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BACKGROUND An unconventional risk factor, "dysfunction of hemodialysis vascular access", was demonstrated to be associated with subsequent major adverse cardiovascular events (MACE) in our previous study. However, applying this suggestion in a clinical scenario may be not intuitive. A group-based trajectory model was applied to further recognize those patients with the highest risks for MACE.Methods and Results:In a cohort of patients who received hemodialysis from 2001 to 2010, we identified 9,711 cases that developed MACE in 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 MACE for cases and index dates for controls were evaluated. By group-based trajectory modeling, patients according to their counts of vascular access dysfunction in each month over the 6-month period prior to MACE or index dates were categorized. There were 26,744 patients in group 1 (no dysfunction), 650 in group 2 (escalating dysfunction) and 1,739 in group 3 (persistent dysfunction). Logistic regression analysis indicated that patients in group 3 had the highest chance of subsequent MACE (odds ratio 2.47, in comparison with group 1) after controlling for all the available potential confounders. CONCLUSIONS Uninterrupted clusters of vascular access dysfunction are associated with a higher risk of subsequent MACE.

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 (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.

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.

Introduction Occult hepatitis B virus (HBV) infection, defined as negative hepatitis B surface antigen (HBsAg) but detectable HBV DNA in serum and liver tissue, has very rarely been described in cryoglobulinemia (CG) patients. This case report sheds light on the possible link between occult HBV infection and CG. Patient concerns A 76-year-old man presented with rapidly deteriorating renal function within 1 year. Diagnosis Cryoglobulinemic glomerulonephritis was diagnosed through renal biopsy. Initially, the patient tested negative for HBsAg, but a low HBV viral load was later discovered, indicating an occult HBV infection. Further studies also revealed Waldenstrom macroglobulinemia (WM). Interventions We treated the patient as WM using plasma exchange and rituximab-based immunosuppressive therapy. Outcomes After 1 cycle of immunosuppressive treatment, there was no improvement of renal function. Shortly after, treatment was discontinued due to an episode of life-threatening pneumonia. Hemodialysis was ultimately required. Conclusion Future studies are needed to explore the link between occult HBV infection and CG, to investigate the mediating role of lymphomagenesis, and to examine the effectiveness of anti-HBV drugs in treating the group of CG patients with occult HBV infection. We encourage clinicians to incorporate HBV viral load testing into the evaluation panel for CG patients especially in HBV-endemic areas, and to test HBV viral load for essential CG patients in whom CG cannot be attributed to any primary disease.

Aim To assess the relationship between acarbose and hepatotoxicity, cardiovascular disease (CVD), and mortality among type 2 diabetes (T2D) patients with end-stage renal disease (ESRD). Methods 32,531 T2D patients with ESRD were identified from Taiwan’s National Health Insurance Research Database in 2000~∼2012 and followed up until 2013. 19.3% of subjects were newly initiated with acarbose during the follow-up. The use of acarbose was quantified as the numbers of the 30-day drug’s supplies and dosages (measured by defined daily doses; DDDs), respectively. Time-varying Cox models were applied to evaluate the association of acarbose use with hepatic, cardiovascular and mortality outcomes, with adjustment for patients’ demographics, comorbidities, diabetes severity, and co-medications. Results For each 30-day supply increase in acarbose exposure, the risks of hepatic injury, composite CVD events, and all-cause mortality were significantly lowered by 9% (95% confidence interval: 6–12%), 7% (6–7%) and 7% (7–8%), respectively, while for each 30-day DDD increase in acarbose exposure, the risks for three aforementioned outcomes were significantly reduced by 45% (33–54%), 33% (29–36%) and 35% (32–39%), respectively. In subgroup analyses, the favorable study outcomes of acarbose use were more apparent among patients with more severe diabetes, a longer diabetes duration, or absence of established CVD at baseline. Conclusion Acarbose used in real-world T2D patients with ESRD may have hepatic and cardiovascular safety.

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

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. Electronic supplementary material The online version of this article (10.1186/s12882-018-1111-2) contains supplementary material, which is available to authorized users.

Background: The relationship between type 1 diabetes mellitus (T1DM) and cancer incidence remains unclear. We sought to assess the all-cause and site-specific cancer incidence in patients with T1DM. Methods: A retrospective cohort study design was employed, in which 14 619 patients with T1DM were retrieved from Taiwan’s National Health Insurance medical claims between 2000 and 2007. The study subjects were followed to the end of 2008, and cancer incidence was assessed. We calculated age-, sex-, and calendar year-standardized incidence ratios (SIRs) of all-cause cancer incidence and site-specific neoplasm incidence, with reference to the general population. Results: Seven hundred and sixty patients were identified for all-cause cancer over 86 610 person-years, representing an incidence rate of 87.75 cases per 10 000 person-years. The incidence rate was higher in males than in female patients (109.86 vs 69.75 cases per 10 000 person-years). T1DM was associated with a significantly increased SIR of all-cause cancer (1.13; 95% confidence interval [CI], 1.05–1.22). The sex-specific SIR was significantly elevated in female patients (1.19; 95% CI, 1.07–1.33), but the SIR for male patients was insignificantly elevated (1.09; 95% CI, 0.99–1.20). Pancreatic cancer showed the greatest increase in SIR among both male and female patients with T1DM. Male patients experienced significantly increased SIRs for kidney, rectum, liver, and colon neoplasm, and significantly increased SIRs were noted for ovarian, bladder, and colon cancer in female patients. Conclusions: T1DM was associated with a 13% increase in risk of all-cause cancer incidence. Patients with T1DM should be advised to undergo cancer screening for certain types of cancer.

Background: Compliance index derived from digital volume pulse (CI-DVP), measuring the relationship between volume and pressure changes in fingertip, is a surrogate marker of peripheral arterial stiffness. This study investigated if CI-DVP can predict renal function deterioration, cardiovascular events and mortality in patients with chronic kidney disease (CKD). Methods: In this prospective observational study, 149 CKD patients were included for final analysis. CI-DVP and brachial-ankle pulse wave velocity (baPWV) were measured, decline in renal function was assessed by the estimated glomerular filtration rate (eGFR) slope. Composite renal and cardiovascular outcomes were evaluated, including ≥50% eGFR decline, start of renal replacement therapy, and major adverse events. Results: Patients in CKD stages 3b to 5 had higher baPWV and lower CI-DVP values than those in patients with CKD stages 1 to 3a. Stepwise multivariate linear regression analysis showed that lower CI-DVP (p =0.0001) and greater proteinuria (p =0.0023) were independent determinants of higher eGFR decline rate. Multivariate Cox regression analysis revealed that CI-DVP (HR 0.68, 95% CI 0.46-1.00), baseline eGFR (HR 0.96, 95% CI 0.94-0.98) and serum albumin (HR 0.17, 95% CI 0.07-0.42) were independent predictors for composite renal and cardiovascular outcomes. Conclusions: Compliance index, CI-DVP, was significantly associated with renal function decline in patients with CKD. A higher CI-DVP may have independent prognostic value in slower renal function decline and better composite renal and cardiovascular outcomes in CKD patients.

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., Author Summary Severe forms of dengue fever (DF) are usually considered as a pediatric disease in southern Asia and are graded from dengue hemorrhagic fever (DHF) to dengue with shock syndrome (DSS). However, the age of affected individuals is increasing in Singapore, Thailand, Mainland China, Taiwan and many other countries. Limited data are available on the elderly with DF in intensive care units (ICUs). DF in the elderly is an emerging infectious disease and poses a new clinical challenge to physicians. We enrolled the patients with laboratory-confirmed dengue in our ICU during the 2015 dengue outbreak in Taiwan. These patients were characterized by old age, multiple comorbidities, and a high case fatality rate (CFR). All of the patients were classified as severe dengue, and the in-hospital CFR was 41.3%. Renal failure and cardiac arrest were associated with fatality. In addition to organ failure, initial prolonged activated partial thromboplastin time (APTT) in our study was consistent with an independent predictive factor for in-hospital fatality. Previous studies have also reported that prolongation of APTT is a clinical predictor of dengue virus infection (DENV) or DHF. Our results highlight that APTT prolongation may be a prognostic factor in critically ill adults with severe dengue.

Aim End-stage renal disease (ESRD) is a common finding in systemic lupus erythematosus (SLE) and may contribute to mortality. The purpose of the study was to investigate the incidence of ESRD and all-cause mortality and their risk factors in patients newly diagnosed with SLE in Taiwan. Methods This nationwide cohort study used data from the National Health Insurance Research Database. We identified 4130 newly diagnosed SLE patients at risk for ESRD during 2000–2002; among them, 103 developed ESRD by the end of 2008. Additional 412 age- and sex-matched incident ESRD non-SLE patients served as controls for the survival analysis. Results Of the newly diagnosed SLE patients, 2.5% developed ESRD. Age (adjusted hazards ratio [HR] 0.66 for each 1-year increase; 95% confidence interval [CI] 0.47–0.94) and male gender (adjusted HR 2.24; 95% CI 1.4–3.6) were significantly associated with ESRD development. Survival analysis conducted after ESRD development revealed a higher mortality risk among the older patients (HR 1.04; 95% CI 1.02–1.05). Survival analysis in the younger population (age

Annual influenza vaccination is recommended, but its efficacy in dialysis population is still controversial. Here we aimed to compare the dynamic changes of immune response between various influenza vaccination protocols in hemodialysis patients. A 18-week open label, non-randomized, controlled trial was conducted during 2011–2012. The efficacy between unvaccinated, one- and two-dose regimens were evaluated in 175 hemodialysis patients. Immunogenic profiles were assessed by hemagglutination-inhibition assays. At 3–9 weeks post-vaccination, antibody responses were similar between the one- and two-dose regimens, while the seroprotection rates (antibody titer ≥1:40) for influenza A were 55.6–82.5% in the adult (18–60 years) and 33.3–66.7% in the elderly (>60 years). Meanwhile, the seroprotection rates for influenza B were low (4.0–25.0%). By 18 weeks post-vaccination, the seroprotection rates for influenza A and B declined (0.0–33.3%) in both the adult and elderly receiving one- or two-dose regimens. Of dialysis patients, at most 2.4% developed moderate to severe adverse effects(myalgia and headache) after vaccination. In conclusion, the two-dose regimen could not improve immune responses than the one-dose regimen in hemodialysis patients; meanwhile the induced protective antibodies of both regimens could not be maintained for more than 4 months. Modification of current influenza vaccination strategy in dialysis population should be re-considered.

Parathyroidectomy is recommended by the clinical guidelines for dialysis patients with unremitting secondary hyperparathyroidism (SHPT). However, the survival advantage of parathyroidectomy is debated because of the selection bias in previous studies. To minimize potential bias in the present nationwide cohort study, we enrolled only dialysis patients who had undergone radionuclide parathyroid scanning to ensure all patients had severe SHPT. The parathyroidectomized patients were matched with the controls based on propensity score for parathyroidectomy. Mortality hazard was estimated using multivariate Cox proportional hazard models adjusting for comorbidities before scanning (model 1) or over the whole study period (model 2). Our results showed that among the 2786 enrolled patients, 1707 underwent parathyroidectomy and the other 1079 were controls. The crude mortality rates were lower in the parathyroidectomized patients than in the controls. In adjusted analyses for the population matched on propensity score, parathyroidectomy was associated with a significant 20% to 25% lower risk for all-cause mortality (model 1: hazard ratio 0.76, 95% confidence interval 0.61 to 0.94; model 2: hazard ratio 0.80, 95% confidence internal 0.64 to 0.98). We concluded that parathyroidectomy was associated with a reduced long-term mortality risk in dialysis patients with severe SHPT.

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

Supplemental Digital Content is available in the text, The aim of our study was to estimate the risk of end-stage renal disease (ESRD) in type 1 diabetes mellitus (T1DM) in Taiwanese people; in addition, our goal was to determine how the age, year, and sex at registration of T1DM affects the risk. Population-based cohort study. A nationwide cohort study of 7203 Taiwanese patients with T1DM registered in 1999 to 2010 was followed up until ESRD, death, or the end of follow-up on December 31, 2010. Annual age-, sex-, and calendar year-specific incidence rates of ESRD of the general population were used to calculate the standardized incidence ratio (SIR) of ESRD in relation to T1DM. The SIR of ESRD for male and female patients with T1DM was significantly increased at 25.85 (95% CI 23.40–28.29) and 28.08 (95% 25.45–30.71), respectively; the peak was at age 15 to 29 years for both genders. The cumulative incidence of ESRD was similar in male and female patients but was significantly higher in patients ≥ 30 years old than in patients