Circulating angiopoietin-like protein 2 levels and arterial stiffness in patients receiving maintenance hemodialysis: A cross-sectional study.

BACKGROUND AND AIMS: Chronic low-grade inflammation is receiving much attention as a critical pathology that induces various aging phenotypes, a concept known as "inflammaging". Uremic patients undergoing hemodialysis therapy show vascular aging phenotypes characterized by greater arterial stiffness and calcification compared to healthy controls of the same generation. In the current study, we investigated whether levels of inflammaging markers in the circulation were associated with vascular aging phenotypes in hemodialysis patients, as estimated by the cardio-ankle vascular index (CAVI). METHODS: We conducted a multicenter cross-sectional study of 412 patients receiving hemodialysis and evaluated the relationship between circulating hs-CRP or ANGPTL2 levels, as markers of inflammaging, and CAVI. RESULTS: Of 412 patients, 376 were analyzed statistically. While circulating hs-CRP levels had no significant association with CAVI, generalized linear models revealed that high circulating ANGPTL2 levels were significantly associated with increasing CAVI after adjustment for classical metabolic factors and hemodialysis-related parameters [ß 0.63 (95%CI 0.07-1.18)]. Exploratory analysis revealed that high circulating ANGPTL2 levels were also strongly associated with increased CAVI, particularly in patients with conditions of increased vascular mechanical stress, such elevated blood pressure [ß 1.00 (95%CI 0.23-1.76)], elevated pulse pressure [ß 0.75 (95%CI 0.52-0.98)], or excess body fluid [ß 1.25 (95%CI 0.65-1.84)]. CONCLUSIONS: We conclude that circulating levels of ANGPTL2 rather than hs-CRP are positively associated with CAVI in the uremic population and that ANGPTL2 could be a unique marker of progression of vascular aging in patients receiving hemodialysis.

The predictive role of serum calprotectin on mortality in hemodialysis patients with high phosphoremia.

BACKGROUND: The inflammatory mediator calprotectin (CPT, myeloid-related protein 8/14) is known as an endogenous ligand contributing to pathophysiology in inflammatory diseases. Serum CPT reportedly became a potential biomarker in these conditions, though there is no report predicting the prognosis in hemodialysis patients. The aim of this study is to investigate the predictive role of serum CPT on mortality in hemodialysis patients. METHODS: We conducted a multicenter, observational cohort study of 388 Japanese subjects undergoing hemodialysis. Serum CPT were measured using an ELISA. The potential associations between serum CPT and clinical variables were cross-sectionally examined. Multivariate Cox regression was used to estimate the association between serum CPT, high-sensitivity C reactive protein (hs-CRP), white blood cell (WBC) count and mortality. Median follow-up was 6.6 years. RESULTS: The median CPT level was 6108 ng/ml (median in healthy subjects, 2800) at baseline. Serum CPT positively correlated with WBC count (ρ = 0.54, P < 0.001) and hs-CRP values (ρ = 0.35, P < 0.001). In multivariate analysis, hs-CRP was an independent predictor of all-cause mortality after adjusting confounding factors (middle vs. low: hazard ratio [HR] 2.09, 95% confidence interval [CI] 1.23-3.66; high vs. low: 2.47, 1.40-4.47). In the analysis by stratum of phosphate levels, elevated CPT levels were significantly associated with all-cause mortality in the highest tertile (18.1; 3.15-345.9) among the high-phosphate group, but not among the low-phosphate group. CONCLUSIONS: Serum CPT would become a potential predictive marker on mortality in hemodialysis patients with high-phosphate levels.

Circulating angiopoietin-like protein 2 levels and mortality risk in patients receiving maintenance hemodialysis: a prospective cohort study.

BACKGROUND: Patients undergoing hemodialysis treatment have a poor prognosis, as many develop premature aging. Systemic inflammatory conditions often underlie premature aging phenotypes in uremic patients. We investigated whether angiopoietin-like protein 2 (ANGPTL 2), a factor that accelerates the progression of aging-related and noninfectious inflammatory diseases, was associated with increased mortality risk in hemodialysis patients. METHODS: We conducted a multicenter prospective cohort study of 412 patients receiving maintenance hemodialysis and evaluated the relationship between circulating ANGPTL2 levels and the risk for all-cause mortality. Circulating ANGPTL2 levels were log-transformed to correct for skewed distribution and analyzed as a continuous variable. RESULTS: Of 412 patients, 395 were included for statistical analysis. Time-to-event data analysis showed high circulating ANGPTL2 levels were associated with an increased risk for all-cause mortality after adjustment for age, sex, hemodialysis vintage, nutritional status, metabolic parameters and circulating high-sensitivity C-reactive protein levels {hazard ratio [HR] 2.04 [95% confidence interval (CI) 1.10-3.77]}. High circulating ANGPTL2 levels were also strongly associated with an increased mortality risk, particularly in patients with a relatively benign prognostic profile [HR 3.06 (95% CI 1.86-5.03)]. Furthermore, the relationship between circulating ANGPTL2 levels and mortality risk was particularly strong in patients showing few aging-related phenotypes, such as younger patients [HR 7.99 (95% CI 3.55-18.01)], patients with a short hemodialysis vintage [HR 3.99 (95% CI 2.85-5.58)] and nondiabetic patients [HR 5.15 (95% CI 3.19-8.32)]. CONCLUSION: We conclude that circulating ANGPTL2 levels are positively associated with mortality risk in patients receiving maintenance hemodialysis and that ANGPTL2 could be a unique marker for the progression of premature aging and subsequent mortality risk in uremic patients, except those with significant aging-related phenotypes.

[Allergic reaction against an emulsifier, HCO-60, contained in multamin and enocitabine].

We report two cases of an allergic reaction to HCO-60, which is used as an emulsifien for Multamin and enocitabine. A 55-year-old woman with M 4 Eo developed a high fever, urticaria and erythema after induction chemotherapy. After stopping the administration of Multamin, her fever and eruptions subsided. A 51-year-old woman with L 2 developed erythema and hypotension 30 minutes after the third administration of Multamin. When the patient was given enocitabine, she developed anaphylactic shock. During chemotherapy in patients with leukemia, it is important to distinguish the allergic reaction against Multamin-containing HCO-60 from infection and allergies to other drugs.