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Gram-positive (GP) pathogens are less accounted for in pediatric urinary tract infection (UTI), and their clinical impact is underrecognized. This study aimed to identify predictors of GP uropathogens in pediatric UTI. In this 14-year retrospective cohort of pediatric patients with UTI, we classified first-time UTIs cases into those caused by GP or Gram-negative (GN) bacteria. We constructed a multivariable logistic regression model to predict GP UTI. We evaluated model performance through calibration and discrimination plots. We developed a nomogram to predict GP UTI that is clinically feasible. Of 3783 children with first-time UTI, 166 (4.4%) were infected by GP and 3617 (95.6%) by GN bacteria. Among children with GP UTI, the most common uropathogens were vancomycin-resistant Enterococcus faecalis (VRE) (27.1%), Staphylococcus saprophyticus (26.5%), and coagulase-negative Staphylococci (12.7%). Eight independent risk factors were associated with GP UTI: Age ≥ 24 months (odds ratio [OR]: 3.21), no prior antibiotic use (OR: 3.13), serum white blood cell (WBC) count 3/μL (OR: 2.19), high sensitivity C-reactive protein (hsCRP) E. faecalis, the leading GP uropathogen causing pediatric UTI, requires early detection for infection control. Our model for predicting GP UTI can help clinicians detect GP uropathogens and administer antibiotic regimen early.

The role of the difference and ratio of albuminuria (urine albumin-to-creatinine ratio, uACR) and proteinuria (urine protein-to-creatinine ratio, uPCR) has not been systematically evaluated with all-cause mortality. We retrospectively analyzed 2904 patients with concurrently measured uACR and uPCR from the same urine specimen in a tertiary hospital in Taiwan. The urinary albumin-to-protein ratio (uAPR) was derived by dividing uACR by uPCR, whereas urinary non-albumin protein (uNAP) was calculated by subtracting uACR from uPCR. Conventional severity categories of uACR and uPCR were also used to establish a concordance matrix and develop a corresponding risk matrix. The median age at enrollment was 58.6 years (interquartile range 45.4–70.8). During the 12,391 person-years of follow-up, 657 deaths occurred. For each doubling increase in uPCR, uACR, and uNAP, the adjusted hazard ratios (aHRs) of all-cause mortality were 1.29 (95% confidence interval [CI] 1.24–1.35), 1.12 (1.09–1.16), and 1.41 (1.34–1.49), respectively. For each 10% increase in uAPR, it was 1.02 (95% CI 0.98–1.06). The linear dose–response association with all-cause mortality was only observed with uPCR and uNAP. The 3 × 3 risk matrices revealed that patients with severe proteinuria and normal albuminuria had the highest risk of all-cause mortality (aHR 5.25, 95% CI 1.88, 14.63). uNAP significantly improved the discriminative performance compared to that of uPCR (c statistics: 0.834 vs. 0.828, p-value = 0.032). Our study findings advocate for simultaneous measurements of uPCR and uACR in daily practice to derive uAPR and uNAP, which can provide a better mortality prognostic assessment.

Background/Purpose: Urinary tract infections (UTIs) are one of the most common pediatric infections. Our objective in this study is to investigate the association between urine pH and uropathogens in pediatric patients. Methods: The source population comprised 26 066 paired urinalysis (UA) and urine culture (UC) samples obtained from pediatric patients. We classified the paired UA–UC samples into UTI positive (N = 6348) and UTI negative (N = 19 718) according to the colony forming units corresponding to the sampling source. We included UTI positive patients with infection caused by a single species of pathogen (N = 5201) and frequency matched them with UTI negative patients (N = 4729) by age, sex, sampling source, and visit type. Results: This study included 5201 pediatric patients with UTIs and found that urine with Proteus mirabilis or Pseudomonas aeruginosa demonstrated the least acidic pH (mean pH = 6.72 and 6.62, respectively), whereas urine with Escherichia coli or Klebsiella pneumoniae exhibited the most acidic pH (pH = 6.21 and 6.18). After stratifying the UTI samples by their pH range (

Introduction: Sclerostin could enhance renal excretion of calcium (Ca) and phosphate (P). The association between sclerostin and magnesium (Mg) has not yet discovered. In patients with type 2 diabetes mellitus (T2DM) or chronic kidney disease (CKD), higher serum sclerostin and altered renal excretion of Ca, P, and Mg were detected. Therefore, we tried to evaluate if there was any association between sclerostin and fractional excretion of Ca, P, and Mg (FeCa, FeP, and FeMg) in T2DM with CKD. Methods: In this prospective cohort study, 43 T2DM patients without CKD or with CKD stage 1–5 were enrolled. Values of parameters, including serum and urine sclerostin, were collected at baseline and 6 months later. For baseline data, the Mann-Whitney U test, χ2 test, or Spearman’s correlation were used. For multivariate repeated measurement analysis, generalized estimating equation (GEE) model was utilized. Results: Patients with lower estimated glomerular filtration rate had higher serum sclerostin, FeP, FeMg, and lower FeCa. By correlation analysis, serum sclerostin was negatively associated with FeCa (p = 0.02) and positively associated with FeP (p = 0.002). The urine sclerostin to creatinine ratio (Uscl/Ucre) was positively correlated with FeP (p = 0.007) and FeMg (p = 0.005). After multivariate analyses by GEE model, serum sclerostin was still inversely associated with FeCa, while Uscl/Ucre was significantly associated with FeMg. On the other hand, FeP lost its associations with serum sclerostin or Uscl/Ucre. Conclusion: In our study population of T2DM patients with or without CKD, the inverse correlation between serum sclerostin and FeCa could not be explained by the calciuric effect of sclerostin. In addition, a newly discovered positive association between urinary sclerostin and FeMg indicated a possible role of urinary sclerostin in regulating renal Mg handling especially over distal convoluted tubules.

The effects of long-term disturbance of the mineral metabolism on patients with chronic kidney disease (CKD) are unclear. We investigated whether the longitudinal Ca-P (joint calcium and phosphorus) trajectories are associated with incident end-stage renal disease (ESRD), acute coronary syndrome (ACS), and all-cause mortality in patients with CKD. We conducted a prospective cohort study by using data from a 13-year multidisciplinary pre-ESRD care registry. The final study population consisted of 4,237 CKD patients aged 20–90 years with data gathered from 2003 to 2015. Individuals’ Ca-P trajectories were defined using group-based multi-trajectory modeling into three distinct patterns: reference, moderately abnormal, and severely abnormal. Times to ESRD, ACS, and death were analyzed using multiple Cox regression. Compared with those with a “reference” Ca-P trajectory, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) for incidental ESRD were 5.92 (4.71–7.44) and 15.20 (11.85–19.50) for “moderately abnormal” and “severely abnormal” Ca-P trajectories, respectively. The corresponding aHRs for ACS were 1.94 (1.49–2.52) and 3.18 (2.30–4.39), and for all-cause mortality, they were 1.88 (1.64–2.16) and 2.46 (2.05–2.96) for “moderately abnormal” and “severely abnormal” Ca-P trajectories, respectively. For outcomes of progression to ESRD, the detrimental effects of abnormal Ca-P trajectories were more substantial in patients with CKD stage 3 than those with CKD stage 4 or 5 (p-value for interaction < 0.001). Future studies should validate reliable longitudinal cut-offs of serum phosphorus and consider the “lowering phosphorus— the lower the better, the earlier the better” approach to phosphorus control in CKD.

Real-world evidence describing the variation in serum creatinine (S-Cre) within 24 hours and its prognostic value is unknown. We enrolled 14 912 adults who received two S-Cre measurements within 24 hours at a tertiary hospital between 2003 and 2016. The study population was divided into four groups according to the hospital service settings where the baseline and second S-Cre were measured: Group 1, Outpatient-to-Outpatient; Group 2, Outpatient-to-ED (emergency department) or Inpatient; Group 3, ED-to-ED or Inpatient; and Group 4, Inpatient-to-Inpatient. The main predictors were the difference between the two S-Cre measurements (ΔS-Cre) and the percent change (ΔS-Cre%). The main outcomes were 30-day, 1-year, or 3-year all-cause mortality. A total of 6753 and 8159 patients with an increase and a decrease within-day ΔS-Cre, respectively. Among 6753 patients who had deteriorating ΔS-Cre or ΔS-Cre%, the adjusted hazard ratio (aHR) for 1-year all-cause mortality for each 0.1 mg/dL or 5% change in S-Cre was 1.09 (95% confidence interval [CI]: 1.07, 1.11) and 1.03 (95% CI: 1.03, 1.04). In 8159 patients with improving ΔS-Cre%, the aHR was 0.97 (95% CI: 0.94, 1.00). Groups 3 and 4 had statistically significant positive linear relationships between deteriorating ΔS-Cre% and 30-day and 3-year mortality. The optimal cut-offs for deteriorating ΔS-Cre% for predicting 30-day mortality were approximately 22% for Group 3 and 20% for Group 4. Inpatient within-day deteriorating ΔS-Cre or ΔS-Cre% above 0.2 mg/dL or 20%, respectively, is associated with all-cause mortality. Monitoring 24-hour S-Cre variation identifies acute kidney injury earlier than the conventional criteria.

Key Points Question Is prenatal exposure to arsenic and other metals associated with the occurrence of atopic dermatitis in young children? Findings In this cohort study of 586 mother and child pairs, prenatal arsenic exposure was associated with approximately 2.4 times the occurrence of atopic dermatitis in children at age 4 years. In addition, coexposure to arsenic and cadmium was associated with increased odds of developing atopic dermatitis. Meaning The results of this study suggest that prevention of inorganic arsenic and cadmium exposure among pregnant women could reduce the risk of atopic dermatitis and other allergic diseases in children., Importance The prevalence of atopic dermatitis has substantially increased in recent decades, and atopic dermatitis could lead to allergic airway inflammation later in life. A previous study found that inorganic arsenic exposure was associated with allergic airway inflammation in children aged 8 to 14 years. However, the association between prenatal exposure to arsenic and other metals and the risk of atopic dermatitis among young children remains unknown. Objective To assess the association between prenatal exposure to arsenic and other metals and the occurrence of atopic dermatitis in children at age 4 years. Design, Setting, and Participants In total, 1152 pregnant women were enrolled in the original Taiwan Maternal and Infant Cohort Study (TMICS), a multicenter birth cohort study conducted at 9 hospitals in northern, central, southern, and eastern Taiwan from October 2012 to May 2015. Of those, 586 mothers and children aged 4 years participated in follow-up questionnaire interviews from August 2016 to January 2019. After excluding 216 participants with missing data, the final statistical analysis of follow-up data included 370 mother and child pairs from the central and eastern regions of Taiwan. Data were analyzed from February 2 to August 12, 2021. Exposures Arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc during pregnancy. Main Outcomes and Measures The outcome was parent-reported atopic dermatitis history among children aged 4 years. The presence of atopic dermatitis was defined as a positive response to the question, “Has your child ever had atopic dermatitis diagnosed by a physician?” During the initial TMICS study period, concentrations of arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc were measured in maternal urine during the third trimester of pregnancy using an inductively coupled plasma mass spectrometer. Estimated total inorganic arsenic exposure was calculated using a model that included data on both total arsenic and arsenic species (arsenite, arsenate, monomethylarsonate, and dimethylarsenate) obtained from a previous TMICS cohort. Results Among 370 children included in the analysis, the mean (SD) age was 3.94 (0.59) years; 208 children (56.2%) were male, and 267 children (72.2%) were from the central region of Taiwan. A total of 110 children (29.7%) had atopic dermatitis at age 4 years. Maternal estimated total inorganic arsenic exposure during pregnancy was associated with increased odds of atopic dermatitis among children at age 4 years (odds ratio [OR], 2.42 [95% CI, 1.33-4.39] for every doubled increase of total inorganic arsenic) after adjusting for parental allergies, child’s sex, geographic area, maternal educational level, and exposure to tobacco smoke. Every increased unit in the weighted quantile sum index of maternal metal exposure was significantly associated with atopic dermatitis (OR, 1.63; 95% CI, 1.28-2.07). Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal mixture index. Conclusions and Relevance This cohort study found that prenatal exposure to inorganic arsenic and coexposure to inorganic arsenic and cadmium were associated with a higher risk of atopic dermatitis in young children. These findings suggest that prevention of exposure to inorganic arsenic and cadmium during pregnancy may be helpful for the control of atopic dermatitis and other potential allergies in children., This cohort study examines the association between prenatal exposure to arsenic and other metals and the development of atopic dermatitis among young children in central and eastern Taiwan.

Studies on the effects of longitudinal lipid trajectories on end-stage renal disease (ESRD) development and deaths among patients with chronic kidney disease (CKD) are limited. We conducted a registry-based prospective study using data from a 13-year multidisciplinary pre-ESRD care program. The final study population comprised 4,647 patients with CKD. Using group-based trajectory modeling, we dichotomized longitudinal trajectories of total cholesterol (T-CHO), triglyceride (TG), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C). Time to ESRD or death was analyzed using multiple Cox regression. At baseline, higher levels of T-CHO and LDL-C were associated with rapid progression to ESRD, whereas only HDL-C was positively associated with all-cause mortality [adjusted hazard ratio (HR), 1.20; 95% CI, 1.06-1.36; P-value, 0.005]. Compared with those with a normal T-CHO trajectory, the fully adjusted HR of patients with a high T-CHO trajectory for ESRD risk was 1.21 (P-value, 0.019). Subgroup analysis showed that a high TG trajectory was associated with a 49% increase in mortality risk in CKD patients without diabetes (P-value for interaction, 0.012). In contrast to what was observed based on baseline HDL-C, patients with a trajectory of frequent hypo-HDL cholesterolemia had higher risk of all-cause mortality (adjusted HR, 1.53; P-value, 0.014). Thus, only T-CHO, both at baseline and over the longitudinal course, demonstrated a significant potential risk of incident ESRD. The inconsistency in the observed directions of association between baseline levels and longitudinal trajectories of HDL-C warrants further research to unveil specific pathogenic mechanisms underlying the HDL-C metabolism in patients with CKD.

The effect of low-moderate levels of arsenic exposure and of arsenic metabolism on mortality remains uncertain. We used data from a prospective cohort study in 3,600 men and women aged 45 to 75 years living in Arizona, Oklahoma, and North and South Dakota. The biomarker of inorganic arsenic exposure was the sum of urine inorganic (iAs), monomethylated (MMA) and dimethylated (DMA) arsenic compounds (ΣAs) at baseline. The proportions of urine iAs, MMA and DMA over the ΣiAs, expressed as iAs%, MMA%, and DMA%, respectively, were used as biomarkers of arsenic metabolism. Arsenic exposure and arsenic metabolism were associated with all-cause, cardiovascular, and cancer mortality. For each interquartile range (IQR) increase in ΣAs (12.5 μg/L, overall range 0.7-194.1 μg/L), the adjusted hazard ratios (aHRs) were 1.28 (95% CI 1.16-1.41) for all-cause mortality, 1.28 (1.08-1.52) for cardiovascular mortality and 1.15 (0.92-1.44) for cancer mortality. The aHR for mortality for each IQR increase in MMA%, when iAs% is decreasing, was 1.52 (95% CI 1.16-1.99) for cardiovascular disease, 0.73 (0.55-0.98) for cancer, and 1.03 (0.90-1.19) for all-cause mortality. These findings at low-moderate levels of arsenic exposure highlight the need to implement public health measures to protect populations from involuntary arsenic exposure and for research to advance the biological and clinical understanding of arsenic-related health effects in general populations.

Existing evidence revealed grave prognosis for cryptococcal meningitis (CM), particularly its short-term mortality. However, its long-term survival and prognostic factors remained unknown. This study investigated 3-year mortality and analyzed its predictive factors in patients with CM. This retrospective cohort study with 83 cerebrospinal fluid culture-confirmed CM patients was conducted at China Medical University Hospital from 2003 to 2016. The 3-year mortality rate in patients with CM was 54% (45 deaths among 83 patients). Advanced age, human immunodeficiency virus (HIV) seronegative state, low Glasgow Coma Scale score on admission, decreased hemoglobin and hyperglycemia on diagnosis were associated with 3-year mortality. After multivariate adjustment in the Cox proportional hazard model, only severe hyperglycemia (serum glucose ≥200 mg/dL) on diagnosis could predict 3-year mortality.

Continuity of care (COC) has been emphasized in research on terminal cancer patients to increase the quality of end-of-life care; however, limited research has been conducted on end-stage renal disease patients. We applied a retrospective cohort design on 29,095 elderly patients with end-stage renal disease who died between 2005 and 2013. These patients were identified from the National Health Insurance Research Database of Taiwan. The provider Continuity of Care Index (COCI) and site COCI were calculated on the basis of outpatient visits during the 6–12 months before death. We discovered that increases in the provider COCI were significantly associated with reductions in health expenditures after adjusting for confounders, especially in inpatient and emergency departments, where the treatment intensity is high. Higher provider and site COC were also associated with lower utilization of acute care and invasive treatments in the last month before death. Provider COC had a greater effect on end-of-life care expenditures than site COC did, which indicated significant care coordination gaps within the same facility. Our findings support the recommendation of prioritizing the continuity of end-of-life care, especially provider continuity, for patients with end-stage renal disease.

Few studies have explored the relationship between long-term exposure to particulate matter with an aerodynamic diameter of ≤2.5 μm (PM2.5) and osteoporotic fracture, particularly in high PM2.5 level areas. The aim of this study was to assess the association between long-term exposure to PM2.5 and osteoporotic fracture. We performed a matched case–control study of 16,175 participants obtained from a hospital registry during 2005–2014 in Taiwan. A major osteoporotic fracture was defined as a fracture of the spine, hip, proximal humerus, and forearm. We applied satellite-based spatiotemporal models with 1-km resolution to individually calculate the 1-year average PM2.5 concentration before the index date which was defined as the first visit date for the osteoporotic fracture. Logistic regression models with and without potential confounding factors were used to estimate odds ratios (OR) and 95% confidence intervals (CI) between PM2.5 and osteoporotic fracture, whereas a restricted cubic spline model was used to estimate the dose–response relationship. The sample's median age was 44.7 years (interquartile range: 30.7, 63.1 years). We observed that long-term PM2.5 exposure was associated with osteoporotic fracture, the OR was 1.12 (95% CI: 1.03, 1.22) per 10-μg/m3 increase in PM2.5 in women. In the dose-response association, the OR of osteoporotic fracture was significantly increased for PM2.5 exposures more than 41 μg/m3. We did not find a significant association between PM2.5 (per 10-μg/m3 increase) and osteoporotic fracture among overall population (adjusted OR, 1.02 [95% CI, 0.97 to 1.08]) and men (adjusted OR, 0.94 [95% CI, 0.86 to 1.02]). The results of the stratified analysis showed that women were more sensitive to the adverse impact of PM2.5 that were men, and evidence was obtained of sex-based effect modification (P for interaction = 0.002). Our findings suggest that long-term exposure to PM2.5 is associated with osteoporotic fracture, particularly among women.

Background Primary aldosteronism ( PA ) is associated with higher atrial fibrillation prevalence and other cardiovascular complications. However, the effect of target treatment to prevent new‐onset atrial fibrillation ( NOAF ) remains unclear. This study investigated incidence of NOAF under different treatment strategies in patients with PA. Methods and Results We analyzed longitudinal data for patients with PA without atrial fibrillation history from 1997 to 2009 within the National Health Insurance Research Database in Taiwan. Patients with essential hypertension matched by propensity score were enrolled as controls. The primary outcome measurement was NOAF , and secondary outcome measurements were mortality, major cardiac and cardiac/cerebrovascular events, and a combined end point of NOAF and mortality. We identified 2202 patients with PA (534 adrenalectomy, 1668 mineralocorticoid receptor antagonist [MRA] therapy) and 8808 essential hypertension controls with mean follow‐up of 4.4 years. In primary outcome measurement, patients with PA who underwent adrenalectomy had a lower incidence of NOAF (adjusted hazard ratio; 0.28, P =0.011) than controls. In contrast, the patients with PA who received MRA therapy had comparable risk of NOAF (adjusted hazard ratio, 1.20; P =0.224). In secondary outcome measurement, patients with PA who underwent adrenalectomy had a lower rate of mortality and combined end point of NOAF and mortality than controls. Patients with PA who received MRA therapy had a higher risk of mortality, major cardiac and cardiac/cerebrovascular events, and combined NOAF with mortality than the essential hypertension controls. Conclusions Compared with patients with essential hypertension, patients with PA who underwent adrenalectomy had a lower incidence of NOAF . However, this finding was not observed in patients with PA who received MRA therapy with a lower dose. Differences between the 2 strategies may reduce with a higher dose of MRA therapy.

Background Scarce evidence associates the first-year estimated glomerular filtration rate (eGFR) variability and longitudinal change scales concomitantly to the risk of developing end-stage renal disease (ESRD), acute coronary syndrome (ACS) and death following pre-ESRD program enrollment in chronic kidney disease (CKD). Methods We conducted a prospective cohort study of 5092 CKD patients receiving multidisciplinary care between 2003 and 2015 with careful ascertainment of ESRD, ACS and death during the follow-up. First-year eGFR variability and longitudinal change scales that were based on all first-year eGFR measurements included coefficient of variation of eGFR (eGFR-CV), percent change (eGFR-PC), absolute difference (eGFR-AD), slope (eGFR-slope) and area under the curve (AUC). Results A total of 786 incident ESRD, 292 ACS and 410 death events occurred during the follow-up. In the multiple Cox regression, the fully adjusted hazard ratios (HRs) of progression to ESRD for each unit change in eGFR-CV, eGFR-PC, eGFR-AD, eGFR-slope, eGFR-AUC were 1.03 [95% confidence interval (CI) 1.02–1.04], 1.04 (1.03–1.04), 1.16 (1.14–1.18), 1.16 (1.14–1.17) and 1.04 (1.03–1.04), respectively. The adjusted HRs for incident ESRD comparing the extreme with the reference quartiles of eGFR-CV, eGFR-PC, eGFR-AD, eGFR-slope and eGFR-AUC were 2.67 (95% CI 2.11–3.38), 8.34 (6.33–10.98), 19.08 (11.89–30.62), 13.08 (8.32–20.55) and 6.35 (4.96–8.13), respectively. Similar direction of the effects on the risk of developing ACS and mortality was observed. In the 2 × 2 risk matrices, patients with the highest quartile of eGFR-CV and concomitantly with the most severely declining quartiles of any other longitudinal eGFR change scale had the highest risk of all outcomes. Conclusions The dynamics of eGFR changes, both overall variability and longitudinal changes, over the first year following pre-ESRD program enrollment are crucial prognostic factors for the risk of progression to ESRD, ACS and deaths among patients with CKD. A risk matrix combining the first-year eGFR variability and longitudinal change scales following pre-ESRD enrollment is a novel approach for risk characterization in CKD care. Randomized trials in CKD may be required to ascertain comparable baseline eGFR dynamics.

Current acute kidney injury (AKI) diagnostic criteria are restricted to the inpatient setting. We proposed a new AKI diagnostic algorithm for the outpatient setting and evaluate whether outpatient AKI (AKIOPT) modifies the disease course among patients with chronic kidney disease (CKD) enrolled in the national predialysis registry. AKIOPT was detected when a 50% increase in serum creatinine level or 35% decline in eGFR was observed in the 180-day period prior to enrollment in the predialysis care program. Outcomes were progression to end-stage renal disease (ESRD) and all-cause mortality. Association analyses were performed using multiple Cox regression and coarsened exact matching (CEM) analysis. Among 6,046 patients, 31.5% (1,905 patients) had developed AKIOPT within the 180-day period before enrollment. The adjusted hazard ratios of the 1-year and overall risk of ESRD among patients with preceding AKIOPT compared with those without AKIOPT were 2.61 (95% CI: 2.15–3.18) and 1.97 (1.72–2.26), respectively. For 1-year and overall risk of all-cause mortality, patients with AKIOPT had respectively a 141% (95% CI: 89–209%) and 84% (56–117%) higher risk than those without AKIOPT. This statistical inference remained robust in CEM analysis. We also discovered a complete reversal in the eGFR slope before and after the AKIOPT from −10.61 ± 0.32 to 0.25 ± 0.30 mL/min/1.73 m2 per year; however, the loss of kidney function is not recovered. The new AKIOPT diagnostic algorithm provides prognostic insight in patients with CKD.

Background Current guidelines have unsatisfied performance in predicting severe outcomes after Clostridium difficile infection (CDI). Our objectives were to develop a risk prediction model for 30-day mortality and to examine its performance among inpatients with CDI. Methods This retrospective cohort study was conducted at China Medical University Hospital, a 2111-bed tertiary medical center in central Taiwan. We included adult inpatients who had a first positive C. difficile culture or toxin assay and had diarrhea as the study population. The main exposure of interest was the biochemical profiles of white blood cell count, serum creatinine (SCr), estimated glomerular filtration rate, blood urea nitrogen (BUN), serum albumin, and glucose. The primary outcome was the 30-day all-cause mortality and the secondary outcome was the length of stay in the intensive care units (ICU) following CDI. A multivariable Cox model and a logistic regression model were developed using clinically relevant and statistically significant variables for 30-day mortality and for length of ICU stay, respectively. A risk scoring system was established by standardizing the coefficients. We compared the performance of our models and the guidelines. Results Of 401 patients, 23.4% died within 30 days. In the multivariable model, malignancy (hazard ratio [HR] = 1.95), ≥ 1.5-fold rise in SCr (HR = 2.27), BUN-to-SCr ratio > 20 (HR = 2.04), and increased glucose (≥ 193 vs 20 (Odds ratio [OR] = 4.01) was the only significant predictor for prolonged (> 9 days) length of ICU stay following CDI. The Harrell’s c statistic of our Cox model for 30-day mortality (0.727) was significantly superior to those of SHEA-IDSA 2010 (0.645), SHEA-IDSA 2018 (0.591), and ECSMID (0.650). Similarly, the conventional c statistic of our logistic regression model for prolonged ICU stay (0.737) was significantly superior to that of the guidelines (SHEA-IDSA 2010, c = 0.600; SHEA-IDSA 2018, c = 0.634; ESCMID, c = 0.645). Our risk prediction scoring system for 30-day mortality correctly reclassified 20.7, 32.1, and 47.9% of patients, respectively. Conclusions Our model that included novel biomarkers of BUN-to-SCr ratio and glucose have a higher predictive performance of 30-day mortality and prolonged ICU stay following CDI than do the guidelines.

Rationale & Objective Limited evidence concerns fine particulate matter (with aerodynamic diameter ≤ 2.5μm [PM2.5]) exposure and the risk for kidney failure with replacement therapy (KFRT). This study assessed whether PM2.5 exposure was associated with progression of chronic kidney disease (CKD) to KFRT. Study Design Prospective cohort study. Setting & Participants 6,628 adult patients with CKD were recruited from the Advanced CKD Program in Taiwan between 2003 and 2015. Exposure Satellite-based spatiotemporal models were used to calculate each individual's 1-year PM2.5 exposure before the date of enrollment into the Advanced CKD Program. Outcomes Time to KFRT (defined as initiation of maintenance hemodialysis, peritoneal dialysis, or kidney transplantation) and time to all-cause mortality. Analytical Approach Multivariable proportional hazard regression analyses were used to estimate the association of PM2.5 with KFRT and all-cause mortality. Restricted cubic splines were used to explore dose-response relationships. Results The study population included 6,628 adult patients with CKD who were aged 20 to 90 years. 941 KFRT events and 1,653 deaths occurred during follow-up. The adjusted HR for progression to KFRT was 1.19 (95% CI, 1.08-1.31) per 7.8μg/m3 greater PM2.5, an amount spanning the interquartile range. There was evidence of a dose-response relationship (adjusted HRs of 1.16 [95% CI, 0.90-1.51], 1.19 [95% CI, 0.94-1.52], and 1.42 [95% CI, 1.12-1.80] for low, medium, and high PM2.5 levels). There was no significant association between PM2.5 and all-cause mortality (adjusted HR, 1.01 [95% CI, 0.95-1.08]). Limitations Misclassification of PM2.5 exposure assessment and the potential for residual confounding. Conclusions Our findings suggest that long-term exposure to PM2.5 is associated with increased risk for progression to KFRT in patients with CKD.

At high levels, inorganic arsenic exposure is linked to peripheral arterial disease (PAD) and cardiovascular disease. To our knowledge, no prior study has evaluated the association between low-to-moderate arsenic exposure and incident PAD by ankle brachial index (ABI). We evaluated this relationship in the Strong Heart Study, a large population-based cohort study of American Indian communities. A total of 2,977 and 2,966 PAD-free participants who were aged 45–74 years in 1989–1991 were reexamined in 1993–1995 and 1997–1999, respectively, for incident PAD defined as either ABI 1.4. A total of 286 and 206 incident PAD cases were identified for ABI 1.4, respectively. The sum of inorganic and methylated urinary arsenic species (∑As) at baseline was used as a biomarker of long-term exposure. Comparing the highest tertile of ∑As with the lowest, the adjusted hazard ratios were 0.57 (95% confidence interval (CI): 0.32, 1.01) for ABI 1.4. Increased arsenic methylation (as percent dimethylarsinate) was associated with a 2-fold increased risk of ABI >1.4 (hazard ratio = 2.04, 95% CI: 1.02, 3.41). Long-term low-to-moderate ∑As and increased arsenic methylation were associated with ABI >1.4 but not with ABI

OBJECTIVE Little is known about arsenic and diabetes in youth. We examined the association of arsenic with type 1 and type 2 diabetes in the SEARCH for Diabetes in Youth Case-Control (SEARCH-CC) study. Because one-carbon metabolism can influence arsenic metabolism, we also evaluated the potential interaction of folate and vitamin B12 with arsenic metabolism on the odds of diabetes. RESEARCH DESIGN AND METHODS Six hundred eighty-eight participants RESULTS Median ∑As, iAs%, MMA%, and DMA% were 83.1 ng/L, 63.4%, 10.3%, and 25.2%, respectively. ∑As was not associated with either type of diabetes. The fully adjusted odds ratios (95% CI), rescaled to compare a difference in levels corresponding to the interquartile range of iAs%, MMA%, and DMA%, were 0.68 (0.50–0.91), 1.33 (1.02–1.74), and 1.28 (1.01–1.63), respectively, for type 1 diabetes and 0.82 (0.48–1.39), 1.09 (0.65–1.82), and 1.17 (0.77–1.77), respectively, for type 2 diabetes. In interaction analysis, the odds ratio of type 1 diabetes by MMA% was 1.80 (1.25–2.58) and 0.98 (0.70–1.38) for participants with plasma folate levels above and below the median (P for interaction = 0.02), respectively. CONCLUSIONS Low iAs% versus high MMA% and DMA% was associated with a higher odds of type 1 diabetes, with a potential interaction by folate levels. These data support further research on the role of arsenic metabolism in type 1 diabetes, including the interplay with one-carbon metabolism biomarkers.

Background: The link among perfluoroalkyl and polyfluoroalkyl substances (PFASs), abnormal glucose homeostasis and the risk of diabetes has been intensively debated with conflicting evidence. Objectives: We evaluated the associations among PFASs, oral glucose tolerance testing (OGTT) curves and diabetes prevalence in 571 working-aged Taiwanese participants. Methods: Exposure measures included serum perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA). Outcomes were OGTT curves and prevalent diabetes defined by fasting blood glucose (FBG) ≥126 mg/dL, 2-h glucose ≥200 mg/dL, or glycated hemoglobin ≥6.5%. Analyses were performed with multiple logistic regression and functional data analysis. Results: A total of 39 participants (6.8%) had diabetes in this study. After full adjustment, the increase in the geometric means of FBG, 2-h glucose concentrations, and area under the OGTT curve (AUC120) with a doubling increase in PFOS was 3% (95% CI 1–4), 8% (5–12), and 6% (4–9), respectively. Compared to the lowest-quartile of PFOS concentrations (4.8 ng/ml) and the vertical shifting of the mean curve for each PFOS quartile showed a dose–response pattern. The adjusted odds ratio for diabetes comparing the highest to lowest quartile was 3.37 (95% CI 1.18–9.65). For PFOA, PFNA, and PFUA, the opposite pattern of OGTT trajectory and the opposite risk profile for diabetes were observed. Conclusions: Chronic PFOS exposure was associated with impaired glucose homeostasis and the increased prevalence of diabetes. However, PFOA, PFNA, and PFUA showed a potential protective effect against glucose intolerance and the risk of diabetes. Future research focusing on clarifying possible differential effects of different species of PFASs on glucose homeostasis and establishing the prospective associations between PFASs and diabetes is needed. Keywords: Perfluorinated chemicals, Oral glucose tolerance testing, Diabetes, Glucose homeostasis

The optimal timing to initiate dialysis among patients with an estimated glomerular filtration rate (eGFR) of

Background Prognostic role of red blood cell distribution width (RDW) in patients with chronic kidney disease (CKD) is unclear. Little evidence provides a comprehensive predictive analysis considering both baseline values and longitudinal trajectories of RDW along with mean corpuscular volume (MCV). Methods We conducted a comprehensive risk assessment of RDW and MCV in a registry-based cohort of 4621 patients with CKD (age, 20–90 y) receiving multidisciplinary care during 2003 to 2015. Both baseline and longitudinal trajectories of RDW and MCV were modeled as predictors for end-stage renal disease (ESRD) and mortality by using multiple Cox proportional hazards regression models, incorporating time-varying covariates and adjustments for imperative confounding variables. Results Fully adjusted hazard ratio (HR; 95% CI) of progression to ESRD for each unit increase in RDW and MCV at baseline was 0.97 (0.93–1.02) and 1.00 (0.99–1.01), respectively. Longitudinally, neither RDW nor MCV trajectory was associated with progression to ESRD. For all-cause mortality, fully adjusted HRs (95%CI) were 1.09 (1.04–1.14) for each percent increase in RDW with a linear dose–response relationship and 1.95 (1.47–2.59) for a stable-high RDW trajectory compared with normal RDW trajectory. The effects of RDW on mortality were further augmented in patients with concomitantly high MCV status. Incorporating point-of-care RDW significantly improves the discrimination performance quantified using Harrell C statistics into the existing CKD mortality predictive equation (from 0.770 to 0.784, P = .018). Conclusions We support the clinical utility of RDW in predicting all-cause mortality among patients with CKD. The mechanism underlying our findings is critical for CKD risk assessment and management, particularly from malnutrition, inflammation, and atherosclerosis perspectives.

Background The trajectory pattern of erythrocyte sedimentation rate (ESR) in patients with pyogenic vertebral osteomyelitis (PVO) and its clinical significance is unclear. We further evaluated whether the first-4-week ESR variability can predict the trajectory pattern, treatment duration and recurrence of PVO. Methods The longitudinal ESR patterns of adults with PVO within the first 6 months were characterized through group-based trajectory modeling (GBTM). The ESR variability within the first 4 weeks was defined using the absolute difference (AD), coefficient of variation, percent change, and slope change. The first-4-week ESR variabilities were analyzed using ordinal logistic regression to predict the 6-month ESR trajectory and using logistic regression to predict treatment duration and recurrence likelihood. The discrimination and calibration of the prediction models were evaluated. Results Three ESR trajectory patterns were identified though GBTM among patients with PVO: Group 1, initial moderate high ESR with fast response; Group 2, initial high ESR with fast response; Group 3, initial high ESR with slow response. Group 3 patients (initial high ESR with slow response) were older, received longer antibiotic treatment, and had more comorbidities and higher recurrence rates than patients in the other two groups. The initial ESR value and ESR − AD could predict the 6-month ESR trajectory. By incorporating the first-4-week ESR variabilities and the clinical features of patients, our models exhibited moderate discrimination performance to predict prolonged treatment (≥12 weeks; C statistic, 0.75; 95% confidence interval [CI], 0.70 to 0.81) and recurrence (C statistic, 0.69; 95% CI, 0.61 to 0.78). Conclusions The initial ESR value and first-4-week ESR variability are useful markers to predict the treatment duration and recurrence of PVO. Future studies should validate our findings in other populations.

Background: The global prevalence of type 2 diabetes continues to increase in both developed and developing countries. Environmental exposure to mercury may be an important and modifiable risk factor for type 2 diabetes. However, the epidemiological results are controversial. Objectives: This study aimed to examine the association between blood mercury levels and prevalence of type 2 diabetes. Methods: A total of 646 adult participants were selected from the National Nutrition and Health Survey in Taiwan (NAHSIT) 2005–2008. The participants were interviewed using structured questionnaires to record data on basic demographics, socioeconomic status, lifestyle, medical history, and 24-h dietary recall. Specimens of blood and urine were collected at the health examination. Type 2 diabetes was defined as a fasting blood glucose level ≥ 126 mg/dL or intake of hypoglycemic medications. The mercury concentration in red blood cells (RBC-Hg) was quantified by cold vapor atomic absorption spectrometry. Results: Participants with type 2 diabetes had a significantly higher RBC-Hg than those without type 2 diabetes. A significant association between the RBC-Hg and prevalence of type 2 diabetes was observed [odds ratio (OR): 1.64; 95% confidence intervals: 1.14–2.35] after potential confounders were well considered, including age, sex, body mass index (BMI), hypertension, total cholesterol, saltwater fish consumption, geographical strata, seasonality and hemoglobin (Hb) level. Conclusion: Our findings showed that elevated RBC-Hg is significantly associated with type 2 diabetes prevalence. Future research, particularly for longitudinal cohort studies with suitable specimens, needs to be performed to verify our findings. Keywords: Type 2 diabetes, Mercury exposure, Methylmercury, National Nutrition and Health Survey in Taiwan

Background: Costs of medical care have been found to be highest at the end of life. Aim: To evaluate the effect of provider reimbursement for hospice care on end-of-life costs. Design: The policy expanded access to hospice care for end-stage renal disease patients, a policy previously limited to cancer patients only. This study employed a difference-in-differences analysis using a generalized linear model. The main outcome is inpatient expenditures in the last 30 days of life. Setting/participants: A cohort of 151,509 patients with chronic kidney disease or cancer, aged 65 years or older, who died between 2005 and 2012 in the National Health Insurance Research Database, which contains all enrollment and inpatient claims data for Taiwan. Results: Even as end-of-life costs for cancer are declining over time, expanding hospice care benefits to end-stage renal disease patients is associated with an additional reduction of 7.3% in end-of-life costs per decedent, holding constant patient and provider characteristics. On average, end-of-life costs are also high for end-stage renal disease (1.88 times higher than those for cancer). The cost savings were larger among older patients—among those who died at 80 years of age or higher, the cost reduction was 9.8%. Conclusion: By expanding hospice care benefits through a provider reimbursement policy, significant costs at the end of life were saved.

Background: There is very limited information on the association between arsenic and serum uric acid levels or gout. The aim of this study was to investigate the association of arsenic with hyperuricemia and gout in US adults. Methods: A cross-sectional study was conducted in 5632 adults aged 20 years or older from the National Health and Nutrition Examination Survey (NHANES) 2003–2010 with determinations of serum uric acid and urine total arsenic and dimethylarsinate (DMA). Hyperuricemia was defined as serum uric acid higher than 7.0 mg/dL for men and 6.0 mg/dL for women. Gout was defined based on self-reported physician diagnosis and medication use. Results: After adjustment for sociodemographic factors, comorbidities and arsenobetaine levels, the increase in the geometric means of serum uric acid associated with one interquartile range increase in total arsenic and DMA levels was 3% (95% CI 2–5) and 3% (2–5), respectively, in men and 1% (0–3) and 2% (0–4), respectively, in women. In men, the adjusted odds ratio for hyperuricemia comparing the highest to lowest quartiles of total arsenic was 1.84 (95% CI, 1.26–2.68) and for DMA it was 1.41 (95% CI, 1.01–1.96). The corresponding odds ratios in women were 1.26 (0.77, 2.07) and 1.49 (0.96, 2.31), respectively. The odds ratio for gout comparing the highest to lowest tertiles was 5.46 (95% CI, 1.70–17.6) for total arsenic and 1.98 (0.64–6.15) for DMA among women older than 40 years old. Urine arsenic was not associated with gout in men. Conclusion: Low level arsenic exposures may be associated with the risk of hyperuricemia in men and with the prevalence of gout in women. Prospective research focusing on establishing the direction of the relationship among arsenic, hyperuricemia, and gout is needed. Keywords: Uric acid, Hyperuricemia, Arsenic, Lead, Gout

OBJECTIVE Little is known about arsenic metabolism in diabetes development. We investigated the prospective associations of low-moderate arsenic exposure and arsenic metabolism with diabetes incidence in the Strong Heart Study. RESEARCH DESIGN AND METHODS A total of 1,694 diabetes-free participants aged 45–75 years were recruited in 1989–1991 and followed through 1998–1999. We used the proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) over their sum (expressed as iAs%, MMA%, and DMA%) as the biomarkers of arsenic metabolism. Diabetes was defined as fasting glucose ≥126 mg/dL, 2-h glucose ≥200 mg/dL, self-reported diabetes history, or self-reported use of antidiabetic medications. RESULTS Over 11,263.2 person-years of follow-up, 396 participants developed diabetes. Using the leave-one-out approach to model the dynamics of arsenic metabolism, we found that lower MMA% was associated with higher diabetes incidence. The hazard ratios (95% CI) of diabetes incidence for a 5% increase in MMA% were 0.77 (0.63–0.93) and 0.82 (0.73–0.92) when iAs% and DMA%, respectively, were left out of the model. DMA% was associated with higher diabetes incidence only when MMA% decreased (left out of the model) but not when iAs% decreased. iAs% was also associated with higher diabetes incidence when MMA% decreased. The association between MMA% and diabetes incidence was similar by age, sex, study site, obesity, and urine iAs concentrations. CONCLUSIONS Arsenic metabolism, particularly lower MMA%, was prospectively associated with increased incidence of diabetes. Research is needed to evaluate whether arsenic metabolism is related to diabetes incidence per se or through its close connections with one-carbon metabolism.

High arsenic exposure has been related to diabetes, but at low-moderate levels the evidence is mixed. Arsenic metabolism, which is partly genetically controlled and may rely on certain B vitamins, plays a role in arsenic toxicity.We evaluated the prospective association of arsenic exposure and metabolism with type 2 diabetes and insulin resistance.We included 1,838 American Indian men and women free of diabetes (median age, 36 y). Arsenic exposure was assessed as the sum of inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) urine concentrations (ΣAs). Arsenic metabolism was evaluated by the proportions of iAs, MMA, and DMA over their sum (iAs%, MMA%, and DMA%). Homeostasis model assessment for insulin resistance (HOMA2-IR) was measured at baseline and follow-up visits. Incident diabetes was evaluated at follow-up.Median ΣAs, iAs%, MMA%, and DMA% was 4.4 μg/g creatinine, 9.5%, 14.4%, and 75.6%, respectively. Over 10,327 person-years of follow-up, 252 participants developed diabetes. Median HOMA2-IR at baseline was 1.5. The fully adjusted hazard ratio [95% confidence interval (CI)] for incident diabetes per an interquartile range increase in ΣAs was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. ΣAs was positively associated with HOMA2-IR at baseline but negatively with HOMA2-IR at follow-up. Increased MMA% was associated with lower HOMA2-IR when either iAs% or DMA% decreased. The association of arsenic metabolism with HOMA2-IR differed by B-vitamin intake andAmong participants without baseline prediabetes, arsenic exposure was associated with incident diabetes. Low MMA% was cross-sectional and prospectively associated with higher HOMA2-IR. Research is needed to confirm possible interactions of arsenic metabolism with B vitamins and

Background Direct comparisons of the effectiveness of allopurinol with that of other urate-lowering agents in chronic kidney disease (CKD) populations, as well as guideline recommendations for clinical practice, are lacking. Methods We constructed a pharmacoepidemiology cohort study by including patients from Taiwan's long-term integrated CKD care program to compare the effectiveness among allopurinol, febuxostat and benzbromarone in reducing the risk of progression to dialysis. A total of 874 patients with hyperuricemia who were newly treated with allopurinol, febuxostat or benzbromarone were included. The primary and secondary outcomes were incident end-stage renal disease (ESRD) and the serum uric acid (SUA) changes from baseline, respectively. The results were analyzed using multiple Cox proportional models adjusted for multinomial propensity scores. For subgroup analyses, we further stratified patients according to whether their latest SUA level reached the therapeutic target. Results Compared with allopurinol, benzbromarone therapy was associated with a reduced risk of progression to dialysis, the adjusted hazard ratio was 0.50 (95% confidence interval, 0.25-0.99). Patients who received allopurinol or febuxostat exhibited a comparable risk of ESRD [adjusted hazard ratio, 0.99 (0.40-2.44)]. Febuxostat was significantly more potent than allopurinol or benzbromarone in lowering SUA levels in the fully adjusted model. Among patients who reached the therapeutic target, those with febuxostat and benzbromarone initiation had a significantly lower risk of ESRD. Conclusions In conclusion, compared with conventional allopurinol, febuxostat and benzbromarone may be more effective in reducing the risk of progression to dialysis and in lowering SUA levels in CKD populations.

Background The clinical importance of random urine creatinine concentration in CKD population remains undetermined. Earlier studies found that lower 24-h urine creatinine excretion was associated with the risk of ESRD and all-cause mortality among CKD patients. Methods We modeled the longitudinal trajectories of serial random urine creatinine among 4689 CKD patients enrolled in a national registry-based pre-ESRD program between 2003 and 2015 at a tertiary medical center. Other biochemical parameters including kidney function and serum albumin were regularly evaluated. Primary study outcomes were ESRD requiring maintenance dialysis and all-cause mortality. Results By group-based trajectory modeling, the urine creatinine trajectories were characterized into three patterns: (1) stable low; (2) medium; and (3) high-declining. The adjusted hazard ratio of incident ESRD and all-cause mortality increased by 6% (95% CI: 1–12%) and 9% (95% CI: 2–17%), respectively, for each 20 mg/dL reduction in baseline random urine creatinine concentration. Consistently, there was a significant inverse linear dose-response relationship between baseline random urine creatinine and incident ESRD, but not all-cause mortality. Compared to patients with “medium” and “high-declining” urine creatinine trajectories combined, the adjusted hazard ratio for incidental ESRD among patients with a “stable-low” trajectory who had serial random urine creatinine concentrations stably below 100 mg/dL was 1.46 (95% CI: 1.00–2.12) after considering the competing risk of death. Conclusions Random urine creatinine not only serves as a common urinary concentration corrector but has its own clinical significance in risk stratification and outcome prediction in patients with advanced CKD.

Background Very little is known about longitudinal trajectories of serum uric acid (SUA) over the course of chronic kidney disease (CKD). We aimed to determine whether longitudinal SUA trajectories are associated with the risk of end-stage renal disease (ESRD) and all-cause mortality among CKD patients. Methods We conducted a prospective cohort study from a 13-year multidisciplinary pre-ESRD care registry. The final study population consisted of 5090 CKD patients aged 20-90 years between 2003 and 2015. An individual's SUA trajectory was defined by group-based trajectory modeling in four distinct patterns: high, moderate-high, moderate and low. Time to ESRD and death was analyzed by multiple Cox regression. Results A total of 948 ESRD events and 472 deaths occurred with incidence rates of 57.9 and 28.7 per 1000 person-years, respectively. Compared with those with a low SUA trajectory, the adjusted hazard ratio of patients for incident ESRD was in a dose-response manner as follows: moderate, 1.89 [95% confidence interval (CI), 1.37-2.60]; moderate-high, 2.49 (1.75-3.55); and high, 2.84 (1.81-4.47); after considering the competing risk of death. For all-cause mortality, the corresponding risk estimate of the same SUA trajectory was 1.38 (95% CI, 0.89-2.12), 1.95 (1.22-3.10) and 4.52 (2.48-8.26), respectively. The unfavorable effect of elevated SUA trajectories on progression to ESRD was differentially higher among CKD patients without using urate-lowering agents at baseline (P for interaction = 0.018). Conclusions Elevated SUA trajectories are associated with accelerated kidney failure and all-cause mortality in CKD patients. Adequate experimental evidence is urgently needed to inform when and how to optimize SUA in this population.

B-vitamins involved in one-carbon metabolism (OCM) can affect arsenic metabolism efficiency in highly arsenic exposed, undernourished populations. We evaluated whether dietary intake of OCM nutrients (including vitamins B2, B6, folate (B9), and B12) was associated with arsenic metabolism in a more nourished population exposed to lower arsenic than previously studied. Dietary intake of OCM nutrients and urine arsenic was evaluated in 405 participants from the Strong Heart Study. Arsenic exposure was measured as the sum of iAs, monomethylarsonate (MMA) and dimethylarsenate (DMA) in urine. Arsenic metabolism was measured as the individual percentages of each metabolite over their sum (iAs%, MMA%, DMA%). In adjusted models, increasing intake of vitamins B2 and B6 was associated with modest but significant decreases in iAs% and MMA% and increases in DMA%. A significant interaction was found between high folate and B6 with enhanced arsenic metabolism efficiency. Our findings suggest OCM nutrients may influence arsenic metabolism in populations with moderate arsenic exposure. Stronger and independent associations were observed with B2 and B6, vitamins previously understudied in relation to arsenic. Research is needed to evaluate whether targeting B-vitamin intake can serve as a strategy for the prevention of arsenic-related health effects at low-moderate arsenic exposure.

The ever-increasing global epidemic of type 2 diabetes has overwhelmed the capacity of healthcare systems and economies in both developing and developed countries.1 Economic development, rapid industrialization and social re-organization may play a critical role in driving the diabetes epidemic, possibly due to discordant gene-environment interactions.1,2 The evolution discordance induced by rapid environment modifications is most acknowledged in nutrition transition to ubiquitous refined and processed foods, and in physical activity transition to sedentary lifestyle — especially screen watching and driving.1,2 Compared with diet and physical activity, the impact of environmental chemicals on diabetes development has been grossly under-researched and their effects possibly underestimated. By the end of the 20th century, however, growing epidemiological and mechanistic evidence had started to link environmental chemicals (both synthetic and naturally occurring) to type 2 diabetes and obesity.3,4 In 2011, the U.S. National Toxicological Program at the National Institute of Environmental Health Sciences in the USA organized a workshop to systematically review the epidemiological and experimental evidence on the relationship of environmental chemicals with obesity, diabetes and the metabolic syndrome for a wide variety of chemicals including metals (arsenic), persistent organic pollutants, phthalates, bisphenol A, non-persistent pesticides and air pollution.4 Although the evidence has been updated in recent reviews, it is far from establishing causality. A major limitation is that most available studies are cross-sectional, except for arsenic, hexachlorobenzene (HCB) and total polychlorinated biphenyls (PCBs) for which increasing prospective evidence is generally consistent with an increased risk of type 2 diabetes.3 Among toxic metals associated with the risk of diabetes, arsenic, a metalloid, has received special attention for more than two decades since the publication in 1994 of a cross-sectional study in the historically high-arsenic area of south-western Taiwan.5 The research focus has since then expanded from high to low-moderate arsenic exposures and from occupational populations to general populations, with increasing evidence supporting the diabetogenic effects of arsenic even at exposure levels below the World Health Organization standard of 10 ppb in drinking water. However, the debate on the causality of the observed associations between arsenic and diabetes remains unresolved, mainly because of limited quality assessment of arsenic and diabetes outcomes and still relatively limited prospective data.3,4 For other metals, the evidence is scarce. A handful of studies are available for mercury, with inconsistent evidence, and for cadmium, with evidence generally supporting no association.3 In this issue of the International Journal of Epidemiology, Liu et al. report a cross-sectional association between nickel exposure, as measured in urine, with the prevalence of diabetes in a representative sample of adults aged 50 to 70 years from two main cities in China, Beijing and Shanghai.6 This is the first study formally evaluating the hypothesis of an association between nickel exposure and the risk of diabetes, and the results could represent a novel finding. However, we must exert great caution in interpreting the findings of this single study, especially given important limitations, namely the cross-sectional design. Reverse causation is an inherent limitation in cross-sectional studies, especially when the exposure is based on urine analysis and the disease outcome is potentially associated with kidney injury ranging from glomerular hyperfiltration to impaired glomerular filtration. The possibility of reverse causality in the exposure-outcome relationship poses a serious challenge for researchers investigating the association between diabetes and urinary chemicals. For example, in Liu et al.’s study, it would be important to report the association between estimated glomerular filtration rate (eGFR) and urine nickel concentrations and whether the eGFR is comparable between participants with and without diabetes. This information, however, was not reported. In general, for diseases that could affect kidney function, prospective evidence is particularly important when exposure assessment is based on urine biomarkers. Another challenge is how to deal with multiple toxic metals, or by extension with multiple environmental chemicals, that are potentially diabetogenic. Liu et al. mentioned that urine arsenic and cadmium levels were adjusted for in sensitivity analyses yielding consistent results.6 However, effect modification by arsenic or cadmium exposure was not approached systematically, including the evaluation of additive or multiplicative effects. It would have been useful to report the association of arsenic and cadmium with prevalent diabetes in this population, since the information was available and given the need to assess multi-exposure. Residual confounding is an inherent threat to the validity of any observational study. For instance, higher nickel exposure may be attributable to higher particulate air pollution, which has also been linked to the development of diabetes, as nickel concentrations and particulate matter exposure can be correlated.7,8 Other sources of nickel exposure include electronic devices such as laptops and cellphones.9 Clarifying the main source of nickel exposure in the general population would be critical to control residual confounding and perform bias estimation. Unlike arsenic, where the evidence at high levels of exposure is generally consistent, no information is available on a link between nickel exposure and type 2 diabetes in occupational populations or in highly exposed general populations. Targeting prospective research studies in occupationally exposed populations in industries such as mining, alloy manufacturing and production of nickel-based batteries may be a practical and cost-effective approach. Overall, well-designed prospective studies are warranted to evaluate the joint effect between nickel and other nutrients and toxicants and its impact on the risk of diabetes. It is also fundamental to estimate the repeatability of urine nickel measurements collected over time to justify the use of single urine nickel measurements, as the half-life of nickel in urine is relatively short. As multi-element analytical methods have become standard in metal assessment, developing statistical methods to deal with multi-exposures is critical. With the publication of the study by Liu et al.,6 nickel appears as a potential new chemical that was missing in our list of environmental chemicals that may be related to diabetes. At this point, the limited evidence available is insufficient to evaluate this relationship. In one ecological study, nickel concentration in the air was associated with diabetes mortality.10 In two case-control studies, on the other hand, serum nickel levels were similar between participants with and without diabetes.11,12 The study by Liu et al., however, highlights the possibility that a number of diabetes-related environmental chemicals might have been overlooked. With hundreds of new chemicals released every year, and studies that tend to focus on the same chemicals, it is important to acknowledge that new approaches are needed that can identify a larger number of environmental chemicals simultaneously while appropriately preserving quality in exposure assessment and control of bias, in particular confounding. Identifying environmental hazards for chronic disease such as diabetes is an urgent need as modernization contributes to rapid changes in environmental exposures. Environmental chemicals could also challenge the dynamic interplay with genetic, nutritional and physical activity factors and alter public health risk to chronic diseases, especially in countries with rapid socio-economic growth and urbanization, such as China and India.1

Background Despite the urgent need for evidence to guide the end-of-life (EOL) care for patients with chronic kidney disease (CKD), we have limited knowledge of the costs and intensity of EOL care in this population. The present study examined patterns and predictors for EOL care intensity among elderly patients with CKD. Methods We conducted a retrospective nationwide cohort study utilizing the Taiwan National Health Insurance (NHI) Research Database. A total of 65,124 CKD patients aged ≥ 60 years, who died in hospitals or shortly after discharge between 2002 and 2012 were analyzed. The primary outcomes were inpatient expenses and use of surgical interventions in the last 30 days of life. Utilization of intensive care unit (ICU), mechanical ventilation, resuscitation, and dialysis was also examined in a sub-sample of 2072 patients with detailed prescription data. Multivariate log-linear and logistic regression analyses were performed to assess patient-, physician-, and facility-specific predictors and the potential impact of a 2009 payment policy to reimburse hospice care for non-cancer patients. Results During the last 30 days of life, average inpatients costs for elderly CKD patients were approximately US$10,260, with 40.9% receiving surgical interventions, 40.2% experiencing ICU admission, 45.3% undergoing mechanical ventilation, 14.7% receiving resuscitation and 42.0% receiving dialysis. Significant variability was observed in the inpatient costs and use of intensive services. Costs were lower among individuals with the following characteristics: advanced age; high income; high Charlson Comorbidity Index scores; treatment by older physicians, nephrologists, and family medicine physicians; and treatment at local hospitals. Similar findings were obtained for the use of surgical interventions and other intensive services. A declining trend was detected in the costs of EOL care, use of surgical interventions and resuscitation between 2009 and 2012, which is consistent with the impact of a 2009 NHI payment policy to reimburse non-cancer hospice care. Conclusions Overall EOL costs and rates of intensive service use among older patients with CKD were high, with significant variability across various patient and provider characteristics. Several opportunities exist for providers and policy makers to reduce costs and enhance the value of EOL care for this population.

Environmental factors contribute significantly to the pathogenesis of chronic kidney disease. However, these factors, and particularly the toxic effects of heavy metals, have not been completely evaluated. Chromium is a widespread industrial contaminant that has been linked to nephrotoxicity in animal and occupational population studies. Nevertheless, its role in population renal health and its potential interactions with other nephrotoxic metals, such as lead and cadmium, remain unknown. We assessed the association between exposure to chromium, lead, and cadmium with renal function using estimated glomerular filtration rate (eGFR) in an analysis of 360 Taiwanese adults aged 19–84 years from the National Nutrition and Health Survey in Taiwan (2005–2008). Doubling of urinary chromium or lead decreased the eGFR by -5.99 mL/min/1.73 m 2 (95% confidence interval -9.70, -2.27) and -6.61 (-9.71, -3.51), respectively, after adjusting for age, sex, body mass index, hypertension, diabetes, cigarette smoking, sodium intake, education, urinary volume, and other metals. For those in the highest tertile of cadmium exposure, the eGFR decreased by -12.68 mL/min/1.73 m 2 (95% confidence interval -20.44, -4.93) and -11.22 mL/min/1.73 m 2 (-17.01, -5.44), as urinary chromium or lead levels doubled, respectively. Thus, there is a significant and independent association between chromium exposure and decreased renal function. Furthermore, co-exposure to chromium with lead and cadmium is potentially associated with additional decline in the glomerular filtration rate in Taiwanese adults.

OBJECTIVES: To obtain information about the effect of prolonged aldosterone excess on kidney function. METHODS: We determined kidney function changes defined by cystatin C-based estimations of glomerular filtration rate (CysC-GFR). Pretreatment proteinuria and intrarenal Doppler velocimetric indices in primary aldosteronism were examined and followed after adrenalectomy or spironolactone treatment. RESULTS: This prospective, multicenter study included 130 primary aldosteronism patients (56 men; age, 49.9 ± 13.4 years: 100 with adenoma and 30 with idiopathic hyperaldosteronism) and 73 essential hypertension patients (36 men; age, 51.4 ± 14.8 years) as controls. Patients with primary aldosteronism had higher CysC-GFR (P < 0.05) and heavier proteinuria (0.042) than those with essential hypertension. With primary aldosteronism, a higher aldosterone-renin ratio (odds ratio, OR = 7.85, P = 0.008) was independently related to pretreatment CysC-GFR. The factors related to pretreatment proteinuria included CysC-GFR (OR, -0.006, P = 0.001), plasma aldosterone concentration (OR, 0.004, P = 0.002), and duration of hypertension (OR, 0.016, P = 0.032). Duration of hypertension was also independently correlated with the pretreatment resistive index among primary aldosteronism patients (OR, 0.004, P = 0.035). CysC-GFR (all, P < 0.05), proteinuria (P < 0.001), and resistive index (P < 0.001) decreased 1 year after adrenalectomy but not with spironolactone treatment. CONCLUSION: Our data suggest that prolonged hyperaldosteronism will cause relative kidney hyperfiltration and reversible intrarenal vascular structural changes, which disguise the consequent renal injury, including declining GFR and proteinuria. Adrenalectomy and spironolactone treatment exert different clinical impacts toward kidney damage even with a similar blood pressure-lowering effect.

Background Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with more prominent left ventricular hypertrophy and increased myocardial fibrosis. Unilateral hyperaldosteronism can be cured by adrenalectomy. However, the reversibility of cardiac fibrosis is still unclear. Methods We analyzed 11 patients prospectively with unilateral hyperaldosteronism (including 10 aldosterone-producing adenomas and 1 unilateral nodular hyperplasia) who received adrenalectomy from October 2006 to October 2007, and 17 patients with essential hypertension (EH) were enrolled as the control group. Echocardiography included ultrasonic tissue characterization by cyclic variation of integrated backscatter; it was performed in both groups and 1 year after operation in the unilateral hyperaldosteronism group. Results Patients with unilateral hyperaldosteronism had significantly higher diastolic blood pressure, higher plasma aldosterone concentration, lower serum potassium level, and lower plasma renin activity than patients with EH. In echocardiography, patients with unilateral hyperaldosteronism had thicker interventricular septal thickness, left ventricular posterior wall thickness, and higher left ventricular mass index than EH patients. Patients with unilateral hyperaldosteronism had significant lower cyclic variation of integrated backscatter than EH patients (7.1 ± 2.1 vs 8.7 ± 1.5 dB, P = .037). After analyzing the correlation of cyclic variation of integrated backscatter with clinical parameters for all participants, only log-transformed plasma renin activity was correlated significantly with cyclic variation of integrated backscatter. One year after adrenalectomy, interventricular septal thickness, left ventricular posterior wall thickness, and left ventricular mass index decreased significantly. In addition, cyclic variation of integrated backscatter increased significantly after adrenalectomy (7.1 ± 2.1 to 8.5 ± 1.5 dB, P = .02). Conclusion Adrenalectomy not only reversed left ventricular geometry but also altered myocardial texture in patients with unilateral hyperaldosteronism. This finding implies that increases in collagen content in the myocardium of patients with unilateral hyperaldosteronism might be reversed by adrenalectomy.

Background Though aldosterone–renin ratio (ARR) is the current routine screening method for suspicious primary aldosteronism, we hypothesized that the simple formula combining body mass index (BMI) and serum potassium to urine potassium clearance (PUKC) ratio was comparable to ARR. Methods Records of patients who were referred to the National Taiwan University Hospital for investigation of primary aldosteronism from January 1995 through December 2007 were retrieved. Primary aldosteronism was diagnosed based on the modified 4-corners criteria, otherwise essential hypertension was diagnosed. In both groups, the PUKC/BMI ratio was determined as well as the ARR. Bland–Altman and mountain-plot analysis were used to validate the agreement between ARR and PUKC/BMI. Receiver operating characteristic (ROC) curves were used to compare the sensitivity and specificity of PUKC/BMI and ARR. Results The records for urinary potassium were analyzed for 177 hypertensive patients (134 patients with primary aldosteronism). ROC curves showed comparable areas under the curves of both methods (95% CI: − 0.029 to 0.183; p = 0.186). Bland–Altman analysis further supported the agreement between ARR and PUKC/BMI ratio. Conclusions We found that the screening power of PUKC/BMI was as good as that of conventional ARR. With the quick and extensive availability of the PUKC/BMI method and its equivalence to ARR, this screening strategy would be a good first-line tool for massive community-based primary aldosteronism surveys.

Background. Renal vascular resistance [resistive index (RI)] has been associated with albuminuria in patients with type 2 diabetes. We studied the correlations between renal artery RI and urinary albumin excretion in adolescents and young adults. Methods. From May 2006 through September 2008, we established a cohort of adolescents and young adults based on previous history of elevated blood pressure (EBP) or normal blood pressure in childhood. This cohort was selected from the 1992–2000 nationwide mass urine screening of school children aged 6–18 years in Taiwan. From October through December 2008, we called back these adolescents and young adults living in Taipei to participate in a renal vascular stiffness study. Linear mixed regression models were applied to study the correlation between renal artery RI and urinary albumin excretion after controlling for cardiovascular (CV) risk factors. Results. Of the 147 subjects enrolled in this study, 67 had macroalbuminuria, 36 had microalbuminuria and 44 had normoalbuminuria. Except for high-density lipoprotein cholesterol, most CV risk factors did not differ significantly among these three groups. Mean RI were similar for the three groups. Neither log (urinary albumin concentration) nor log (urinary albumin:creatinine ratio) correlated with RI. Step-wise linear mixed regression models showed that RI was significantly associated only with male gender and diastolic blood pressure, but not with urinary albumin excretion or EBP in childhood. Conclusion. Renal artery RI is not associated with urinary albumin excretion in nondiabetic adolescents and young adults.

Objective: Current data on primary aldosteronism (PA) from Asian populations are scarce. This cohort study clarifies the attributes of patients with PA in a typical Chinese population. Design: An observational cohort study. Methods: The records of patients referred to the Hypertension Clinic from a multi-centre registration in Taiwan from January 1995 to December 2007 were reviewed. All patients with PA were classified into two subtypes: aldosterone-producing adenomas (APA) and idiopathic hyperaldosteronism (IHA); their characteristics were compared. Results: Our cohort consisted of 346 patients with PA, 255 with APA and 91 with IHA. The initial hypokalaemia (59% in APA vs. 27.5% in IHA, p < 0.0001) and transtubular potassium gradient (TTKG) (6.30 ± 2.41 in APA vs. 4.91 ± 2.03 in IHA, p = 0.01) were higher in the APA group. Baseline plasma aldosterone concentration (PAC) was also significantly different between the two subgroups (49.96 ± 38.15 ng/dl in APA vs. 34.24 ± 21.47 in IHA, p < 0.0001). Conclusions: In typical Chinese PA patients, the APA subgroup had a higher proportion of hypokalaemia with elevated TTKG and higher PAC as compared with the IHA subgroup. This largest Asian database also demonstrated major differences between the Caucasian and Chinese populations including female predilection, frequent hypokalaemia, and common paralytic myopathy.

The ratio of aldosterone-to-renin activity is currently recommended as a screening test for primary aldosteronism (PA). There are many factors interfering the interpretation of aldosterone-renin ratio (ARR) and could hamper in-time diagnosis of PA. Here, we first report a patient with underlying Page phenomenon and an accidentally disclosed adrenal incidentaloma. High renin secretion from Page phenomenon had masked higher ARR into normal ARR obscuring the diagnosis of PA. However, adrenal venous sampling (AVS) confirmed the autonomous aldosterone secretion with left adrenal vein plasma aldosterone concentration (PAC) 124.1 ng/dl and a lateralization ratio 3.3. AVS may discriminate masked PA due to high renin secretion from Page kidney. It is suggested that clinicians should cautiously interpret aldosterone-renin ratio and consider diagnostic AVS if hyperaldosteronism is highly suspected especially in the background of other secondary hypertension.

Background A common pharmacologic test for the diagnosis of primary aldosteronism (PA) is the administration of captopril to determine whether an abnormal plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio(ARR) persists, although active renin concentration (ARC) may offer advantages with regard to processing and standardization. Methods A prospective, head-to-head study was conducted between Feb 2008 and Dec 2008. One hundred and fourteen patients enrolled and received captopril to aid in the diagnosis of PA in the TAIPAI intervention. Results Fifty-one patients were diagnosed with PA. Post-captopril ARC was significantly correlated with PRA. The area under the receiver operating characteristic curve of the post-captopril ARR was not different in PRA vs ARC measurements. When post-captopril ARC-based ARR (ARRARC) > 35.5 as the cut-off value, we obtained sensitivity of 75.0% and specificity of 86.4% to differentiate PA from essential hypertension. Conclusions The correlation of individual PRA and ARC after administration of captopril was excellent; especially at the lower PRA levels. Post-captopril ARRARC values used to diagnose PA are not different from post-captopril PRA-based (ARRPRA) values in patients without kidney, liver and heart failures. Primary aldosteronism can be diagnosed with a post-captopril cut-off value of ARRARC > 35.5 pmol/ng.

Long-term exposure to arsenic is a major public health concern. Emerging evidence suggests adverse health effects even at low levels of exposure. This study examined the association of arsenic exposure with estimated glomerular filtration rate (eGFR) and compared methods of adjustment for urinary dilution in a representative sample of U.S. adolescents and young adults.We performed a cross-sectional study of 1253 participants ages 12-30 years in the 2009-2012 National Health and Nutrition Examination Survey (NHANES) with available urinary arsenic and eGFR measures. Multivariable linear regression was used to model the association of urinary total arsenic and dimethylarsinate (DMA) with eGFR.The median urinary total arsenic and DMA concentrations were 6.3 μg/L (IQR 3.3-12.7 μg/L) and 3.3 μg/L (IQR 1.7-5.7 μg/L), respectively. Median eGFR was 109 mL/min/1.73 m(2). Adjusting arsenic for urine concentration with urinary creatinine, eGFR was 4.0 mL/min/1.73 m(2) higher (95% confidence interval [CI] 1.0-7.1 mL/min/1.73 m(2)) and 4.3mL/min/1.73 m(2) higher (95% CI 0.5-8.0 mL/min/1.73 m(2)) per log-unit increase in total arsenic and DMA, respectively. When using urine osmolality to adjust for urine concentration, a log-unit increase in total arsenic and DMA was associated with a 0.4 mL/min/1.73 m(2) (95% CI -1.8 to 1.1 mL/min/1.73 m(2)) and 0.01 (95% CI -1.9 to 1.9 mL/min/1.73 m(2)) lower eGFR, respectively.Discordant associations were observed between arsenic and eGFR levels depending on whether urinary creatinine or osmolality was used to adjust for urine concentration. Further study should be dedicated to validating the best approach to account for urinary dilution in research in toxicants, and this may have implications for all studies which examine urinary biomarkers.

Background For many environmental chemicals, concentrations in spot urine samples are considered valid surrogates of exposure and internal dose. To correct for urine dilution, spot urine concentrations are commonly adjusted for urinary creatinine. There are, however, several concerns about the use of urine creatinine. While urine osmolality is an attractive alternative; its characteristics and determinants in the general population remain unknown. Our objective was to describe the determinants of urine osmolality and to contrast the difference between osmolality and creatinine in urine. Methods From the National Health and Nutrition Examination Survey (NHANES) (2009–2010), 10,769 participants aged 16 years or older with measured urine osmolality and creatinine were used in the analysis. Very dilute and very concentrated urine was defined as urine creatinine lower than 0.3 g/l and higher than 3 g/l, respectively. Linear and logistic regression analyses were performed to investigate the associations of interest. Results Urine osmolality and creatinine were highly correlated (Pearson correlation coefficient=0.75) and their respective median values were 648 mOsm/kg and 1.07 g/l. The prevalence of very dilute and very concentrated urine samples was 8.1% and 3.1%, respectively. Factors associated in the same direction with both urine osmolality and urine creatinine included age, sex, race, body mass index (BMI), hypertension, water intake, and blood osmolality. The magnitude of associations expressed as percent change was significantly stronger with creatinine than osmolality. Compared to urine creatinine, urine osmolality did not vary by diabetes status but was affected by daily total protein intake. Participants with chronic kidney disease (CKD) had significantly higher urine creatinine concentrations but lower urine osmolality. Both very dilute and concentrated urine were associated with a diverse array of sociodemographic, medical conditions, and dietary factors. For instance, females were approximately 3.3 times more likely to have urine over-dilution than male [the adjusted odds ratios (95% CI)=3.27 (2.10–5.10)]. Conclusion Although the determinants of urine osmolality were generally similar to those of urine creatinine, the relative influence of socio-demographic and medical conditions was less on urine osmolality than on urine creatinine. Protocols for spot urine sample collection could recommend avoiding excessive and insufficient water intake before urine sampling to improve urine adequacy. The feasibility of adopting urine osmolality adjustment and water intake recommendations before providing spot urine samples for environmental biomonitoring merits further investigation.

The clinical spectrum of infections caused by non-typhoid Salmonella spp. includes gastroenteritis, enteric fever, bacteremia, and extraintestinal localized complications, especially in immunocompromised hosts. Here we report a patient with severe aplastic anemia developing left iliopsoas abscess caused by non-typhoid Salmonella (NTS), which was successfully treated by prolonged antibiotic treatment and repeated debridement. Our data indicate that aplastic anemia is a risk factor for infection caused by NTS.

Context: Primary aldosteronism (PA) is associated with a higher incidence of cardiovascular events, probably through mineralocorticoid receptor (MR)-dependent endothelial cell dysfunction, in comparison with essential hypertension (EH). Objective: Our objective was to investigate the number and function of endothelial progenitor cells (EPC) in PA and the relationship with arterial stiffness and disease progression. Design and Setting: We conducted a prospective study of the change of EPC number and outcome of PA patients after treatment at a tertiary medical center. Primary Outcomes: Changes in arterial stiffness and EPC number after treatment and the curability of hypertension were assessed. Patients: A total of 113 PA patients (87 patients diagnosed with aldosterone-producing adenoma, 26 with idiopathic hyperaldosteronism) and 55 patients with EH participated. Results: PA patients had higher arterial stiffness than EH patients (P = 0.006), with a lower numbers of circulating EPC and endothelial colony-forming units (P < 0.05). The differences were ameliorated at 6 months after unilateral adrenalectomy or treatment with spironolactone. Expression of MR was identified in the EPC. The number of circulating EPC was inversely correlated with the plasma aldosterone concentration (P = 0.021), arterial stiffness (P = 0.029) and serum high-sensitivity C-reactive protein (P = 0.03). High-dose aldosterone (10−5 and 10−6m) attenuated EPC proliferation and angiogenesis in vitro. Among the 45 patients who underwent unilateral adrenalectomy, 32 (71%) were cured of hypertension. The preoperative number of EPC [log(EPC number percent) >−3.6] predicted the curability of hypertension after adrenalectomy (P = 0.003). Conclusions: The relative deficiency of EPC in PA patients may contribute to aldosterone vasculopathy, which can be reversed by adrenalectomy and spironolactone. High aldosterone levels attenuated EPC proliferation and angiogenesis. Circulating EPC number may be a valuable biomarker to identify PA patients with a high incidence of arterial stiffness and to predict postoperative residual hypertension of aldosterone-producing adenoma.

Purpose: To assess the degree of myocardial fibrosis in patients with primary aldosteronism (PA). Materials and Methods: Twenty-five patients with PA and 12 age-matched healthy volunteers underwent cine and late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) on a 1.5 T MR system. From volume–time curves of cine MRI, the time for deceleration (Tdec) was determined to assess the left ventricle (LV) chamber stiffness. Based on phase-sensitive reconstructed LGE images, a fibrosis index called enhancement value (EV) was computed as the signal intensity change in the myocardium over blood before and after contrast. Both Tdec and EV were compared between patients and controls. The association between Tdec and EV was investigated. Results: Patients showed a significantly higher EV (0.43 ± 0.05 vs. 0.36 ± 0.07; P = 0.002) and a significantly shorter Tdec (11.5 ± 3.5 %RR vs. 15.3 ± 2.4 %RR; P = 0.004) than controls. Significant correlations between EV and Tdec were observed in patients (r = −0.46, P = 0.018), in controls (r = −0.68, P = 0.015) and in all subjects (r = −0.63, P < 0.001). Conclusion: The fibrosis index is increased in patients with PA and the increase imposes an adverse effect on LV diastolic function. J. Magn. Reson. Imaging 2012;35:1349–1355. © 2012 Wiley Periodicals, Inc.

Primary aldosteronism (PA) is associated a worse cardiovascular outcome than essential hypertension. Hypokalemia, which is one major characteristic of PA, can affect both cardiac structure and function. The goal of this study is to evaluate the influence of serum potassium level on left ventricular (LV) mass and function in PA patients.We prospectively analysed 85 PA patients from October 2006 to September 2008 and 27 essential hypertension patients as the control group (group 1). Thirty-two patients with serum potassium3·5 mmol L(-1) were defined as hypokalemia (group 2), and 53 patients with serum potassium ≥ 3·5 mmol L(-1) were defined as normokalemia (group 3). Echocardiography including tissue Doppler image (TDI) recordings was performed in all patients.Group 2 patients had significant higher systolic and diastolic blood pressure (DBP), log-transformed plasma aldosterone concentration, log-transformed aldosterone-to-renin ratio and lower serum potassium level than groups 1 and 3. In echocardiographic measurement, group 2 patients had higher LV mass index (LVMI) than groups 1 and 3. In multivariate analysis for factors affecting LVMI in PA patients, only serum potassium level (P = 0·001), use of spironolactone (P = 0·004) and DBP (P = 0·005) were independent factors. In the TDI study, both groups 2 and 3 had lower e' and E/e' values than group 1.Serum potassium level is significantly associated with LVMI in PA patients. Compared with essential hypertensive patients, PA patients had a greater impairment of cardiac diastolic function.