High Ultrafiltration Rate Is Associated with Increased All-Cause Mortality in Incident Hemodialysis Patients with a High Cardiothoracic Ratio.

A high ultrafiltration rate (UFR) is associated with increased mortality in hemodialysis patients. However, whether a high UFR itself or heart failure with fluid overload followed by a high UFR causes mortality remains unknown. In this study, 2615 incident hemodialysis patients were categorized according to their initial cardiothoracic ratios (CTRs) to assess whether UFR was associated with mortality in patients with high or low CTRs. In total, 1317 patients (50.4%) were women and 1261 (48.2%) were diabetic. During 2246 (1087−3596) days of follow-up, 1247 (47.7%) cases of all-cause mortality were noted. UFR quintiles 4 and 5 were associated with higher risks of all-cause mortality than UFR quintile 2 in fully adjusted Cox regression analysis. As the UFR increased by 1 mL/kg/h, the risk of all-cause mortality increased 1.6%. Subgroup analysis revealed that in UFR quintile 5, hazard ratios (HRs) for all-cause mortality were 1.91, 1.48, 1.22, and 1.10 for CTRs of >55%, 50−55%, 45−50%, and <45%, respectively. HRs for all-cause mortality were higher in women and patients with high body weight. Thus, high UFRs may be associated with increased all-cause mortality in incident hemodialysis patients with a high CTR, but not in those with a low CTR.

Trends of treated hepatitis B, hepatitis C, and tuberculosis infection in long-term hemodialysis patients in Taiwan: A nationwide survey in 2010-2018.

BACKGROUND/PURPOSE: Hepatitis B virus (HBV), hepatitis C virus (HCV), and tuberculosis (TB) infections affect patient morbidity and mortality and challenge infection control procedures within dialysis facilities. Thus, updated information on the yearly infection trends in the dialysis population is pivotal to preventing and improving the management of these infectious diseases. METHODS: This study used reimbursement data from the Taiwan National Health Insurance Research Database. Long-term hemodialysis (HD) patients were defined as those receiving regular HD for more than 3 months. Treated HBV, HCV, and TB cases were defined according to the diagnosis codes, together with specified prescriptions. Liver malignancy and liver-related mortality were determined by the disease diagnosis. RESULTS: The long-term HD population in Taiwan grew from 57,539 in 2010 to 74,203 in 2018. The mean number of treated HBV, HCV, and TB cases in the HD population was 254 (3.9 per thousand HD patients), 136 (2.0 per thousand), and 165 (2.6 per thousand), respectively. An increasing trend of treated viral hepatitis and a mildly decreasing trend in treated TB were observed. Liver outcome showed an increasing trend in liver malignancy prevalence and a stationary trend of liver-related mortality. Treated HBV and TB, liver malignancy, and liver-associated mortality were higher in men than women (all p < 0.001). The burden of liver complications was higher in southern Taiwan. CONCLUSION: The increasing yearly trend of treated HBV and HCV and a stable trend of treated TB provide evidence for further infection control management and risk population identification of the HD population.

Association between the risk of heart failure hospitalization and end-stage renal disease with digoxin usage in patients with cardiorenal syndrome: A population-based study.

Background: The management of the coexistence of heart disease and kidney disease is increasingly challenging for clinicians. Chronic kidney disease (CKD) is not only a prevalent comorbidity of patients with heart failure but has also been identified as a noteworthy risk factor for all-cause mortality and poor clinical outcomes. Digoxin is one of the commonest treatments for heart disease. There are few trials investigating the role of digoxin in patients with cardiorenal syndrome (CRS). This study aims to examine the association between digoxin usage and clinical outcomes in patients with CRS in a nationwide cohort. Method: We conducted a population-based study that included 705 digoxin users with CRS; each patient was age, sex, comorbidities, and medications matched with three non-users who were randomly selected from the CRS population. Cox proportional hazards regression analysis was conducted to estimate the effects of digoxin on the incidence of all-cause mortality, congestive heart failure (CHF) hospitalization, coronary artery disease (CAD) hospitalization, and end-stage renal disease (ESRD). Results: The all-cause mortality rate was significantly higher in digoxin users than in non-users (adjusted hazard ratio [aHR] = 1.26; 95% confidence interval [CI] = 1.09-1.46, p = 0.002). In a subgroup analysis, there was significantly high mortality in the 0.26-0.75 defined daily dose (DDD) subgroup of digoxin users (aHR = 1.49; 95% CI = 1.23-1.82, p<0.001). Thus, the p for trend was 0.013. With digoxin prescription, the CHF hospitalization was significantly higher [subdistribution HR (sHR) = 1.17; 95% CI = 1.05-1.30, p = 0.004], especially in the >0.75 DDD subgroup (sHR = 1.19; 95% CI = 1.01-1.41, p = 0.046; p for trend = 0.006). The digoxin usage lowered the coronary artery disease (CAD) hospitalization in the > 0.75 DDD subgroup (sHR = 0.79; 95% CI = 0.63-0.99, p = 0.048). In renal function progression, more patients with CRS entered ESRD with digoxin usage (sHR = 1.34; 95% CI = 1.16-1.54, p<0.001). There was a significantly greater incidence of ESRD in the < 0.26 DDD and 0.26-0.75 DDD subgroups of digoxin users (sHR = 1.32; 95% CI = 1.06-1.66, p = 0.015; sHR = 1.44; 95% CI = 1.18-1.75; p for trend<0.001). Conclusion: Digoxin should be prescribed with caution to patients with CRS.

Association of digoxin with mortality in patients with advanced chronic kidney disease: A population-based cohort study.

Digoxin is commonly prescribed for heart failure and atrial fibrillation, but there is limited data on its safety in patients with chronic kidney disease (CKD). We conducted a population-based cohort study using the pre-end stage renal disease (ESRD) care program registry and the National Health Insurance Research Database in Taiwan. Of advanced CKD patient cohort (N = 31,933), we identified the digoxin user group (N = 400) matched with age and sex non-user group (N = 2,220). Multivariable Cox proportional hazards and sub-distribution hazards models were used to evaluate the association between digoxin use and the risk of death, cardiovascular events (acute coronary syndrome, ischemic stroke, or hemorrhagic stroke) and renal outcomes (ESRD, rapid decline in estimated glomerular filtration rate-eGFR, or acute kidney injury). Results showed that all-cause mortality was higher in the digoxin user group than in the non-user group, after adjusting for covariates (adjusted hazard ratio, aHR 1.63; 95% CI 1.23-2.17). The risk for acute coronary syndrome (sub-distribution hazard ratio, sHR 1.18; 95% CI 0.75-1.86), ischemic stroke (sHR 1.42; 95% CI 0.85-2.37), and rapid eGFR decline (sHR 1.00 95% CI 0.78-1.27) was not significantly different between two groups. In conclusion, our study demonstrated that digoxin use was associated with increased mortality, but not cardiovascular events or renal function decline in advanced CKD patients. This finding warns the safety of prescribing digoxin in this population. Future prospective studies are needed to overcome the limitations of cohort study design.

Thiazide-associated hyponatremia attenuates the fracture-protective effect of thiazide: A population-based study.

BACKGROUND: Thiazide, a first-line therapy for hypertension, lowers blood pressure, increases bone mineral density, and reduces the risk of fractures. However, hyponatremia, an adverse effect of thiazide, is associated with increased risk of osteoporosis and fractures. It is currently unclear whether thiazide-associated hyponatremia (TAH) outweighs the protective effects of thiazide. METHODS: Using data from Taiwan's National Health Insurance Research Database, we identified patients who were prescribed thiazide between 1998 and 2010. Those diagnosed with hyponatremia within three years after initiation of thiazide were selected for the TAH group. Thiazide users without hyponatremia were selected for the control group. The association between TAH and fracture risk was further evaluated using multivariable Cox regression models adjusted for comorbidities and medications. Subjects were followed up from the index date until the appearance of a fracture, death, or the end of a 3-year period. RESULTS: A total of 1212 patients were included in the TAH group, matched with 4848 patients in the control group. The incidence rate of fracture was higher in the TAH group than in the control group (31.4 versus 20.6 per 1000 person-years). TAH was associated with a higher risk of total fractures (adjusted hazard ratio [aHR]: 1.47, 95% confidence interval [CI] = 1.15-1.88), vertebra fractures (aHR: 1.84, 95% CI = 1.12-3.01), and hip fractures (aHR: 1.66, 95% CI = 1.12-2.46) after controlling for comorbidities and other medications. CONCLUSIONS: Thiazide users with hyponatremia have a higher risk of fracture than thiazide users without hyponatremia. The fracture-protective effect of thiazide is attenuated by TAH.

Characterization of early gamma interferon (IFN-gamma) expression during murine listeriosis: identification of NK1.1+ CD11c+ cells as the primary IFN-gamma-expressing cells.

Though it is well established that gamma interferon (IFN-gamma) is crucial to the early innate defense of murine listeriosis, its sources remain controversial. In this study, intracellular cytokine staining of IFN-gamma-expressing splenocytes early after Listeria monocytogenes infection revealed that NK1.1(+), CD11c(+), CD8(+) T, and CD4(+) T cells expressed IFN-gamma 24 h after infection. Contrary to the previous report, most IFN-gamma(+) dendritic cells (DC) were CD8alpha(-) DC. Unexpectedly, almost all CD11c(+) IFN-gamma-expressing cells also expressed NK1.1. These NK1.1(+) CD11c(+) cells represented primary IFN-gamma-expressing cells after infection. In situ studies showed these NK1.1(+) CD11c(+) cells were recruited to the borders of infectious foci and expressed IFN-gamma. A significant NK1.1(+) CD11c(+) population was found in uninfected spleen, lymph node, blood, and bone marrow cells. And its number increased significantly in spleen, lymph node, and bone marrow after L. monocytogenes infection. Using interleukin-12 (IL-12) p40(-/-) mice, IFN-gamma expression was found to be largely IL-12 p40 dependent, and the number of IFN-gamma-expressing cells was only about one-third of that of wild-type mice. Moreover, the IFN-gamma expression was absolutely dependent on live L. monocytogenes infection, as no IFN-gamma was detected after inoculation of heat-killed L. monocytogenes. Our findings not only provide an insight into IFN-gamma expression after in vivo infection but may also change the current perceptions of DC and natural killer cells.