Late creation of vascular access increased post-hemodialysis mortality, hospitalization, and health-care expenditure: A population-based cohort study in Taiwan.

BACKGROUND/PURPOSE: The optimal timing of vascular access (VA) creation for hemodialysis (HD) and whether this timing affects mortality and health-care utilization after HD initiation remain unclear. Thus, we conducted a population-based study to explore their association. METHODS: We used Taiwan's National Health Insurance Research Database to analyze health-care outcomes and utilization in a cohort initiating HD during 2003-2013. We stratified patients by the following VA creation time points: >180, 91-180, 31-90, and ≤30 days before and ≤30 days after HD initiation and examined all-cause mortality, ambulatory care utilization/costs, hospital admission/costs, and total expenditure within 2 years after HD. Cox regression, Poisson regression, and general linear regression were used to analyze mortality, health-care utilization, and costs respectively. RESULTS: We identified 77,205 patients who started HD during 2003-2013. Compared with the patients undergoing VA surgery >180 days before HD initiation, those undergoing VA surgery ≤30 days before HD initiation had the highest mortality-15.92 deaths per 100-person-years, crude hazard ratio (HR) 1.56, and adjusted HR 1.28, the highest hospital admissions rates- 2.72 admission per person-year, crude rate ratio (RR) 1.48 and adjusted RR 1.32, and thus the highest health-care costs- US$31,390 per person-year, 7% increase of costs and 6% increase with adjustment within the 2-year follow-up after HD initiation. CONCLUSIONS: Late VA creation for HD can increase all-cause mortality, hospitalization, and health-care costs within 2 years after HD initiation. Early preparation of VA has the potential to reduce post-HD mortality and healthcare expenses for the ESKD patients.

A 24-year longitudinal study of Klebsiella pneumoniae isolated from patients with bacteraemia and urinary tract infections reveals the association between capsular serotypes, antibiotic resistance, and virulence gene distribution.

Longitudinal studies on the variations of phenotypic and genotypic characteristics of K. pneumoniae across two decades are rare. We aimed to determine the antimicrobial susceptibility and virulence factors for K. pneumoniae isolated from patients with bacteraemia or urinary tract infection (UTI) from 1999 to 2022. A total of 699 and 1,267 K. pneumoniae isolates were isolated from bacteraemia and UTI patients, respectively, and their susceptibility to twenty antibiotics was determined; PCR was used to identify capsular serotypes and virulence-associated genes. K64 and K1 serotypes were most frequently observed in UTI and bacteraemia, respectively, with an increasing frequency of K20, K47, and K64 observed in recent years. entB and wabG predominated across all isolates and serotypes; the least frequent virulence gene was htrA. Most isolates were susceptible to carbapenems, amikacin, tigecycline, and colistin, with the exception of K20, K47, and K64 where resistance was widespread. The highest average number of virulence genes was observed in K1, followed by K2, K20, and K5 isolates, which suggest their contribution to the high virulence of K1. In conclusion, we found that the distribution of antimicrobial susceptibility, virulence gene profiles, and capsular types of K. pneumoniae over two decades were associated with their clinical source.

Trajectory of Humoral Responses to Two Doses of ChAdOx1 nCoV-19 Vaccination in Patients Receiving Maintenance Hemodialysis.

The ChAdOx1 nCoV-19 (AZD1222) vaccine is one of the most commonly delivered SARS-CoV-2 vaccines worldwide; however, few clinical studies have investigated its immunogenicity in dialysis patients. We prospectively enrolled 123 patients on maintenance hemodialysis at a medical center in Taiwan. All patients were infection-naive, had received two doses of the AZD1222 vaccine, and were monitored for 7 months. The primary outcomes were anti-SARS-CoV-2 receptor-binding domain (RBD) antibody concentrations before and after each dose and 5 months after the second dose and neutralization capacity against ancestral SARS-CoV-2, delta, and omicron variants. The anti-SARS-CoV-2 RBD antibody titers significantly increased with time following vaccination, with a peak at 1 month after the second dose (median titer, 498.8 U/mL; interquartile range, 162.5 to 1,050 U/mL), and a 4.7-fold decrease at 5 months. At 1 month after the second dose, 84.6, 83.7, and 1.6% of the participants had neutralizing antibodies against the ancestral virus, delta variant, and omicron variant, respectively, measured by a commercial surrogate neutralization assay. The geometric mean 50% pseudovirus neutralization titers for the ancestral virus, delta variant, and omicron variant were 639.1, 264.2, and 24.7, respectively. The anti-RBD antibody titers correlated well with neutralization capacity against the ancestral virus and delta variant. Transferrin saturation and C-reactive protein were associated with neutralization against the ancestral virus and delta variant. Although two doses of the AZD1222 vaccine initially elicited high anti-RBD antibody titers and neutralization against the ancestral virus and delta variant in hemodialysis patients, neutralizing antibodies against omicron variant were rarely detected, and the anti-RBD and neutralization antibodies waned over time. Additional/booster vaccinations are warranted in this population. IMPORTANCE Patients with kidney failure have worse immune response following vaccination compared to general population, but few clinical studies have investigated immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccination in hemodialysis patients. Here, we showed two doses of AZD1222 vaccines lead to high seroconversion rate of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies, and more than 80% patients acquired neutralizing antibodies against ancestral virus and delta variant. However, seldom did they obtain neutralizing antibodies against the omicron variant. The geometric mean 50% pseudovirus neutralization titer against the ancestral virus was 25.9-fold higher than that against the omicron variant. Also, there was a substantial decay in anti-RBD titers with time. Our findings provided evidence supporting that more protective measures, including additional/booster vaccinations, is warranted in these patients during the current COVID-19 pandemic.

Effect of dialysis modalities on risk of hospitalization for gastrointestinal bleeding.

Dialysis patients are at risk of both thromboembolic and bleeding events, while thromboembolism prevention and treatment may confer a risk of major bleeding. Gastrointestinal (GI) bleeding is a great concern which can result in high subsequent mortality rates. Our object was to clarify whether hemodialysis (HD) and peritoneal dialysis (PD) confer different incidence of GI bleeding, and further assist individualized decision-making on dialysis modalities. We conducted a population-based retrospective cohort study which included all incident dialysis patients above 18 years old derived from the National Health Insurance database from 1998 to 2013 in Taiwan. 6296 matched pairs of HD and PD patients were identified. A propensity score matching method was used to minimize the selection bias. The adjusted hazard ratio for GI bleeding was 1.13 times higher in the HD group than in the PD group, and data from the unmatched cohort and the stratified analysis led to similar results. Among subgroup analysis, we found that the use of anticoagulants will induce a much higher incidence of GI bleeding in HD patients as compared to in PD patients. We concluded that PD is associated with a lower GI bleeding risk than HD, and is especially preferred when anticoagulation is needed.

Seasonal Change in Home Blood Pressure Monitoring Is Associated With Renal Outcome and Mortality in Patients With Chronic Kidney Disease.

Background: Blood pressure (BP) variation may result in poor cardiovascular and renal outcomes. We investigated the pattern of seasonal BP change and its association with outcomes in patients with chronic kidney disease (CKD) living in southern Taiwan. Methods: We conducted a retrospective analysis of a prospective observational cohort consisting of outpatients with CKD for the period between December 2014 and December 2019. These patients were grouped according to the pattern of seasonal BP variation, namely, consistently higher average systolic BP (≥8 mmHg) in wintertime than summertime (Group A), consistently lower average systolic BP (≥8 mmHg) in wintertime than summertime (Group B), large variation of average systolic BP (≥8 mmHg) without a specific pattern related to weather (Group C), and little fluctuation of average systolic BP (<8 mmHg) throughout the years (Group D). The study endpoints were ≥40% reduction in estimated glomerular filtration rate (eGFR), end stage renal disease (initiation of dialysis or transplantation), or death. Results: We analyzed 507 eligible patients, of whom 17.2% exhibited consistent BP elevation in the wintertime. There were 56.8% of patients conducting regular home BP monitoring. Cox regression analysis showed home BP monitoring was independently associated with better outcome in 507 CKD patients (HR 0.72, 95% CI 0.56-0.94, P = 0.0162). Compared with the other three groups, patients with BP elevation in the wintertime (Group A) were older, had a higher prevalence of diabetic nephropathy and nephrotoxic agent use, a lower prevalence of statin use, higher eGFR decline rate, and a worse outcome. Patients with BP reduction in the wintertime (Group B) were associated with the best outcome. Cox regression analysis indicated that consistent BP elevation in the wintertime in 288 CKD patients with home BP monitoring was significantly associated with a worse composite outcome (i.e., ≥40% reduction in eGFR, end stage renal disease, or death) after adjustment for various confounding factors. Conclusion: Home BP monitoring is crucial, and associated with better outcome in CKD patients. Consistent home BP elevation from summertime to wintertime in patients with CKD was associated with a poorer composite outcome.

The use of activated vitamin D and risks of hospitalization for infection and amputation in incident hemodialysis patients in Taiwan: a nationwide population-based cohort study.

BACKGROUND: Hemodialysis patients have a high risk of mortality. The most common causes of death are cardiovascular disease and infection. The potential hazard or benefit associated with vitamin D use and cardiovascular or infection outcome is poorly characterized. METHODS: We conducted a retrospective observational cohort study by recruiting 52,757 patients older than 20 years from Taiwan National Health Insurance Research Database (NHIRD) who initiated maintenance hemodialysis between 2001 and 2009. Patients who were prescribed activated vitamin D before the 360th day from hemodialysis initiation were defined as vitamin D users. The primary outcome of interest includes occurrence of acute myocardial infarction (AMI), ischemic stroke, lower limb amputation, and hospitalization for infection, respectively, while death events are treated as competing events. We conducted competing risk analysis using subdistribution hazard regression model to estimate subdistribution hazard ratios (SHRs) in relation to various outcomes. RESULTS: During the median follow-up of 1019 days, the vitamin D users had a lower crude mortality rate, lower incidences of AMI, ischemic stroke, amputation, and hospitalization for infection compared with non-users. Taking into consideration competing events of death, vitamin D users were associated with a lower hazard of lower limb amputation (SHR 0.84 [95% CI, 0.74-0.96]) and hospitalization for infection (SHR 0.90 [95% CI, 0.87-0.94]), but not AMI or ischemic stroke, after adjustment for potential confounders. Subgroup analyses and dose response evaluation both showed a consistent association of activated vitamin D treatment with decreased risk of amputation and infection. CONCLUSION: The findings suggest that therapeutic activated vitamin D use in hemodialysis patients may be beneficial for decreasing infection events and amputation, of which the latter is a complication of peripheral vascular disease, rather than reducing major atherosclerotic cardiovascular events such as AMI or ischemic stroke.

Serum sclerostin levels are positively related to bone mineral density in peritoneal dialysis patients: a cross-sectional study.

BACKGROUND: Sclerostin, an antagonist of the Wingless-type mouse mammary tumor virus integration site (Wnt) pathway that regulates bone metabolism, is a potential contributor of chronic kidney disease (CKD)-mineral and bone disorder (MBD), which has various forms of presentation, from osteoporosis to vascular calcification. The positive association of sclerostin with bone mineral density (BMD) has been demonstrated in CKD and hemodialysis (HD) patients but not in peritoneal dialysis (PD) patients. This study assessed the association between sclerostin and BMD in PD patients. METHODS: Eighty-nine PD patients were enrolled; their sera were collected for measurement of sclerostin and other CKD-MBD-related markers. BMD was also assessed simultaneously. We examined the relationship between sclerostin and each parameter through Spearman correlation analysis and by comparing group data between patients with above- and below-median sclerostin levels. Univariate and multiple logistic regression models were employed to define the most predictive of sclerostin levels in the above-median category. RESULTS: Bivariate analysis revealed that sclerostin was correlated with spine BMD (r = 0.271, P = 0.011), spine BMD T-score (r = 0.274, P = 0.010), spine BMD Z-score (r = 0.237, P = 0.027), and intact parathyroid hormone (PTH; r = - 0.357, P < 0.001) after adjustments for age and sex. High BMD, old age, male sex, increased weight and height, diabetes, and high osteocalcin and uric acid levels were observed in patients with high serum sclerostin levels and an inverse relation was noticed between PTH and sclerostin. Univariate logistic regression analysis demonstrated that BMD is positively correlated with above-median sclerostin levels (odds ratio [OR] = 65.61, P = 0.002); the correlation was retained even after multivariate adjustment (OR = 121.5, P = 0.007). CONCLUSIONS: For the first time, this study demonstrated a positive association between serum sclerostin levels and BMD in the PD population.

Assessing the effect of oral activated vitamin D on overall survival in hemodialysis patients: a landmark analysis.

BACKGROUND: Patients with end stage renal disease have a high all-cause and cardiovascular mortality. Secondary hyperparathyroidism and vitamin D deficiency are considered part of the mechanism for the excess mortality observed. We aimed to evaluate the relationship between vitamin D use and all-cause mortality. METHODS: In this retrospective cohort study, we included all incident patients who started hemodialysis in Taiwan between 2001 and 2009. Patients were followed from landmark time, i.e., the 360th day from hemodialysis initiation, through the end of 2010 or death. We evaluated the association between activated vitamin D use or not before landmark time and all-cause mortality using conditional landmark analysis with Cox regression. We used group-based trajectory model to categorize high-dose versus average-dose users to evaluate dose-response relationships. RESULTS: During the median follow-up of 1019 days from landmark time, vitamin D users had a lower crude mortality rate than non-users (8.98 versus 12.93 per 100 person-years). Compared with non-users, vitamin D users was associated with a lower risk of death in multivariate Cox model (HR 0.91 [95% CI, 0.87-0.95]) and after propensity score matching (HR 0.94 [95% CI, 0.90-0.98]). High-dose vitamin D users had a lower risk of death than conventional-dose users, HR 0.75 [95% CI, 0.63-0.89]. The association of vitamin D treatment with reduced mortality did not alter when we re-defined landmark time as the 180th day or repeated analyses in patients who underwent hemodialysis in the hospital setting. CONCLUSIONS: Our findings supported the survival benefits of activated vitamin D among incident hemodialysis patients.

Clinical and microbiological characteristics of peritoneal dialysis-related peritonitis caused by Escherichia coli in southern Taiwan.

Peritonitis is a serious complication and major cause of treatment failure in patients undergoing peritoneal dialysis (PD). Escherichia coli is the major pathogen in extraintestinal Gram-negative infections, including PD-related peritonitis. The outcomes of E. coli peritonitis in PD varied from relatively favorable outcomes to a higher incidence of treatment failure. The aim of this study was to investigate the impact of bacterial virulence and host characteristics on the outcomes of PD-related peritonitis caused by E. coli. From January 2000 to June 2016, a total of 47 episodes of monomicrobial and 10 episodes of polymicrobial E. coli PD-related peritonitis, as well as 89 episodes of monomicrobial Gram-positive (56 Staphylococcus spp. and 33 Streptococcus spp.) PD-related peritonitis cases, were retrospectively enrolled. Clinical features, E. coli bacterial virulence, and outcomes were analyzed. Compared to Streptococcus spp. peritonitis, E. coli peritonitis had a higher peritoneal catheter removal rate (38 versus 12%; P = 0.0115). Compared to the monomicrobial group, patients in polymicrobial group were older and had higher peritoneal catheter removal rate (80 versus 38%; P = 0.0324). Treatment failure of E. coli peritonitis was associated with more polymicrobial peritonitis and immunocompromised comorbidity, longer duration of PD therapy, and more antimicrobial resistance. E. coli isolates with more iron-related genes had higher prevalence of phylogenetic group B2 and papG II, iha, ompT, and usp genes. This study demonstrates the important roles of clinical and bacterial characteristics in the outcomes of monomicrobial and polymicrobial E. coli PD-related peritonitis.

A Cohort Study of Adult Patients with Severe Dengue in Taiwanese Intensive Care Units: The Elderly and APTT Prolongation Matter for Prognosis.

BACKGROUND: There was a large dengue outbreak in Taiwan in 2015, in which the ages of the affected individuals were higher than those in other countries. The aim of this study was to explore the characteristics and prognostic factors for adults with severe dengue in intensive care units (ICUs). METHODS: All adults admitted to ICUs with dengue virus infection (DENV) at a medical center from July 1, 2015 to December 31, 2015 were enrolled. DENV was diagnosed by the presence of serum NS1 antigen, IgM antibodies to dengue virus, or dengue virus RNA by real-time reverse transcriptase polymerase chain reaction. Demographic data, clinical features, and lab data were collected, and a multivariate Cox model was used to identify the predictive factors for in-hospital mortality. RESULTS: Seventy-five patients admitted to ICUs with laboratory-confirmed DENV were enrolled (mean age 72.3±9.3 years). The most common comorbidities included hypertension (72.0%), diabetes (43.7%), and chronic kidney disease (22.7%). The in-hospital case fatality rate (CFR) was 41.3%. The patients who died were predominantly female, had higher disease severity at ICU admission, shorter ICU/hospital stay, longer initial activated partial thromboplastin time (APTT), and higher initial serum aspartate transaminase levels. Cardiac arrest before ICU admission (hazard ratio [HR]: 6.26 [1.91-20.54]), prolonged APTT (>48 seconds; HR: 3.91 [1.69-9.07]), and the presence of acute kidney injury on admission (HR: 2.48 [1.07-5.74]), were independently associated with in-hospital fatality in the Cox multivariate analysis. CONCLUSION: During the 2015 dengue outbreak in Taiwan, the patients with severe dengue in ICUs were characterized by old age, multiple comorbidities, and a high CFR. Organ failure (including cardiac failure, and renal failure) and coagulation disturbance (prolongation of initial APTT) were independent predictive factors for in-hospital fatality.

Association Between Vascular Access Dysfunction and Subsequent Major Adverse Cardiovascular Events in Patients on Hemodialysis: A Population-Based Nested Case-Control Study.

The association between dialysis vascular access dysfunction and the risk of developing major adverse cardiovascular events (MACE) in hemodialysis patients is unclear and has not yet been investigated. We analyzed data from the National Health Insurance Research Database of Taiwan to quantify this association. Adopting a case-control design nested within a cohort of patients who received hemodialysis from 2001 to 2010, we identified 9711 incident cases of MACE during the stage of stable maintenance dialysis and 19,422 randomly selected controls matched to cases on age, gender, and duration of dialysis. Events of vascular access dysfunction in the 6-month period before the date of MACE onset (ie, index date) for cases and before index dates for controls were evaluated retrospectively. The presence of vascular access dysfunction was associated with a 1.385-fold higher odds of developing MACE as estimated from the logistic regression analysis. This represents a significantly increased adjusted odds ratio (OR) at 1.268 (95% confidence interval [CI] = 1.186-1.355) after adjustment for comorbidities and calendar years of initiating dialysis. We also noted a significant exposure-response trend (P < 0.001) between the frequency of vascular access dysfunction and MACE, with the greatest risk (adjusted OR = 1.840, 95% CI = 1.549-2.186) noted in patients with ≥3 vascular access events. We concluded that dialysis vascular access dysfunction was significantly associated with an increased risk of MACE. Hence, vascular access failure can be an early sign for MACE in patients receiving maintenance hemodialysis. Active monitoring and treatment of cardiovascular risk factors and related diseases, not merely managing vascular access dysfunction, would be required to reduce the risk of MACE.