Abstract. Calcification complications are frequent among longterm dialysis patients. However, the prognostic implication of cardiac valve calcification in this population is not known. This study aimed to determine if cardiac valve calcification predicts mortality in long-term dialysis patients. Baseline echocardiography was performed in 192 patients (mean Ϯ SD age, 55 Ϯ 12 yr) on continuous ambulatory peritoneal dialysis (mean Ϯ SD duration of dialysis, 39 Ϯ 31 mo) to screen for calcification of the aortic valve, mitral valve, or both. Valvular calcification was present in 62 patients. During the mean follow-up of 17.9 mo (range, 0.6 to 33.9 mo), 46 deaths (50% of cardiovascular causes) were observed. Overall 1-yr survival was 70% and 93% for patients with and without valvular calcification (P Ͻ 0.0001, log-rank test). Cardiovascular mortality was 22% and 3% for patients with and without valvular calcification (P Ͻ 0.0001). Multivariable Cox regression analysis showed that cardiac valve calcification was predictive of an increased allcause mortality (hazard ratio [HR], 2.50; 95% CI, 1.32 to 4.76; P ϭ 0.005) and cardiovascular death (HR 5.39; 95% CI, 2.16 to 13.48; P ϭ 0.0003) independent of age, male gender, dialysis duration, C-reactive protein, diabetes, and atherosclerotic vascular disease. Eighty-nine percent of patients with both valvular calcification and atherosclerotic vascular disease, 23% of patients with valvular calcification only, 21% of patients with atherosclerotic vascular disease only, and 13% of patients with neither complication died at 1-yr (P Ͻ 0.0005). The cardiovascular death rate was 85% for patients with both complications, 13% for patients with valvular calcification only, 14% for patients with atherosclerotic vascular disease only, and 5% for those with neither complication (P Ͻ 0.0005). The number of calcified valves was associated with all-cause mortality (P Ͻ 0.0005) and cardiovascular death (P Ͻ 0.0005). One-year all-cause mortality was 57% for patients with both aortic and mitral valves calcified, 40% for those with either valve calcified, and 15% for those with neither valve calcified. In conclusion, cardiac valve calcification is a powerful predictor for mortality and cardiovascular deaths in long-term dialysis patients. Valvular calcification by itself has similar prognostic importance as the presence of atherosclerotic vascular disease. Its coexistence with other atherosclerotic complications indicates more severe disease and has the worst outcome. awang@cuhk.edu.hkVascular or tissue calcification is increasingly recognized to be a frequent complication in patients with end-stage renal disease (ESRD). Braun et al. (1) reported that two thirds of the adult hemodialysis patients had electron beam computed tomographic (EBCT) evidence of coronary artery calcification (CAC) and that over half had cardiac valve calcification. The calcification score in dialysis patients was not only substantially higher than age-matched and gender-matched patients with angiographically confirmed c...

Serum fetuin-A showed important associations with valvular calcification, atherosclerosis, malnutrition and inflammation, and was linked to mortality and cardiovascular events in PD patients via its close relationships with the MIAC syndrome.

In patients with HBeAg-positive chronic hepatitis B, staggered combination treatment with pegylated interferon-alpha2b and lamivudine may lead to a higher rate of virologic response than lamivudine monotherapy.

Abstract. C-reactive protein (CRP), the prototype marker of inflammation, and cardiac hypertrophy are important prognostic indicators in dialysis patients. Residual renal function (RRF) has also been shown to influence survival of peritoneal dialysis (PD) patients. This study examined the relations between inflammation, RRF, and left ventricular hypertrophy (LVH) and determined whether inflammation, RRF, and LVH combine adversely to predict the outcomes of PD patients. A prospective observational study was performed in 231 chronic PD patients. Left ventricular mass index (LVMi), residual glomerular filtration rate (GFR), CRP, hemoglobin, serum albumin, and BP were determined at study baseline and related to outcomes. On univariate analysis, age (P ϭ 0.002), dialysis duration (P ϭ 0.004), coronary artery disease (P Ͻ 0.001), pulse pressure (P Ͻ 0.001), hemoglobin (P Ͻ 0.001), serum albumin (P ϭ 0.032), log-CRP (P Ͻ 0.001), and GFR (P Ͻ 0.001) were significantly associated with log-LVMi. Log-CRP was positively correlated with pulse pressure (R ϭ 0.218, P ϭ 0.001) and negatively correlated with GFR (R ϭ Ϫ0.272, P Ͻ 0.001). Multivariate analysis showed that log-CRP (P ϭ 0.008) and RRF (P ϭ 0.003) remained associated with log-LVMi independent of hemoglobin, serum albumin, arterial pulse pressure, and coronary artery disease. After follow-up for 30 Ϯ 14 mo, 34.2% patients had died. CRP, RRF, and LVMi each were significantly predictive of all-cause mortality and cardiovascular death. Kaplan-Meier analysis showed a significant increase in all-cause (P Ͻ 0.0001) and cardiovascular mortality (P Ͻ 0.0001) as the number of risk factors, namely CRP Ն50th percentile, no RRF, and LVMiՆ 50th percentile increased with the 2-yr all-cause mortality and cardiovascular death reaching as high as 61% and 46%, respectively, for patients who had all three risk factors. Compared with patients with none of the three risk factors, those with all three risk factors had an adjusted hazards ratio of 6.94 (P Ͻ 0.001) and 5.43 (P ϭ 0.001) for all-cause mortality and cardiovascular mortality, respectively. In conclusion, inflammation, RRF, and LVH are interrelated and combine adversely to increase mortality and cardiovascular death risk of PD patients.Left ventricular hypertrophy (LVH) is a major cardiovascular complication and an important predictor for mortality in end stage renal disease (ESRD) patients (1,2). Other than hypertension, anemia, and hypoalbuminemia, well-known factors for LVH in ESRD (3), the worsening of LVH with decline in renal function in predialysis patients (4) as well as the regression of LVH after successful kidney transplantation (5) supports a link between renal function and LVH. Our group recently demonstrated a significant cross-sectional relationship between residual renal function (RRF) and LVH in nondiabetic ESRD patients who were receiving peritoneal dialysis (PD) therapy (6). The exact mechanisms for this association are unclear, but our data suggested that uremia, worsening anemia, and hypoalbuminemia with decl...

Interleukin (IL)-33 belongs to IL-1 cytokine family which is constitutively produced from the structural and lining cells including fibroblasts, endothelial cells, and epithelial cells of skin, gastrointestinal tract, and lungs that are exposed to the environment. Different from most cytokines that are actively secreted from cells, nuclear cytokine IL-33 is passively released during cell necrosis or when tissues are damaged, suggesting that it may function as an alarmin that alerts the immune system after endothelial or epithelial cell damage during infection, physical stress, or trauma. IL-33 plays important roles in type-2 innate immunity via activation of allergic inflammation-related eosinophils, basophils, mast cells, macrophages, and group 2 innate lymphoid cells (ILC2s) through its receptor ST2. In this review, we focus on the recent advances of the underlying intercellular and intracellular mechanisms by which IL-33 can regulate the allergic inflammation in various allergic diseases including allergic asthma and atopic dermatitis. The future pharmacological strategy and application of traditional Chinese medicines targeting the IL-33/ST2 axis for anti-inflammatory therapy of allergic diseases were also discussed.

IL-17A and IL-17F are members of the IL-17 family that play crucial roles in allergic inflammation. Recent studies reported that IL-17A and IL-17F production from a distinct Th lymphocyte subset, Th17, was specifically induced by IL-23, which was produced by dendritic cells and macrophages in response to microbial stimuli. The IL-23-IL-17 axis might therefore provide a link between infections and allergic diseases. In the present study, we investigated the effects of IL-17A, IL-17F, and IL-23, alone or in combination, on cytokine and chemokine release from eosinophils and the underlying intracellular mechanisms. Human eosinophils were found to constitutively express receptors for IL-17A, IL-17F, and IL-23 at the protein level. IL-17A, IL-17F, and IL-23 could induce the release of chemokines GRO-α/CXCL1, IL-8/CXCL8, and MIP-1β/CCL4 from eosinophils, while IL-17F and IL-23 could also increase the production of proinflammatory cytokines IL-1β and IL-6. Synergistic effects were observed in the combined treatment of IL-17F and IL-23 on the release of proinflammatory cytokines, and the effects were dose-dependently enhanced by IL-23, but not IL-17F. Further investigations showed that IL-17A, IL-17F, and IL-23 differentially activated the ERK, p38 MAPK, and NF-κB pathways. Moreover, inhibition of these pathways using selective inhibitors could significantly abolish the chemokine release induced by IL-17A, IL-17F, and IL-23 and the synergistic increases on IL-1β and IL-6 production mediated by combined treatment of IL-17F and IL-23. Taken together, our findings provide insight for the Th17 lymphocyte-mediated activation of eosinophils via differential intracellular signaling cascades in allergic inflammation.

This study was performed to determine whether the N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is a useful biomarker in predicting cardiovascular congestion, mortality, and cardiovascular death and event in chronic peritoneal dialysis (PD) patients. A prospective cohort study was conducted in 230 chronic PD patients in a dialysis unit of a university teaching hospital. Serum NT-pro-BNP was measured at baseline together with echocardiography and dialysis indices. Each patient was followed for 3 yr from the day of enrollment or until death. Time to develop first episode of cardiovascular congestion and other cardiovascular event and time to mortality and cardiovascular death were studied in relation to NT-pro-BNP. NT-pro-BNP showed the strongest correlation with residual GFR, followed by left ventricular ejection fraction and left ventricular mass index. In the univariate Cox regression model, NT-pro-BNP was a significant predictor of cardiovascular congestion, mortality, and cardiovascular death and event. In the fully adjusted multivariable Cox regression analysis that included residual GFR, left ventricular ejection fraction, and left ventricular mass index, the hazard ratios for cardiovascular congestion, mortality, composite end point of mortality and cardiovascular congestion, and cardiovascular death and event for patients of the fourth quartile were 4.25 (95% confidence interval [CI] 1.56 to 11.62; P ‫؍‬ 0.005), 4.97 (95% CI 1.35 to 18.28; P ‫؍‬ 0.016), 5.03 (95% CI 2.07 to 12.26; P < 0.001), 7.50 (95% CI 1.36 to 41.39; P ‫؍‬ 0.021), and 9.10 (95% CI 2.46 to 33.67; P ‫؍‬ 0.001), respectively, compared with the first quartile. These data showed that NT-pro-BNP is an important risk predictor of cardiovascular congestion, mortality, and adverse cardiovascular outcomes in chronic PD patients and adds important prognostic information beyond that contributed by left ventricular hypertrophy, systolic dysfunction, and other conventional risk factors.

As compared to conventional PD solution, the use of balance, a neutral pH, low GDP solution resulted in a superior profile of PDE mesothelial cell marker and a lower degree of systemic inflammation, and the difference was maintained for 1 year. It remains to be determined whether these effects could result in better long-term clinical outcome.