict both cardiovascular mortality and major adverse cardiovascular events. Multivariate Cox regression analysis showed that DFAα1 (hazard ratio: 0.076; 95% CI, 0.016–0.366; P=0.001) and area 1 to 5 (hazard ratio: 0.645; 95% CI, 0.447–0.930; P=0.019) were significantly associated with cardiovascular mortality. Conclusions Heart rhythm complexity appears to be a promising noninvasive tool to predict long‐term cardiovascular outcomes in patients receiving peritoneal dialysis.

Frailty exhibits diverse influences on health-related outcomes and represents a surrogate of increased susceptibility to harmful injuries. Patients with chronic kidney disease (CKD) are at a higher risk of accelerated biologic aging, and, in this population, the concept of frailty emerges as an instrumental measurement of physiologic reserves. However, a comprehensive description of known independent contributors to, and risk associates of, frailty in these patients remain unavailable. In the present review, original studies up to 28 February 2019 that assessed frailty in patients with all stages of CKD were retrieved and reviewed, with results extracted and summarized. By pooling 62 original investigations, 58.1% and 49.1% used cohort and cross-sectional designs, respectively. Dialysis-dependent end-stage renal disease patients ( n = 39; 62.9%) were the most commonly examined population, followed by those with nondialysis CKD ( n = 12; 19.4%) and those receiving renal transplantation ( n = 11; 17.7%). Contributors to frailty in CKD patients included sociodemographic factors, smoking, CKD severity, organ-specific comorbidities, depression, hypoalbuminemia, and low testosterone levels. Conversely, the development of frailty was potentially associated with the emergence of cardiometabolic, musculoskeletal, and cerebral complications; mental distress; and a higher risk of subsequent functional and quality-of-life impairment. Moreover, frailty in CKD patients increased healthcare utilization and consistently elevated mortality among affected ones. Based on the multitude of contributors to frailty and its diverse health influences, a multifaceted approach to manage CKD patients with frailty is needed, and its potential influences on outcomes besides mortality need to be considered.

Background: End-stage renal disease is an independent risk factor for postoperative mortality and cardiovascular events, but dialysis vintage and its relationship with perioperative complication is not well studied. We did a population-based study to investigate this issue. Materials and methods: We identified patients who had total knee arthroplasty (TKA) or total hip arthroplasty (THA) surgeries during 1999–2010 from the National Health Insurance Research Database of Taiwan. Patients who had regular dialysis before surgery were recruited in our analysis. The outcome of interest was mortality, morbidities, intensive care unit admission rate, hospitalization duration, readmission rate, and medical costs. We did multivariate regression to adjust for age, sex, and Charlson comorbidity index (CCI) and to analyze the relationship of dialysis vintage and clinical outcomes. Results: A total of 518 patients were enrolled for analysis. A total of 286 patients had TKA surgeries and 232 patients had THA surgeries. Patients who had TKA surgery were older and had more medical comorbidities than patients who had THA. After adjustment for age, sex, and CCI, TKA patients who had dialysis vintage

Patients with chronic kidney disease (CKD) have an increased risk of vascular calcification (VC), including aortic arch calcification (AAC). Few investigated the influence of gustatory function on the probability of having VC. We examined whether gustatory function results modulated the probability of having VC in patients with CKD. We prospectively enrolled adults with CKD (estimated glomerular filtration rate 2), with their AAC rated semi-quantitatively and gustatory function assessed by objective and subjective approaches. Multiple logistic regression was used to analyze the relationship between gustatory function results and AAC. Those with AAC had significantly better objective gustatory function in aggregate scores (p = 0.039) and categories (p = 0.022) and less defective bitter taste (p = 0.045) and scores (p = 0.037) than those without. Multiple regression analyses showed that higher aggregate scores (odds ratio (OR) 1.288, p = 0.032), or better gustatory function, and higher bitter taste scores (OR 2.558, p = 0.019) were each associated with a higher probability of having AAC among CKD patients; such an association was modulated by serum phosphate levels. In conclusion, better gustatory function was independently correlated with having AAC among CKD patients. A follow-up of VC severity may be an underrecognized component of care for CKD patients with a preserved gustatory function.

Background MicroRNA‐125b (miR‐125b) has been shown to regulate vascular calcification (VC), and serum miR‐125b levels are a potential biomarker for estimating the risk of uremic VC status. However, it is unknown whether clinical features, including chronic kidney disease–mineral bone disorder molecules, affect serum miR‐125b levels. Methods and Results Patients receiving chronic dialysis for ≥3 months were recruited from different institutes. Serum miR‐125b and chronic kidney disease–mineral bone disorder effectors, including intact parathyroid hormone, 25‐OH‐D, fibroblast growth factor‐23, osteoprotegerin, and fetuin‐A, were quantified. We used multivariate regression analyses to identify factors associated with low serum miR‐125b levels and an area under receiver operating characteristic curve curve to derive optimal cutoffs for factors exhibiting close associations. Further regression analyses evaluated the influence of miR‐125b on VC risk. Among 223 patients receiving chronic dialysis (mean age, 67.3 years; mean years of dialysis, 5.2), 54 (24.2%) had high serum miR‐125b levels. Osteoprotegerin (P=0.013), fibroblast growth factor‐23 (P=0.006), and fetuin‐A (P=0.036) were linearly associated with serum miR‐125b levels. High osteoprotegerin levels independently correlated with high serum miR‐125 levels. Adding serum miR‐125b levels and serum osteoprotegerin levels (≥400 pg/mL) into models estimating the risk of uremic VC increased the area under receiver operating characteristic curve values (for models without miR‐125b/osteoprotegerin, with miR‐125b, and both: 0.74, 0.79, and 0.81, respectively). Conclusions Serum osteoprotegerin levels ≥400 pg/mL and serum miR‐125b levels synergistically increased the accuracy of estimating VC risk among patients receiving chronic dialysis. Taking miR‐125b and osteoprotegerin levels into consideration when estimating VC risk may be recommended.

Background: Acarbose has been deemed contraindicated in diabetic patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD), but such use is not uncommon. We tested whether this concept hold true in this population with different background hepatic diseases.Methods: All incident diabetic patients (n = 2,036,531) with stage 5 CKD/ESRD were enrolled from Taiwan between 2017 and 2013 and divided into those without chronic liver disease (CLD), with CLD but without cirrhosis, and those with cirrhosis. Among each group, acarbose users, defined as cumulative use >30 days within the preceding year, were propensity-score matched 1:2 to non-users. Our main outcome was the development of liver injury events during follow-up.Results: Acarbose users did not exhibit an increased incidence of liver injury during follow-up compared to non-users (hazard ratio and 95% confidence interval, 1.04 [0.88–1.25], 0.97 [0.61–1.56], and 0.71 [0.33–1.54] among those without CLD, with CLD but without cirrhosis, and those with cirrhosis, respectively), after adjusting for demographic profiles, comorbidities, potentially hepatotoxic medication use, and diabetic severity.Conclusions: The incidence of liver injury did not increase significantly among diabetic acarbose users with severe renal insufficiency than non-users, regardless of the presence or absence of chronic liver disease. Our findings support the renaissance of acarbose as a useful adjunct in diabetic patients with stage 5 and 5D chronic kidney disease.

BACKGROUND:Uremic pruritus is a common and frustrating symptom among patients receiving peritoneal dialysis (PD). This study aimed to examine the prognostic importance of uremic pruritus and to identify the determinants for higher pruritus intensity in PD patients. METHODS:We conducted a prospective cohort study of patients receiving maintenance PD. A visual analogue scale (VAS) score was used to measure the intensity of uremic pruritus. The composite endpoint of PD technique failure or all-cause death was assessed using a multivariable Cox proportional hazards model. The determinants for the VAS score of uremic pruritus was assessed using a multivariable linear regression model. RESULTS:Among the 85 PD patients, 24 (28%) had uremic pruritus. During a median follow-up of 28.0 months, 12 patients experienced technique failure, and 7 died. We found that a higher VAS score of pruritus intensity was an independent risk factor for technique failure or death (hazard ratio, 1.64; 95% confidence interval, 1.18 to 2.28; P = 0.003) after adjusting for a variety of confounding factors. We also found that a weekly total Kt/V of less than 1.88, a longer duration of dialysis, a higher dietary protein intake, and higher blood levels of intact parathyroid hormone and high-sensitivity C-reactive protein were independent determinants of higher VAS scores of pruritus intensity. CONCLUSIONS:Our results show that uremic pruritus is an independent risk factor of technique failure and death in patients receiving PD. We also found that a weekly total Kt/V < 1.88 is associated with higher intensity of uremic pruritus in PD patients.

Background Renal supportive care (RSC) is an important option for elderly individuals reaching end-stage renal disease; however, the frequency of RSC practice is very low among Asian countries. We evaluated the attitude, the knowledge, and the preference for specific topics concerning RSC among participants who worked in different medical professions in Taiwan. Methods A cross-sectional questionnaire-based survey was employed. Healthcare personnel (N = 598) who were involved in caring for end-stage renal disease patients at more than 40 facilities in Taiwan participated in this study. Participants were asked about their motivation for learning about RSC, the topics of RSC they were most and least interested in, their willingness to provide RSC, and to rate their knowledge and perceived importance of different topics. Results The vast majority of respondents (81.9%) were self-motivated about RSC, among whom nephrologists (96.8%) and care facilitators (administrators/volunteers) (45%) exhibited the highest and the least motivation, respectively (p

Background Frailty exhibits a high prevalence in end-stage renal disease (ESRD) patients and is associated with adverse health-related outcomes, including falls and fractures. Available studies do not address whether frailty is associated with temporal changes in BMD. We evaluated this issue by analyzing the follow-up dual energy X-ray absorptiometry (DXA) results in an ESRD cohort. Methods In 2015, we enrolled forty-three ESRD patients, divided into frail, pre-frail, and robust ones based on a validated simple FRAIL scale, all receiving DXA at baseline. After one year of follow-up, survivors received another DXA, and we calculated the absolute and percentage changes in area, bone mineral density (BMD), T-, and Z-scores of lumbar spine and femoral neck (FN) between baseline and follow-up examinations. Results Among all, frail individuals with ESRD had significantly lower average lumbar spine area, lower L4, FN, and total BMD and T-scores, lower FN and total Z-scores than non-frail ones, without differences in gender, body mass index, dialysis duration, and comorbidities. Furthermore, we discovered frail ESRD patients had significantly more prominent decrease in average lumbar spine area, percentage changes in L1 Z-scores and average lumbar spine area, and a trend toward more prominent decrease in L4 area than non-frail ones after one year of follow-up. Conclusions Baseline frailty might be associated with deteriorating bone health, including shrinking L-spine areas and a more rapid decrease in L-spine Z scores, among ESRD patients. This frailty-bone association should be highlighted during our care of frail individuals with ESRD.

Withdrawal from dialysis is ethically appropriate for some patients with multiple comorbidities and a shortened life expectancy. Taiwan has the highest prevalence of dialysis patients in the world, and the National Health Insurance (NHI) program offers renal replacement therapy free of charge. In this review, we discuss its current status and many background issues related to withdrawing dialysis from patients with advanced renal failure in Taiwan. Compared with dialysis therapy, the medical resources for hospice care are relatively sparse. Since the announcement of the Statute for Palliative Care in 2000, there has been a gradual improvement in the laws and health polices supporting dialysis withdrawal. Culture and social customs also have a significant impact on the practice of hospice care. Based on current evidence and in accordance with the local environment, we propose recommendations for the clinical practice of dialysis withdrawal and hospice care. There remains a need to expand upon the community-based hospice care and home care systems to better serve patients. In conclusion, there are cross-cultural differences relating to dialysis withdrawal between Taiwan and Western countries. Our experience and clinical recommendations may be helpful for the countries with NHI systems or for the Eastern countries.

Continuous renal replacement therapy (CRRT) is one of the dialysis modalities for critically ill patients. Despite intensive dialysis care, a high mortality rate is found in these patients. Our objective was to investigate the factors associated with poor outcomes in these patients. We conducted a retrospective cohort study using the National Health Insurance Research Database. Records of critically ill patients who received CRRT between 2007 and 2011 were retrieved, and the patients were categorized into two groups: those with acute kidney injury (AKI) and those with history of end-stage renal disease (ESRD). Our primary and secondary outcomes were in-hospital mortality and long-term survival and non-renal recovery (long-term dialysis dependence), respectively, in the AKI group. We enrolled 15,453 patients, with 13,204 and 2249 in the AKI and ESRD groups, respectively. Overall, 66.5% patients died during hospitalization. In-hospital mortality did not differ significantly between groups (adjusted odds ratio, 0.93; 95% CI, 0.84-1.02). Age, chronic liver disease, and cancer history were identified as independent risk factors for in-hospital mortality in both groups. Hypertension was associated with higher risk of in-hospital mortality in patients with AKI. Age, coronary artery disease, and admission to the medical intensive care unit (MICU) were risk factors for long-term dialysis dependence in patients with AKI. Patients with AKI and ESRD have similarly poor outcomes after CRRT. Older age and presence of chronic liver disease and cancer were associated with higher mortality. Older age, presence of coronary artery disease, and admission to MICU were associated with lower renal recovery rate in patients with AKI.

Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are considered to have similar renoprotective effects; so far there has been no consensus about their priorities. This study aimed to compare ACEIs and ARBs for major renal outcomes and survival in a 15-year cohort of adults with diabetes.This study utilized Taiwan's medical and pharmacy claims data in the Longitudinal Cohort of Diabetes Patients. The primary outcome was long-term dialysis, and secondary outcomes were hospitalization for acute kidney injury, hospitalization for hyperkalemia, all-cause death, cardiovascular death, and non-cardiovascular death. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes comparing ACEIs with ARBs. We conducted subgroup analyses and interaction tests among patients with different age and comorbid diseases.A total of 34,043 patients received ACEIs and 23,772 patients received ARBs. No differences were found for primary or secondary outcomes in the main analyses. ACEIs showed significantly lower hazard than ARBs for long-term dialysis among patients with cardiovascular disease (HR 0.80, 95% CI 0.66-0.97, interaction P = 0.003) or chronic kidney disease (0.81, 0.71-0.93, interaction P = 0.001).Our analyses show similar effects of ACEIs and ARBs in patients with diabetes. However, ACEIs might provide additional renoprotective effects among patients who have cardiovascular disease or chronic kidney disease.

Background. Geriatric syndromes (GS) exhibit high prevalence in patients with end-stage renal disease (ESRD) under chronic dialysis irrespective of age. We sought to determine whether GS influences medication adherence in ESRD patients. Methods. A prospective cohort of chronic dialysis patients was assembled. The presence of GS components, including frailty/prefrailty, polypharmacy, and malnutrition, were ascertained through a validated questionnaire, electronic records and chart abstraction, and laboratory tests. The severity of medication non-adherence was defined using the eight-item Morisky Medication Adherence Scale (MMAS). Multiple logistic regression analysis was performed targeting MMAS results and incorporating relevant clinical features and GS. Results. The prevalence of frailty/pre-frailty, polypharmacy, and hypoalbuminemia/ malnutrition among the enrolled participants was 66.7%, 94%, and 14%, respectively. The average MMAS scores in these dialysis patients were 2 ± 1.7 (range, 0–6), with only 15.7% exhibiting high medication adherence. Multiple regression analyses showed that the absence of frailty/pre-frailty (P = 0.01) were significantly associated with poorer medication adherence, while the presence of polypharmacy (P = 0.02) and lower serum albumin, a potential sign of malnutrition (P = 0.03), were associated with poor adherence in another model. Conclusion. This study is among the very few reports addressing GS and medication adherence, especially in ESRD patients. Interventions targeting frailty, polypharmacy, and malnutrition might potentially improve the medication non-adherence and symptom control in these pill-burdened patients.

Background. Patients with end-stage renal disease (ESRD) have a high symptom burden, among which fatigue is highly prevalent. Many fatigue-assessing instruments exist, but comparisons among instruments in this patient population have yet to be investigated. Methods. ESRD patients under chronic hemodialysis were prospectively enrolled and seven types of fatigue instruments were administered: Brief Fatigue Inventory (BFI), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), Fatigue Severity Scale (FSS), Lee Fatigue Scale (LFS), Fatigue Questionnaire (FQ), Fatigue Symptom Inventory (FSI), and Short-Form 36-Vitality (SF36-V). Using these instruments, we investigated the correlation between fatigue severity and clinical/biochemical parameters, including demographic/comorbidity profile, dialysis-related complications, and frailty severity. We used regression analysis with serum albumin and frailty severity as the dependent variables to investigate the independent correlations. Results. A total of 46 ESRD patients were enrolled (average age of 67 ± 11.6 years), and 50% of them had type 2 diabetes mellitus. Results from the seven tested instruments showed high correlation with each other. We found that the fatigue severity by FACIT-F was significantly associated with age (p = 0.03), serum albumin (p = 0.003) and creatinine (p = 0.02) levels, while SF36-V scores were also significantly associated with age (p = 0.02) and serum creatinine levels (p = 0.04). However, the fatigue severity measured by the FSS, FSI, FQ, BFI, and LFS did not exhibit these associations. Moreover, regression analysis showed that only FACIT-F scores were independently associated with serum albumin levels and frailty severity in ESRD patients. Conclusion. Among the seven fatigue-assessing instruments, only the FACIT-F yielded results that demonstrated significant and independent associations with important outcome-related features in ESRD patients.

Sevelamer hydrochloride is a recently developed phosphate binder, which is a quaternary amine anion exchanger without calcium or aluminum. Sevelamer is effective in controlling hyperphosphatemia without increasing the calcium load in chronic hemodialysis (HD) patients. We investigated whether sevelamer restored bone metabolism in chronic HD patients. Methods: An 8-week, prospective, open-label, randomized study was conducted after a 2-week washout period in chronic hyperphosphatemic HD patients. This study compared the effect of sevelamer on markers of bone turnover with that of calcium acetate, as stratified by baseline serum intact parathyroid hormone (iPTH) level. Results: There was no difference in the changes of serum phosphorus, calcium-phosphorus product and serum iPTH between the sevelamer and the calcium acetate groups. However, more hypercalcemic events (12%) were documented under calcium acetate treatment. In patients with hypoparathyroidism, calcium acetate treatment decreased serum iPTH at the end of the study, while sevelamer did not. Increased serum alkaline phosphatase levels were found among patients receiving sevelamer treatment compared with those who received calcium acetate treatment. In those patients receiving sevelamer, the serum alkaline phosphatase level was also positively correlated to the sevelamer dosage (r = 0.246, p = 0.013). Conclusion: Sevelamer effectively reduces serum phosphorus with a lower incidence of hypercalcemic effects in HD patients. Sevelamer is an effective means of treatment for chronic hyperphosphatemic HD patients, especially those with hypoparathyroidism.

Darbepoetin alfa can be administered less frequently than recombinant human erythropoietin (r-HuEPO) for the treatment of anemia in chronic renal failure (CRF) patients. We aimed to confirm that darbepoetin alfa at a reduced dosing schedule can safely maintain a target hemoglobin level in CRF patients undergoing peritoneal dialysis. Methods: Forty-five PD patients receiving r-HuEPO were randomized in a 1:1 ratio to continue r-HuEPO or to change to darbepoetin alfa (open-label). Patients were maintained within a target range of hemoglobin for 5.5 months by adjusting the dose and then the frequency of darbepoetin alfa and r-HuEPO over the initial 4 months. The evaluation period was the final 1.5 months. A total of 37 patients completed the study. Results: During the evaluation period, the hemoglobin of the darbepoetin alfa group was higher than that in the baseline period (10.46 ± 0.22 g/dL vs. 9.98 ± 0.18 g/dL, p < 0.05). Hemoglobin remained similar in the r-HuEPO group. The average dose in the darbepoetin alfa group was 93.0 μg/month, while the average dose in the r-HuEPO group was 18,339.9 units/month. The dosing frequency was less in the darbepoetin alfa group (3.9 times/month vs. 9.2 times/month). We divided the darbepoetin alfa group into low-dose (< 70 μg/month) and high-dose (≥ 70 μg/month) subgroups. The body weight in the high-dose group was higher than that in the low-dose group (66 ± 11 kg vs. 52 ± 4.4 kg, p < 0.01). Conclusion: Both darbepoetin alfa and r-HuEPO safely maintain hemoglobin levels within the target range in peritoneal dialysis patients.

Patients with severe kidney function impairment often have autonomic dysfunction, which could be evaluated noninvasively by heart rate variability (HRV) analysis. Nonlinear HRV parameters such as detrended fluctuation analysis (DFA) has been demonstrated to be an important outcome predictor in patients with cardiovascular diseases. Whether cardiac autonomic dysfunction measured by DFA is also a useful prognostic factor in patients with end-stage renal disease (ESRD) receiving peritoneal dialysis (PD) remains unclear. The purpose of the present study was designed to test the hypothesis.Patients with ESRD receiving PD were included for the study. Twenty-four hour Holter monitor was obtained from each patient together with other important traditional prognostic makers such as underlying diseases, left ventricular ejection fraction (LVEF) and serum biochemistry profiles. Short-term (DFAα1) and long-term (DFAα2) DFA as well as other linear HRV parameters were calculated.A total of 132 patients (62 men, 72 women) with a mean age of 53.7±12.5 years were recruited from July 2007 to March 2009. During a median follow-up period of around 34 months, eight cardiac and six non-cardiac deaths were observed. Competing risk analysis demonstrated that decreased DFAα1 was a strong prognostic predictor for increased cardiac and total mortality. ROC analysis showed that the AUC of DFAα1 (

Low lean body mass (LBM) is an indicator of malnutrition inflammation syndrome, which is common in hemodialysis (HD) patients. The creatinine index (CI) has been validated as a reliable method to estimate LBM and evaluate the protein-energy status of HD patients. However, the traditional creatinine index formula was complex. We sought to investigate the impact of CI derived from a new simple formula on Chinese HD patient outcomes.In this retrospective cohort study, we enrolled 1269 patients who initiated HD between February 1981 and February 2012 and followed them until the end of February 2013. CI was calculated using the simple creatinine kinetic model (CKM) formula. Multiple linear regression analysis and Cox regression proportional hazard analysis were used to define independent variables and compare survival between groups.The 1269 HD patients were categorized into 3 groups according to the tertiles of calculated CI between men and women. Each group consisted of 423 patients (50.6% men, 49.4% women). Patients in the highest sex-specific tertile of CI had longer overall survival (HR, 0.46; P 0.002). BMI did not significantly associate with survival after adjustment (HR,0.99; P 0.613).CI derived from the simple CKM formula serves as a good parameter than BMI to predict the survival of HD patients. The formula could extend its convenient use in clinical practice for HD patients.

End-stage renal disease (ESRD) patients are at increased risk of sudden cardiac death, the risk of which is presumably related to arrhythmia. Electrocardiographic (ECG) parameters have been found to correlate with arrhythmia and predict cardiovascular outcomes in ESRD patients. Frailty is also a common feature in this population. We investigate whether the severity of dialysis frailty is associated with ECG findings, including PR interval, QRS duration, and QTc interval. Presence and severity of frailty was ascertained using six different self-report questionnaires with proven construct validity. Correlation analysis between frailty severity and ECG was made, and those with significant association entered into multiple regression analysis for confirmation. Among a cohort of chronic hemodialysis patients, we found that frailty severity, assessed by the Edmonton frailty scale, is significantly associated with QRS duration (r = − 0.3, p < 0.05). Dialysis patients with QRS longer than 120 ms had significantly lower severity of frailty than those with QRS less than 120 ms (p = 0.01 for the Edmonton frailty scale and 0.05 for simple FRAIL scale). Regression analysis showed that frailty severity, assessed by the Edmonton frailty scale and simple FRAIL scale, was significantly associated with QRS duration independent of serum electrolyte levels. In conclusion, a significant relationship exists between the severity of frailty and QRS duration in ESRD patients. This might be an under-recognized link between frailty and its adverse cardiovascular impact in these patients.

Despite the abundance of wild mushrooms growing in a variety of habitats in Taiwan, mushroom poisoning is rarely reported. Here, we report two cases of mushroom poisoning, possibly due to Amanita smithiana or a related species. A 54-year-old man and his 52-year-old wife presented with acute anuric renal failure 1 day after ingesting some white mushrooms they had collected when mountain climbing; they made a full recovery following hemodialysis and supportive treatment. Although rare, mushroom poisoning should be considered in the differential diagnoses of acute renal failure.

Acinetobacter species are assuming an increasingly important role in modern medicine, with their persistent presence in health-care settings and antibiotic resistance. However, clinical reports addressing this issue in patients with peritoneal dialysis (PD) peritonitis are rare.All PD peritonitis episodes caused by Acinetobacter that occurred between 1985 and 2012 at a single centre were retrospectively reviewed. Clinical features, microbiological data, and outcomes were analysed, with stratifications based upon temporal periods (before and after 2000).Acinetobacter species were responsible for 26 PD peritonitis episodes (3.5% of all episodes) in 25 patients. A. baumannii was the most common pathogen (54%), followed by A. iwoffii (35%), with the former being predominant after 2000. Significantly more episodes resulted from breaks in exchange sterility after 2000, while those from exit site infections decreased (P = 0.01). The interval between the last and current peritonitis episodes lengthened significantly after 2000 (5 vs. 13.6 months; P = 0.05). All the isolates were susceptible to cefepime, fluoroquinolone, and aminoglycosides, with a low ceftazidime resistance rate (16%). Nearly half of the patients (46%) required hospitalisation for their Acinetobacter PD-associated peritonitis, and 27% required an antibiotic switch. The overall outcome was fair, with no mortality and a 12% technique failure rate, without obvious interval differences.The temporal change in the microbiology and origin of Acinetobacter PD-associated peritonitis in our cohort suggested an important evolutional trend. Appropriate measures, including technique re-education and sterility maintenance, should be taken to decrease the Acinetobacter peritonitis incidence in PD patients.

BACKGROUND: Reduced lean body mass (LBM) is one of the main indicators in malnutrition inflammation syndrome among patients on dialysis. However, the influence of LBM on peritoneal dialysis (PD) patients' outcomes and the factors related to increasing LBM are seldom reported. METHODS: We enrolled 103 incident PD patients between 2002 and 2003, and followed them until December 2011. Clinical characteristics, PD-associated parameters, residual renal function, and serum chemistry profiles of each patient were collected at 1 month and 1 year after initiating PD. LBM was estimated using creatinine index corrected with body weight. Multiple linear regression analysis, Kaplan-Meier survival analysis, and Cox regression proportional hazard analysis were used to define independent variables and compare survival between groups. RESULTS: Using the median LBM value (70% for men and 64% for women), patients were divided into group 1 (n = 52; low LBM) and group 2 (n = 51; high LBM). Group 1 patients had higher rates of peritonitis (1.6 vs. 1.1/100 patient months; p

OBJECTIVE: Patients with symptoms of heart failure and preserved left ventricular (LV) systolic function are commonly encountered in clinical practice especially in peritoneal dialysis (PD) patients. We hypothesized that adiposity might influence LV diastolic function through systemic inflammation in this specific group. METHODS: We designed a cross-sectional study in 173 prevalent PD patients. LV diastolic dysfunction was diagnosed by echocardiography. PD patient without LV diastolic dysfunction served as the control group. Serum inflammatory biomarkers were examined including tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The location and amount of adipose tissue were assessed by computerized tomography (CT) at the level of the fourth lumbar vertebra. RESULTS: Subjects with LV diastolic dysfunction had higher levels of the pro-inflammation cytokines and more visceral and peritoneal fat (all P

BackgroundPeritoneal calcification (PC) is a specific finding in patients undergoing peritoneal dialysis (PD), but its prevalence, risk factors, and impacts in PD patients remain unclear. The present study investigated these issues and provided information useful for the management of PC.MethodsThe study included 183 PD patients. The severity of PC was determined using abdominal computed tomography (CT), and we summed up all scores from slices obtained from the diaphragm to the pelvic floor normalized to body surface area. We analyzed the associations between PC and demographic and clinical characteristics, and between PC and levels of biomarkers, including C-reactive protein (CRP), osteoprotegrin and fetuin-A. The determinants of PC were examined using multiple regression analysis.ResultsPatients were categorized into group 1 (without PC, n = 133) and group 2 (with PC, n = 50). Group 2 patients showed different degrees of PC with a mean of 160±769 mm(2)/m(2). Group 1 patients had higher fetuin-A levels than group 2 patients (861±309 vs. 760±210 µg/mL; p = 0.021). The independent risk factors for the presence of PC included male gender, previous peritonitis, and PD adequacy (KT/V). Further analysis performed in group 2 patients showed that the dosage of vitamin D, serum levels of CRP, and dialysate calcium load were the independent determinants of PC. However, the presence of PC did not affect patients' technique survival, peritonitis incidence, or mortality in the mean follow up period of 28±12 months.ConclusionsThe presence and severity of PC were associated with inflammation, peritoneal KT/V, and mineral metabolism. The impact of PC on the outcomes of PD patients requires further study with a longer follow-up.

Diabetes mellitus (DM) is the most common cause of end-stage renal disease and is an important risk factor for morbidity and mortality after dialysis. However, glycemic control among such patients is difficult to assess. The present study examined glycemic control parameters and observed glucose variation after refilling different kinds of fresh dialysate in peritoneal dialysis (PD) patients.A total of 25 DM PD patients were recruited, and continuous glucose monitoring system (CGMS) was applied to measure interstitial fluid (ISF) glucose levels at 5-min intervals for 3 days. Patients filled out diet and PD fluid exchange diaries. The records measured with CGMS were analyzed and correlated with other glycemic control parameters such as fructosamine, albumin-corrected fructosamine (AlbF), glycosylated hemoglobin (HbA1c), and glycated albumin levels.There were significant correlations between mean ISF glucose and fructosamine (r = 0.45, P

This study aimed to evaluate the effects of soy protein and nutrition education on patients with chronic kidney disease (CKD). Patients who were regularly followed up at the nephrology clinics of National Taiwan University Hospital, aged between 18 to 75 years, daily activities-independent, had normal liver function, and had stage III, IV or V CKD were invited to join this study. The enrolled patients were then divided into two groups by simple randomization. Group 1 patients were asked to eat meat while Group 2 patients eat soy bean as their major sources of protein intake for a period of 6 months. Diet education for CKD was given at the start, the 3rd month, and the end of study. Demographic, clinical as well as laboratory data including serum biochemistry, lipid profile, interleukin-6, serum adiponectin, indirect calorimetry, and body composition were compared between the two groups both at the beginning and at the end of study. There were 26 CKD patients who had finished the study, but only 23 of them had complete laboratory data. There was no statistical difference in the baseline demographic, clinical and laboratory data between Group 1 and Group 2 patients except for serum albumin level (4.7±0.2 versus 4.4±0.2 g/dL, P=0.0013) (Table 1). There was neither any statistical difference in the baseline indirect calorimetry and body composition data between the two groups except for body fat percentage (23.1±6.2 versus 28.9±6.5%, P=0.0380). After 6 months of intervention, Group 2 patients were noted to have significantly higher adiponectin level than Group 1 patients (−3776.0±9118.3 versus 9073.5±9748.1 pg/mL, P=0.0049) (Table 2). There was no statistical difference in indirect calorimetry change or body composition change between the 2 groups though Group 2 patients were on average lighter at the end of study (P=0.0532).

Nutrition is one of the important issues and edema will overestimate the real body weight among dialysis patients. Lean body mass might reflect the real nutrition status. Creatinine is the product of muscle metabolism, creatinine generation can reflect the lean body mass (LBM). In peritoneal dialysis (PD) patients, creatinine generation could be evaluated by routine clearance measurement. This study will investigate the relationship among LBM, patient survival and PD technique therapy. Between 2002 and 2003, a total 115 patients who underwent PD for more than 3 months were enrolled in this study. Follow up ended in Dec. 2011. These patients were categorized into two groups according the median value of lean body mass to body weight (LBM/BW %) evaluated at first month. Age, sex, serum creatinine, albumin, and normalized protein catabolic rate (nPCR) were the independent determinants for LBM/BW%. The patient survival (68 vs 94 months ) and technique survival (55 vs 65 months) were longer in the higher LBM/BW%. Besides, peritonitis incidence, hospitalization episodes and hospitalization stay duration were lower in the higher LBM/BW% groups. The LBM/BW% is also the independent determinant for technique and patient survival after adjustment of age, diabetes, sex. In conclusion, initial LBM/BM% can predict PD patients and technique survival. Since the LBM/BW% is easily obtained in the routine PD clearance measurement and can reflect the real nutrition status, this parameter could be used extendedly to predict PD outcomes.

This study aimed to determine the factors that were associated with hypoalbuminemia in peritoneal dialysis (PD) patients. End-stage renal disease patients who had received PD at the National Taiwan University Hospital for more than three months were included and divided into two groups. Patients who had mean serum albumin levels greater or equal to 3.5 g/dL were allocated to Group 1, while those who had mean serum albumin levels less than 3.5 g/dL were allocated to Group 2. Demographic characteristics, clinical parameters and laboratory data were then compared between the two groups. Logistic regression was also performed to identify the factors that were associated with hypoalbuminemia. There were 359 patients (mean age 54.3 years, male 46.5%) included. Group 2 patients (10.3%) were older (P=0.0536), had lower body mass index (P=0.0008), lower total Kt/V (P=0.0060), and lower levels of hemoglobin (P=0.0268), blood urea nitrogen (P=0.0501), creatinine (P

Excessive fibrin deposition in the peritoneum is thought to be involved in the development of encapsulating peritoneal sclerosis (EPS), an important cause of morbidity and mortality in peritoneal dialysis patients. We investigated fibrin-induced epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) as a possible mechanism of fibrin involvement in EPS. In vitro, fibrin overlay of PMCs altered their morphology; increased α-smooth muscle actin, fibronectin, fibroblast specific protein-1, and α(v)β(3) integrin expression; and decreased cytokeratin 18 and E-cadherin expression. Fibrin overlay also increased focal adhesion kinase and Src kinase phosphorylation. Fibrin-induced changes were inhibited by treating the cells with α(v)β(3) integrin antibody or pentoxifylline (PTX). In a rat model, intraperitoneal injection of Staphylococcus aureus and fibrinogen induced severe EPS features, which were attenuated by PTX treatment. PTX-treated rats also showed preserved peritoneal ultrafiltration function and lower concentrations of cytokines than the untreated rats. S. aureus- and fibrinogen-injected rats had higher percentage of cytokeratin-positive cells in the omentum fibrotic tissue than controls; this was also reduced by PTX treatment. Our results suggest that fibrin induces EMT of PMCs by engaging α(v)β(3) integrin and activating associated kinases. Our EPS animal model showed that fibrin-induced EMT was involved in the pathogenesis of peritoneal fibrosis and was inhibited by PTX.

BACKGROUND: Effects of long-term glucose load on peritoneal dialysis (PD) patient safety and outcomes have seldom been reported. This study demonstrates the influence of long-term glucose load on patient and technique survival. METHODS: We surveyed 173 incident PD patients. Long-term glucose load was evaluated by calculating the average dialysate glucose concentration since initiation of PD. Risk factors were assessed by fitting Cox's models with repeatedly measured time-dependent covariates. RESULTS: We noted that older age, higher glucose concentration, and lower residual renal function (RRF) were significantly associated with a worse patient survival. We found that female gender, absence of diabetes, lower glucose concentration, use of icodextrin, higher serum high density lipoprotein cholesterol, and higher RRF were significantly associated with a better technique survival. CONCLUSIONS: Long-term glucose load predicted mortality and technique failure in chronic PD patients. These findings emphasize the importance of minimizing glucose load in PD patients.

BACKGROUND: Postoperative acute kidney injury (AKI) is associated with poor outcomes in surgical patients. This study aims to evaluate whether the timing of renal replacement therapy (RRT) initiation affects the in-hospital mortality of patients with postoperative AKI. METHODOLOGY: This multicenter retrospective observational study, which was conducted in the intensive care units (ICUs) in a tertiary hospital (National Taiwan University Hospital) and its branch hospitals in Taiwan between January, 2002, and April, 2009, included adult patients with postoperative AKI who underwent RRT for predefined indications. The demographic data, comorbid diseases, types of surgery and RRT, and the indications for RRT were documented. Patients were categorized according to the period of time between the ICU admission and RRT initiation as the early (EG, ≦1 day), intermediate (IG, 2-3 days), and late (LG, ≧4 days) groups. The in-hospital mortality rate censored at 180 day was defined as the endpoint. RESULTS: Six hundred forty-eight patients (418 men, mean age 63.0±15.9 years) were enrolled, and 379 patients (58.5%) died during the hospitalization. Both the estimated probability of death and the in-hospital mortality rates of the three groups represented U-curves. According to the Cox proportional hazard method, LG (hazard ratio, 1.527; 95% confidence interval, 1.152-2.024; P = 0.003, compared with IG group), age (1.014; 1.006-1.021), diabetes (1.279; 1.022-1.601; P = 0.031), cirrhosis (2.147; 1.421-3.242), extracorporeal membrane oxygenation support (1.811; 1.391-2.359), initial neurological dysfunction (1.448; 1.107-1.894; P = 0.007), pre-RRT mean arterial pressure (0.988; 0.981-0.995), inotropic equivalent (1.006; 1.001-1.012; P = 0.013), APACHE II scores (1.055; 1.037-1.073), and sepsis (1.939; 1.536-2.449) were independent predictors of the in-hospital mortality (All P