Extremely Low Dose of Erythropoiesis-Stimulating Agent May Be Associated with Increased Mortality in Hemodialysis Patients.

INTRODUCTION: Although high-dose erythropoiesis-stimulating agent (ESA) has been shown to increase mortality risk and adverse cardiovascular events in hemodialysis patients, the safety of extremely low-dose ESA is unclear. METHODS: We retrospectively analyzed the association between ESA dose and mortality in the monthly dosing range of 0-43,000 U of equivalent epoetin alfa in 304 Taiwan hemodialysis patients by using Cox proportional hazard model and cubic spline model. RESULTS: Compared with mean monthly ESA dose of 15,000-25,000 U (mean ± standard deviation 20,609 ± 2,662 U), monthly ESA dose of less than 15,000 U (mean ± standard deviation 7,413 ± 4,510 U) is associated with increased mortality. Monthly ESA dose of 25,001-43,000 U (mean ± standard deviation 31,160 ± 4,304 U) is not associated with higher mortality risk than monthly ESA dose of 15,000-25,000 U. The results were consistent in Cox proportional hazard models and cubic spline models. Subgroup analyses showed no significant heterogeneities among prespecified subgroups. CONCLUSIONS: Extremely low dose of ESA in hemodialysis patients may be associated with increased mortality risk. Future studies are warranted to prove this association.

Short-Term Effects of a Therapeutic Diet on Biochemical Parameters in Hemodialysis Patients: A Randomized Crossover Trial.

OBJECTIVE: Although unhealthy diets exacerbate nutritional and metabolic derangements in patients with end-stage kidney disease (ESKD), how therapeutic diets that possess a variety of different dietary strategies acutely modify diverse biochemical parameters related to cardiovascular disease remains underexplored. METHODS: Thirty-three adults with end-stage kidney disease undergoing thrice-weekly hemodialysis participated in a randomized crossover trial comparing a therapeutic diet with their usual diets for 7 days, separated by a 4-week washout period. The therapeutic diet was characterized by adequate calorie and protein amounts, natural food ingredients with a low phosphorus-to-protein ratio, higher portions of plant-based food, and high fiber content. The primary outcome measure was the mean difference in the change-from-baseline intact fibroblast growth factor 23 (FGF23) level between the 2 diets. The other outcomes of interest included changes in mineral parameters, uremic toxins, and high-sensitivity C-reactive protein (hs-CRP) levels. RESULTS: Compared with the usual diet, the therapeutic diet lowered intact FGF23 levels (P = .001), decreased serum phosphate levels (P < .001), reduced intact parathyroid hormone (PTH) levels (P = .003), lowered C-terminal FGF23 levels (P = .03), increased serum calcium levels (P = .01), and tended to lower total indoxyl sulfate levels (P = .07) but had no significant effect on hs-CRP levels. Among these changes, reduction in serum phosphate level achieved in 2 days, modifications of intact PTH and calcium levels in 5 days, and reductions in intact and C-terminal FGF23 levels in 7 days of therapeutic diet intervention. CONCLUSION: Within the 1-week intervention period, the dialysis-specific therapeutic diet rapidly reversed mineral abnormalities and tended to decrease total indoxyl sulfate levels in patients undergoing hemodialysis but had no effect on inflammation. Future studies to assess the long-term effects of such therapeutic diets are recommended.

Adverse events following the first, second and third doses of a COVID-19 vaccine in hemodialysis patients.

BACKGROUND: This study aimed to identify adverse events following the first three doses of COVID-19 vaccines in hemodialysis (HD) patients. Risk factors associated with postvaccination adverse events were explored. METHODS: Postvaccination adverse events in 438 HD patients who received 3 doses of COVID-19 vaccines were prospectively assessed. The adverse events among three doses were compared using generalized linear mixed models. Factors associated with adverse events were assessed with multivariate analyses. RESULTS: The vast majority of participants received Oxford/AstraZeneca ChAdOx1 as their first two doses and Moderna mRNA-1273 as their third dose. Overall, 79%, 50% and 84% of the participants experienced at least one adverse event after their first, second, and third doses, respectively. These adverse events were mostly minor, short-lived and less than 5% reported daily activities being affected. Compared with the first dose, the second dose caused a lower rate of adverse events. Compared with the first dose, the third dose elicited a higher rate of injection site reactions and a lower rate of systemic reactions. Multivariate analyses showed that every 10-year increase of age (odds ratio 0.67, 95% confidence intervals 0.57-0.79) was associated with decreased risk of adverse events, while female sex (2.82, 1.90-4.18) and arteriovenous fistula (1.73, 1.05-2.84) were associated with increased risk of adverse events. Compared with Oxford/AstraZeneca ChAdOx1, Moderna mRNA-1273 was associated with an increased risk of injection site reactions. CONCLUSIONS: COVID-19 vaccination was well tolerated in HD patients. Age, sex, dialysis vascular access and vaccine types were associated with postvaccination adverse events.

Altered Monocytic Phenotypes are Associated with Uraemic Pruritus in Patients Receiving Haemodialysis.

Uraemic pruritus is one of the most bothersome symptoms in patients receiving haemodialysis. A total of 175 patients receiving maintenance haemodialysis, with 74 patients experiencing uraemic pruritus, were prospectively recruited to assess the influence of the phenotype of blood monocytes and various cytokines on uraemic pruritus. The phenotype of blood monocytes was determined by flow cytometry as classical (CD14++CD16-) monocytes, non-classical (CD14+CD16++) monocytes, and intermediate (CD14++CD16+) monocytes. Eight cyto-kines, including interleukin (IL)-2, interferon-γ, IL-12p70, IL-4, IL-5, IL-6, tumour necrosis factor-α, and IL-10, were simultaneously detected with a multi-plex bead-based immunoassay. Multivariate linear regression analysis showed that a higher percentage of intermediate monocytes (effect estimate 0.08; 95% confidence interval 0.01-0.16) were independent predictors of a higher visual analogue scale score for pruritus intensity. No differences were noted for all 8 cytokines between patients with and without uraemic pruritus. The results of this study indicate that altered monocytic phenotypes could play a role in uraemic pruritus.

Acute effects of dietary phosphorus intake on markers of mineral metabolism in hemodialysis patients: post hoc analysis of a randomized crossover trial.

BACKGROUND: Long-term dietary phosphorus excess influences disturbances in mineral metabolism, but it is unclear how rapidly the mineral metabolism responds to short-term dietary change in dialysis populations. METHODS: This was a post hoc analysis of a randomized crossover trial that evaluated the short-term effects of low-phosphorus diets on mineral parameters in hemodialysis patients. Within a 9-day period, we obtained a total of 4 repeated measurements for each participant regarding dietary intake parameters, including calorie, phosphorus, and calcium intake, and markers of mineral metabolism, including phosphate, calcium, intact parathyroid hormone (iPTH), intact fibroblast growth factor 23 (iFGF23), and C-terminal fibroblast growth factor 23 (cFGF23). The correlations between dietary phosphorus intake and serum mineral parameters were assessed by using mixed-effects models. RESULTS: Thirty-four patients were analyzed. In the fully adjusted model, we found that an increase in dietary phosphorus intake of 100 mg was associated with an increase in serum phosphate of 0.3 mg/dL (95% confidence intervals [CI], 0.2-0.4, p < .001), a decrease in serum calcium of 0.06 mg/dL (95% CI, -0.11 to -0.01, p = .01), an increase in iPTH of 5.4% (95% CI, 1.4-9.3, p = .01), and an increase in iFGF23 of 5.0% (95% CI, 2.0-8.0, p = .001). Dietary phosphorus intake was not related to cFGF23. CONCLUSIONS: Increased dietary phosphorus intake acutely increases serum phosphate, iPTH, and iFGF23 levels and decreases serum calcium levels, highlighting the important role of daily fluctuations of dietary habits in disturbed mineral homeostasis in hemodialysis patients.

Prediction of the development of acute kidney injury following cardiac surgery by machine learning.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a major complication that results in increased morbidity and mortality after cardiac surgery. Most established prediction models are limited to the analysis of nonlinear relationships and fail to fully consider intraoperative variables, which represent the acute response to surgery. Therefore, this study utilized an artificial intelligence-based machine learning approach thorough perioperative data-driven learning to predict CSA-AKI. METHODS: A total of 671 patients undergoing cardiac surgery from August 2016 to August 2018 were enrolled. AKI following cardiac surgery was defined according to criteria from Kidney Disease: Improving Global Outcomes (KDIGO). The variables used for analysis included demographic characteristics, clinical condition, preoperative biochemistry data, preoperative medication, and intraoperative variables such as time-series hemodynamic changes. The machine learning methods used included logistic regression, support vector machine (SVM), random forest (RF), extreme gradient boosting (XGboost), and ensemble (RF + XGboost). The performance of these models was evaluated using the area under the receiver operating characteristic curve (AUC). We also utilized SHapley Additive exPlanation (SHAP) values to explain the prediction model. RESULTS: Development of CSA-AKI was noted in 163 patients (24.3%) during the first postoperative week. Regarding the efficacy of the single model that most accurately predicted the outcome, RF exhibited the greatest AUC (0.839, 95% confidence interval [CI] 0.772-0.898), whereas the AUC (0.843, 95% CI 0.778-0.899) of ensemble model (RF + XGboost) was even greater than that of the RF model alone. The top 3 most influential features in the RF importance matrix plot were intraoperative urine output, units of packed red blood cells (pRBCs) transfused during surgery, and preoperative hemoglobin level. The SHAP summary plot was used to illustrate the positive or negative effects of the top 20 features attributed to the RF. We also used the SHAP dependence plot to explain how a single feature affects the output of the RF prediction model. CONCLUSIONS: In this study, machine learning methods were successfully established to predict CSA-AKI, which determines risks following cardiac surgery, enabling the optimization of postoperative treatment strategies to minimize the postoperative complications following cardiac surgeries.

Effects of lower versus higher phosphate diets on fibroblast growth factor-23 levels in patients with chronic kidney disease: a systematic review and meta-analysis.

Background: Elevated fibroblast growth factor-23 (FGF23) levels increase the risk of cardiovascular diseases in patients with chronic kidney disease (CKD). We aimed to compare the effects of different dietary interventions, lower versus higher phosphate levels, on FGF23 in patients with CKD. Methods: We conducted electronic literature searches of Medline, PubMed, Embase and the Cochrane Library for publications up to 29 October 2016 for randomized clinical trials that compared lower versus higher phosphate dietary interventions in adults with CKD. The primary outcome was the difference in change-from-baseline FGF23 levels between intervention groups. Considering the difference in measurement units between intact FGF23 and C-terminal FGF23 assays, the treatment effect was analysed as the standardized mean difference (SMD) with the 95% confidence interval (CI). Results: We identified five trials enrolling a total of 94 normophosphataemic patients with Stage 3B CKD. The study duration ranged from 1 to 12 weeks. Compared with higher phosphate diets, lower phosphate diets tended to reduce FGF23 levels (SMD -0.74, 95% CI -1.54 to 0.07, P = 0.07). Subgroup analyses showed a trend (P for interaction = 0.09) towards a better FGF23-lowering effect by lower phosphate diets in studies using the intact FGF23 assay (SMD -1.14, 95% CI -2.24 to -0.04) than those using the C-terminal FGF23 assay (SMD -0.05, 95% CI -0.67 to 0.57). Conclusions: Short-term dietary phosphate restriction tends to reduce FGF23 levels in patients with moderately decreased kidney function, and the FGF23-lowering effects tend to be more prominent when measured with the intact FGF23 assay.

Anti-cytomegalovirus IgG antibody titer is positively associated with advanced T cell differentiation and coronary artery disease in end-stage renal disease.

BACKGROUND: Accumulating evidence indicates that persistent human cytomegalovirus (HCMV) infection is associated with several health-related adverse outcomes including atherosclerosis and premature mortality in individuals with normal renal function. Patients with end-stage renal disease (ESRD) exhibit impaired immune function and thus may face higher risk of HCMV-related adverse outcomes. Whether the level of anti-HCMV immune response may be associated with the prognosis of hemodialysis patients is unknown. RESULTS: Among 412 of the immunity in ESRD study (iESRD study) participants, 408 were HCMV seropositive and were analyzed. Compared to 57 healthy individuals, ESRD patients had higher levels of anti-HCMV IgG. In a multivariate-adjusted logistic regression model, the log level of anti-HCMV IgG was independently associated with prevalent coronary artery disease (OR = 1.93, 95% CI = 1.2~ 3.2, p = 0.01) after adjusting for age, sex, hemoglobin, diabetes, calcium phosphate product and high sensitivity C-reactive protein. Levels of anti-HCMV IgG also positively correlated with both the percentage and absolute number of terminally differentiated CD8+ and CD4+ CD45RA+ CCR7- TEMRA cells, indicating that immunosenescence may participate in the development of coronary artery disease. CONCLUSION: This is the first study showing that the magnitude of anti-HCMV humoral immune response positively correlates with T cell immunosenescence and coronary artery disease in ESRD patients. The impact of persistent HCMV infection should be further investigated in this special patient population.

Pretreatment of Sialic Acid Efficiently Prevents Lipopolysaccharide-Induced Acute Renal Failure and Suppresses TLR4/gp91-Mediated Apoptotic Signaling.

BACKGROUND/AIMS: Lipopolysaccharides (LPS) binding to Toll-like receptor 4 (TLR4) activate NADPH oxidase gp91 subunit-mediated inflammation and oxidative damage. Recognizing the high binding affinity of sialic acid (SA) with LPS, we further explored the preventive potential of SA pretreatment on LPS-evoked acute renal failure (ARF). METHODS: We determined the effect of intravenous SA 30 min before LPS-induced injury in urethane-anesthetized female Wistar rats by evaluating kidney reactive oxygen species (ROS) responses, renal and systemic hemodynamics, renal function, histopathology, and molecular mechanisms. RESULTS: LPS time-dependently reduced arterial blood pressure, renal microcirculation, and increased blood urea nitrogen and creatinine in the rats. LPS enhanced monocyte/macrophage infiltration and ROS production, and subsequently impaired kidneys with the enhancement of TLR4/NADPH oxidase gp91/Caspase 3/poly-(ADP-ribose)-polymerase (PARP)-mediated apoptosis in the kidneys. SA pretreatment effectively alleviated LPS-induced ARF. The levels of LPS-increased ED-1 infiltration and ROS production in the kidney were significantly depressed by SA pretreatment. Furthermore, SA pretreatment significantly depressed TLR4 activation, gp91 expression, and Caspase 3/PARP induced apoptosis in the kidneys. CONCLUSION: We suggest that pretreatment of SA significantly and preventively attenuated LPS-induced detrimental effects on systemic and renal hemodynamics, renal ROS production and renal function, as well as, LPS-activated TLR4/gp91/Caspase3 mediated apoptosis signaling.

Comparing long-term outcomes between early and delayed initiation of peritoneal dialysis following catheter implantation.

AIM: The aim of this study was to compare peritonitis rates, peritoneal dialysis technique survival and patient survival between patients who started peritoneal dialysis earlier than 14 days (early starters) and 14 days or more (delayed starters) after insertion of a Tenckhoff catheter. METHODS: Observational analysis was performed for all patients who underwent insertion of a Tenckhoff catheter at Far Eastern Memorial Hospital between 1 January 2006 and 31 December 2012. The patients were divided into two groups: early and delayed starters. The rate and outcomes of peritonitis were recorded. Peritoneal dialysis technique survival and patient survival were analyzed using the Kaplan-Meier method. Cox regression analysis was performed for peritoneal dialysis technique failure and patient mortality. RESULTS: There were 80 early starters and 69 delayed starters. The peritonitis rate was 0.18 episodes per year in early starters and 0.13 episodes per year in delayed starters. There was no significant difference of peritonitis free survival (p = 0.146), peritoneal dialysis technique survival (p = 0.273) and patient survival (p = 0.739) at 1, 3, 5 years between early starters and delayed starters. After adjustment with age, albumin and diabetes, early starters did not have an increased risk of peritonitis, technique failure and mortality compared to delayed starters. CONCLUSION: Compared to the patients who started peritoneal dialysis 14 days or more after catheter implantation, the patients who started earlier did not have an increased risk of peritonitis, peritoneal dialysis technique failure and mortality.

Visceral adiposity index and risks of cardiovascular events and mortality in prevalent hemodialysis patients.

BACKGROUND: The visceral adiposity index (VAI) is a newly-derived measure of visceral adiposity with well-validated predictive power for cardiovascular (CV) outcomes in the general population. However, this predictability has not been investigated in hemodialysis patients, and whether VAI is superior to waist circumference (WC) and waist-to-height ratio (WHtR) in predicting CV outcomes and survival in hemodialysis patients remains unknown. METHODS: We performed a prospective study including 464 prevalent hemodialysis patients. The composite outcome was the occurrence of death and CV events during follow-up. Using multivariate Cox regression analysis, VAI, WC and WHtR were tested for the predictive power of outcomes. To evaluate the predictive performance of the VAI, WC and WHtR, time-dependent receiver operating characteristic curve (ROC) analysis was performed. RESULTS: VAI, WC and WHtR positively correlated with each other. Patients with a higher VAI (tertile 3 vs. tertile 1, adjusted hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.12-2.42; tertile 2 vs. tertile 1, adjusted HR, 1.52; 95% CI, 1.1-2.18) had more composite outcomes. VAI had a similar predictive power of all-cause mortality to WC and WHtR, but superior predictive power of composite and CV outcomes to WC when analyzed by a stepwise forward likelihood ratio test. In time-dependent ROC analysis, VAI, WC and WHtR showed similar predictive performance for outcomes. CONCLUSION: VAI is an optimal method to measure visceral adiposity to assess long-term CV outcomes and all-cause mortality in prevalent hemodialysis patients. VAI may provide a superior predictive power of CV outcomes to WC and WHtR. TRIAL REGISTRATION: ClinicalTrials.gov NCT01457625.

Fetuin A/nutritional status predicts cardiovascular outcomes and survival in hemodialysis patients.

BACKGROUND: Fetuin A - a predictor of cardiovascular (CV) outcomes in dialysis patients - is correlated with over-nutrition in the general population. Whether fetuin A and nutritional status interact with each other to alter CV outcomes and survival in hemodialysis (HD) patients remains unknown. METHODS: We performed a prospective study on 388 prevalent HD patients. We used the geriatric nutritional risk index (GNRI) for the evaluation of nutritional status. Study outcomes included the occurrence of CV event, CV death, and all-cause mortality during follow-up; interactions between parameters for predicting outcomes were assessed by the interaction terms in a Cox regression model. RESULTS: Overall, 131 patients experienced CV events and 92 patients died, with 51 CV deaths. HD patients with higher fetuin A levels had lower numbers of CV events (adjusted hazard ratio [HR], 0.9; 0.81-0.99) and all-cause mortality (adjusted HR, 0.97; 0.91-0.99). However, patients with higher GNRI had lower all-cause mortality (adjusted HR, 0.79; 0.51-0.98, for every 10-unit increase). Fetuin A levels and GNRI showed a significant interaction in the prediction of CV events (adjusted HR, 1.01; 1.008-1.02) but not for all-cause or CV mortality. In patients with poor nutritional status, higher fetuin A levels were associated with fewer CV events; however, in contrast, in subjects with better nutritional status, higher fetuin A levels appeared to lead to a higher number of CV events. CONCLUSIONS: Fetuin A showed a remarkable interaction with nutritional status in evaluating the risks of CV morbidities in prevalent HD patients.

Interleukin-31 is associated with uremic pruritus in patients receiving hemodialysis.

BACKGROUND: Interleukin (IL)-31 induces severe pruritus and dermatitis in transgenic mice, and is associated with many itching skin diseases. OBJECTIVE: We sought to investigate the association of serum IL-31 levels with uremic pruritus in patients undergoing hemodialysis. METHODS: Patients receiving maintenance hemodialysis in a referral medical center were recruited. Serum IL-31 levels were determined by the enzyme-linked immunosorbent assay methodology. The various characteristics of pruritus were assessed using an interview questionnaire. RESULTS: Among the 178 study participants, 34.8% had uremic pruritus. The patients with pruritus had higher serum IL-31 levels than those without pruritus symptoms (median 8.68 [first quartile 0.43, third quartile 35.04] vs 4.91 [0, 15.78], P = .04). A multivariate linear regression analysis showed that higher serum levels of IL-31, high-sensitivity C-reactive protein, and alanine transaminase, and a lower dialysis dose assessed by Kt/V, were independent predictors for higher pruritus intensity. The generalized additive model also showed a positive exposure-response relationship between serum levels of IL-31 and visual analog scale scores of pruritus intensity. LIMITATIONS: The cause-effect relationship between IL-31 and uremic pruritus could not be assessed by the cross-sectional study design. CONCLUSION: IL-31 may play an important role in the pathophysiology of uremic pruritus.

Liver fat contents, abdominal adiposity and insulin resistance in non-diabetic prevalent hemodialysis patients.

BACKGROUND: The liver fat contents and abdominal adiposity correlate well with insulin resistance (IR) in the general population. However, the relationship between liver fat content, abdominal adiposity and IR in non-diabetic hemodialysis (HD) patients remains unclear. This study aimed to clarify the associations among these factors. METHODS: This is a cross-sectional, observational study. All patients received abdominal ultrasound for liver fat content. Abdominal adiposity was quantified with the conicity index (Ci) and waist circumference (WC). We checked the homeostasis model assessment for insulin resistance index (HOMA-IR) for IR. RESULTS: A total of 112 patients (60 women) were analyzed. Subjects with higher liver fat contents and WC had higher IR indices. But Ci did not correlate with IR indices. In both the multi-variable linear regression model and the logistic regression model, only higher liver fat content predicted a severe IR status. CONCLUSIONS: Liver fat contents have a remarkable correlation with IR; however, abdominal adiposity, measured either by Ci or WC, dose not independently correlate with IR in non-diabetic prevalent HD patients.

Percutaneous Coronary Intervention With a Drug-Eluting Stent Versus Coronary Artery Bypass Grafting in Patients Receiving Dialysis: A National Study From Taiwan.

Rationale & Objective: We aimed to study the comparative effectiveness of percutaneous coronary intervention with drug-eluting stent and coronary artery bypass grafting in patients receiving dialysis. Study Design: This was a retrospective observational cohort study. Setting & Participants: This population-based study identified patients receiving dialysis hospitalized for coronary revascularization between January 1, 2009 and December 31, 2015, in the Taiwan National Health Insurance Research Database. Exposures: Patients received percutaneous coronary intervention with drug-eluting stent versus coronary artery bypass grafting. Outcomes: The study outcomes were all-cause mortality, in-hospital mortality, and repeat revascularization. Analytical Approach: Propensity scores were used to match patients. Cox proportional hazards models and logistic regression models were constructed to examine associations between revascularization strategies and mortality. Interval Cox models were fitted to estimate time-varying hazards during different periods. Results: A total of 1,840 propensity score-matched patients receiving dialysis were analyzed. Coronary artery bypass grafting was associated with higher in-hospital mortality (coronary artery bypass grafting vs percutaneous coronary intervention with drug-eluting stent; crude mortality rate 12.5% vs 3.3%; adjusted OR, 5.22; 95% CI, 3.42-7.97; P < 0.001) and longer hospitalization duration (median [IQR], 20 [14-30] days vs 3 [2-8] days; P < 0.001). After discharge, repeat revascularization, acute coronary syndrome, and repeat hospitalization all occurred more frequently in the percutaneous coronary intervention with drug-eluting stent group. Importantly, with a median follow-up of 2.8 years, coronary artery bypass grafting was significantly associated with a higher risk of all-cause overall mortality (adjusted HR, 1.19; 95% CI, 1.05-1.35; P = 0.006) in the multivariable Cox proportional hazard model. Sensitivity and subgroup analyses yielded consistent results. Limitations: This was an observational study with mainly Asian ethnicity. Conclusions: Percutaneous coronary intervention with drug-eluting stent may be associated with better survival than coronary artery bypass grafting in patients receiving dialysis. Future studies are warranted to confirm this finding.

Although coronary artery bypass grafting offers better long-term survival in the general population than percutaneous coronary intervention with drug-eluting stent, patients receiving dialysis may be too frail to tolerate the increased perioperative mortality risk of coronary artery bypass grafting. In this retrospective study in a national cohort of patients receiving dialysis from Taiwan, percutaneous coronary intervention with drug-eluting stent is associated with lower in-hospital mortality and better long-term survival when compared with coronary artery bypass grafting. Subsequent acute coronary syndrome, repeat revascularization, and rehospitalization were noted more frequently in the percutaneous coronary intervention with drug-eluting stent group. These findings may suggest percutaneous coronary intervention with drug-eluting stent as a safe revascularization strategy for patients receiving dialysis.

Low serum fetuin A levels and incident stroke in patients with maintenance haemodialysis.

BACKGROUND AND OBJECTIVES: Fetuin A, a predictor of mortality in dialysis patients, is associated with vascular calcification and atherosclerosis in haemodialysis (HD) patients. Whether it predicts stroke remains unknown. This study aimed to investigate the association between fetuin A and incident stoke in maintenance HD patients. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: This is a prospective observational study. 238 prevalent HD patients (127 women and 111 men; mean age, 60 ± 12 years) were followed up for the occurrence of stroke for 55 months. Baseline circulating fetuin A levels, biochemical data and other markers of inflammation were measured. The major outcome was the occurrence of incident ischaemic or haemorrhagic stroke. RESULTS: Thirty one patients had incident strokes; an incidence of 38·4/1000 patient-years (95% confidence interval (CI) 36·5-39·8/1000 patient-years) on follow-up. Patients in the lowest tertile of fetuin A concentration had highest risk to have incident stroke (P < 0·001, log-rank test). By Cox proportional-hazards regression, patients with higher fetuin A levels experienced lower incidence of stroke, hazard ratio (HR) of 0·89 (95% CI, 0·84-0·96), while those with higher mean arterial blood pressure had an HR of 1·19 (95% CI, 1·07-1·34) and those with higher calcium phosphate product (CaxP) had an HR of 1·39 (95% CI, 1·1-1·73) for having strokes. For patients without previous history of diabetes and cerebrovascular disease, fetuin A deficiency also predicts the occurrence of incident stroke. CONCLUSIONS: Fetuin A deficiency is associated with a higher risk of incident stroke among prevalent HD patients.

Short- and long-term impact of subtotal parathyroidectomy on the achievement of bone and mineral parameters recommended by clinical practice guidelines in dialysis patients: a 12-year single-center experience.

BACKGROUND/AIMS: The short- and long-term impact of parathyroidectomy (PTX) on the parameters of mineral bone disease in dialysis patients with severe secondary hyperparathyroidism (HPT) remains unclear. METHODS: A retrospective chart review of 401 consecutive dialysis patients who underwent subtotal PTX by one surgeon was performed. We checked serum levels of calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) for 3 consecutive days, and then monthly for Ca, P, and tri-monthly for iPTH postoperatively. Patients with available laboratory data within the 1st to 6th postoperative months were included in the short-term follow-up group and those with at least 6 months available data were in the long-term follow-up one. RESULTS: Patients (short-term group, n = 401, and long-term group, n = 94) had severely uncontrolled serum iPTH levels, Ca, P and Ca × P before PTX. In the short-term group, percentages of cases achieving K/DOQI targets for serum Ca, Ca × P, and iPTH and KDIGO ones for serum Ca, P, and iPTH after PTX, significantly improved compared with those before operation (all p < 0.05). In the long-term group (mean follow-up of 43 ± 29 months), the percentage of achieved targets for serum iPTH in both guidelines and for serum Ca and Ca × P in the K/DOQI recommendation also improved postoperatively (all p < 0.05). CONCLUSIONS: Achievements of K/DOQI recommended values for serum Ca, Ca × P, iPTH and KDIGO recommendations for iPTH can be successfully reached by subtotal PTX in medically refractory, secondary HPT in dialysis patients both during short- and long-term follow-ups.

Sodium thiosulfate through preserving mitochondrial dynamics ameliorates oxidative stress induced renal apoptosis and ferroptosis in 5/6 nephrectomized rats with chronic kidney diseases.

Chronic kidney disease (CKD) progression may be evoked through dysregulated mitochondrial dynamics enhanced oxidative stress and inflammation contributing to high cardiovascular morbidity and mortality. Previous study has demonstrated sodium thiosulfate (STS, Na2S2O3) could effectively attenuate renal oxidative injury in the animal model of renovascular hypertension. We explored whether the potentially therapeutic effect of STS is available on the attenuating CKD injury in thirty-six male Wistar rats with 5/6 nephrectomy. We determined the STS effect on reactive oxygen species (ROS) amount in vitro and in vivo by an ultrasensitive chemiluminescence-amplification method, ED-1 mediated inflammation, Masson's trichrome stained fibrosis, mitochondrial dynamics (fission and fusion) and two types of programmed cell death, apoptosis and ferroptosis by western blot and immunohistochemistry. Our in vitro data showed STS displayed the strongest scavenging ROS activity at the dosage of 0.1 g. We applied STS at 0.1 g/kg intraperitoneally 5 times/week for 4 weeks to these CKD rats. CKD significantly enhanced the degree in arterial blood pressure, urinary protein, BUN, creatinine, blood and kidney ROS amount, leukocytes infiltration, renal 4-HNE expression, fibrosis, dynamin-related protein 1 (Drp1) mediated mitochondrial fission, Bax/c-caspase 9/c-caspase 3/poly (ADP-ribose) polymerase (PARP) mediated apoptosis, iron overload/ferroptosis and the decreased xCT/GPX4 expression and OPA-1 mediated mitochondrial fusion. STS treatment significantly ameliorated oxidative stress, leukocyte infiltration, fibrosis, apoptosis and ferroptosis and improved mitochondrial dynamics and renal dysfunction in CKD rats. Our results suggest that STS as drug repurposing strategy could attenuate CKD injury through the action of anti-mitochondrial fission, anti-inflammation, anti-fibrosis, anti-apoptotic, and anti-ferroptotic mechanisms.

Microbiota analysis in the hemodialysis population - Focusing on Enterobacteriaceae.

BACKGROUND: Infection is a recognized risk factor for mortality among hemodialysis (HD) population, including infection caused by Enterobacteriaceae. We aimed to investigate Enterobacteriaceae in gut microbiota among HD patients and to analyze associations between microbiota and clinical parameters. METHODS: This prospective study of microbiota analysis in HD patients was conducted in April-May 2019. A control group without recent antibiotic use or hospitalization was used for comparison. Stool samples underwent 16S rRNA sequencing, using Greengenes 16S rRNA database for microbiota analysis. RESULTS: Among 96 hemodialysis (HD) patients, mean age was 61.9 ± 0.8 years and mean duration of HD was 6.5 ± 0.7 years. No significant differences were found in alpha diversity between HD and control groups (HD group 949.5, controls 898; p = 0.16) although significant between-group differences were found in beta diversity (p < 0.001). At phylum level, HD group had a higher abundance of Firmicutes and Proteobacteria, but lower abundance of Bacteriodetes. At genus level, Escherichia-Shigella complex increased among HD patients who had hospitalization with 1 year (median 0.024 vs 0.004, p = 0.054) and Klebsiella was associated with emergency room visit within 1 year among HD patients (p = 0.002). CONCLUSIONS: Alpha diversity in HD patients is not lower than that in healthy controls but significant between-group differences are found in microbiota composition according to beta diversity, due to decreased Bacteriodetes and increased Firmicutes and Proteobacteria. Deeper microbiota analyses for Enterobacteriaceae are necessary. Whether change in dietary components can help to decrease mortality among dialysis population warrants further research.

Physician Compliance With a Computerized Clinical Decision Support System for Anemia Management of Patients With End-stage Kidney Disease on Hemodialysis: Retrospective Electronic Health Record Observational Study.

BACKGROUND: Previous studies on clinical decision support systems (CDSSs) for the management of renal anemia in patients with end-stage kidney disease undergoing hemodialysis have previously focused solely on the effects of the CDSS. However, the role of physician compliance in the efficacy of the CDSS remains ill-defined. OBJECTIVE: We aimed to investigate whether physician compliance was an intermediate variable between the CDSS and the management outcomes of renal anemia. METHODS: We extracted the electronic health records of patients with end-stage kidney disease on hemodialysis at the Far Eastern Memorial Hospital Hemodialysis Center (FEMHHC) from 2016 to 2020. FEMHHC implemented a rule-based CDSS for the management of renal anemia in 2019. We compared the clinical outcomes of renal anemia between the pre- and post-CDSS periods using random intercept models. Hemoglobin levels of 10 to 12 g/dL were defined as the on-target range. Physician compliance was defined as the concordance of adjustments of the erythropoietin-stimulating agent (ESA) between the CDSS recommendations and the actual physician prescriptions. RESULTS: We included 717 eligible patients on hemodialysis (mean age 62.9, SD 11.6 years; male n=430, 59.9%) with a total of 36,091 hemoglobin measurements (average hemoglobin and on-target rate were 11.1, SD 1.4, g/dL and 59.9%, respectively). The on-target rate decreased from 61.3% (pre-CDSS) to 56.2% (post-CDSS) owing to a high hemoglobin percentage of >12 g/dL (pre: 21.5%; post: 29%). The failure rate (hemoglobin <10 g/dL) decreased from 17.2% (pre-CDSS) to 14.8% (post-CDSS). The average weekly ESA use of 5848 (SD 4211) units per week did not differ between phases. The overall concordance between CDSS recommendations and physician prescriptions was 62.3%. The CDSS concordance increased from 56.2% to 78.6%. In the adjusted random intercept model, the post-CDSS phase showed increased hemoglobin by 0.17 (95% CI 0.14-0.21) g/dL, weekly ESA by 264 (95% CI 158-371) units per week, and 3.4-fold (95% CI 3.1-3.6) increased concordance rate. However, the on-target rate (29%; odds ratio 0.71, 95% CI 0.66-0.75) and failure rate (16%; odds ratio 0.84, 95% CI 0.76-0.92) were reduced. After additional adjustments for concordance in the full models, increased hemoglobin and decreased on-target rate tended toward attenuation (from 0.17 to 0.13 g/dL and 0.71 to 0.73 g/dL, respectively). Increased ESA and decreased failure rate were completely mediated by physician compliance (from 264 to 50 units and 0.84 to 0.97, respectively). CONCLUSIONS: Our results confirmed that physician compliance was a complete intermediate factor accounting for the efficacy of the CDSS. The CDSS reduced failure rates of anemia management through physician compliance. Our study highlights the importance of optimizing physician compliance in the design and implementation of CDSSs to improve patient outcomes.