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Background. The local peritoneal effects of low-glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF) have been extensively described. However, the systemic effects of prolonged prescription of these solutions are unknown. This study aimed to evaluate the effects of neutral pH and low-GDP PDF on systemic inflammation and endothelial dysfunction markers in peritoneal dialysis (PD) patients. Methods. This is a multicenter, open labeled, randomized controlled trial including one hundred fifty-two patients initiating continuous ambulatory peritoneal dialysis for end-stage renal disease from seven centers in Korea. Participants were randomly allocated to conventional PDF (Stay safe®; Fresenius Medical Care, Bad Homburg, Germany) or low-GDP PDF (Balance®; Fresenius Medical Care) and were followed for 1 year. Primary outcome variable was the inflammation and endothelial dysfunction index (IEDI), a composite score derived from serum levels of soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cellular adhesion molecule (sVCAM)-1 and high-sensitivity C-reactive protein (hs-CRP). sICAM-1, sVCAM-1, residual renal function (RRF), peritoneal membrane transport characteristics, ultrafiltration volume and nutritional parameters were measured as secondary outcome variables. Results. Of 152 patients randomized, 146 (low-GDP: conventional PDF, 79:67) patients entered the trial (46% male, 53% with diabetes mellitus). At 12-month follow-up, the low-GDP group had significantly lower levels of IEDI, sICAM-1 and sVCAM-1 compared to the conventional group; hs-CRP was not different between groups. Peritoneal transport characteristics, RRF, nutritional parameters, incidence of peritonitis and death-censored technique survival were not different between groups. Conclusion. Neutral pH and low-GDP PDF likely produce fewer changes in markers of endothelial dysfunction compared to conventional PDF in incident PD patients. [ABSTRACT FROM PUBLISHER]

Background A recent genome-wide association study has identified 5-hydroxytrytamine (serotonin) receptor 7, adenylate cyclase-coupled ( HTR7) as a risk gene for alcohol dependence. In addition, the serotonergic system has been considered as a modulator that plays an important role in alcohol use disorders. Functional, pharmacological, and genetic studies of serotonin neurotransmission have revealed that serotonin receptors are potential targets for the treatment of alcohol use disorders. The aim of this study is to investigate whether associations between HTR7 genetic polymorphisms and alcohol dependence could be replicated. Methods This study genotyped a total of 22 common single nucleotide polymorphisms ( SNPs) in 459 alcoholic patients and 444 nonalcoholic controls. Results Logistic regression analysis of the case-control study, controlling for age and sex as covariates, showed nominal associations of 7 SNPs ( p = 0.02 to 0.04; odds ratio = 0.60 to 1.35). In further linear regression analysis based on the Alcohol Use Disorders Identification Test score for alcohol dependence, 8 SNPs and 3 haplotypes showed relatively significant associations with alcohol dependence (minimum p = 0.001; p corr = 0.02). Conclusions Although further replications and functional evaluations are needed, our findings suggest that genetic variations of HTR7 may contribute to the predisposition for alcohol dependence. [ABSTRACT FROM AUTHOR]

Background: The impact of dialysis modality on survival is still somewhat controversial. Given possible differences in patients’ characteristics and the cause and rate of death in different countries, the issue needs to be evaluated in Korean cohorts. Methods: A nationwide prospective observational cohort study (NCT00931970) was performed to compare survival between peritoneal dialysis (PD) and hemodialysis (HD). A total of 1,060 end-stage renal disease patients in Korea who began dialysis between September 1, 2008 and June 30, 2011 were followed through December 31, 2011. Results: The patients (PD, 30.6%; HD, 69.4%) were followed up for 16.3±7.9 months. PD patients were significantly younger, less likely to be diabetic, with lower body mass index, and larger urinary volume than HD patients. Infection was the most common cause of death. Multivariate Cox regression with the entire cohort revealed that PD tended to be associated with a lower risk of death compared to HD [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.36–1.08]. In propensity score matched pairs (n = 278 in each modality), cumulative survival probabilities for PD and HD patients were 96.9% and 94.1% at 12 months (P = 0.152) and 94.3% and 87.6% at 24 months (P = 0.022), respectively. Patients on PD had a 51% lower risk of death compared to those on HD (HR 0.49, 95% CI 0.25–0.97). Conclusions: PD exhibits superior survival to HD in the early period of dialysis, even after adjusting for differences in the patients’ characteristics between the two modalities. Notably, the most common cause of death was infection in this Korean cohort. [ABSTRACT FROM AUTHOR]

Summary: Background: Voriconazole is a triazole agent with excellent antifungal activity against Aspergillus species. However, despite its potential advantages, the occurrence of unpredictable toxicities might be critical in immunocompromised patients. The aim of this study was to analyze risk factors for voriconazole-related severe adverse events (SAEs). Methods: This prospective observational study was conducted in Korean patients with hematological malignancies and invasive aspergillosis on intravenous voriconazole therapy between June 2008 and April 2009. Results: Of the 25 patients enrolled, eight (32%) showed voriconazole-related SAEs, which included hepatotoxicities (n =5), cardiac tachyarrhythmias (n =2), and neurotoxicity (n =1). Sex, age, underlying hematological malignancies, voriconazole dose, the co-administration of a proton pump inhibitor, and CYP2C19 genotype were not found to be related to the occurrence of SAEs. However, trough plasma concentrations of voriconazole were found to be significantly higher in the patients with an SAE: median 6.32mg/l (interquartile range (IQR) 2.86–9.71mg/l) vs. median 2.15mg/l (IQR 0.92–4.00mg/l); p =0.011. Receiver operating characteristic curve analysis identified a cut-off trough concentration for SAEs of 5.83mg/l (sensitivity 62.5% and specificity 94.1%). Furthermore, multivariate analysis showed that a trough concentration of ≥5.83mg/l was the only significant independent risk factor of an SAE. Conclusions: This study shows that therapeutic drug monitoring is indicated in patients with a voriconazole-related SAE and that dose adjustment is required if the trough concentration of voriconazole exceeds 5.83mg/l. [Copyright &y& Elsevier]