Oxidative Stress-Induced Alterations of Cellular Localization and Expression of Aquaporin 1 Lead to Defected Water Transport upon Peritoneal Fibrosis.

Being one of the renal replacement therapies, peritoneal dialysis (PD) maintains around 15% of end-stage kidney disease patients' lives; however, complications such as peritoneal fibrosis and ultrafiltration failure during long-term PD compromise its application. Previously, we established a sodium hypochlorite (NaClO)-induced peritoneal fibrosis porcine model, which helped to bridge the rodent model toward pre-clinical human peritoneal fibrosis research. In this study, the peritoneal equilibration test (PET) was established to evaluate instant functional changes in the peritoneum in the pig model. Similar to observations from long-term PD patients, increasing small solutes transport and loss of sodium sieving were observed. Mechanistic investigation from both in vivo and in vitro data suggested that disruption of cytoskeleton induced by excessive reactive oxygen species defected intracellular transport of aquaporin 1, this likely resulted in the disappearance of sodium sieving upon PET. Functional interference of aquaporin 1 on free water transport would result in PD failure in patients.

Prognostic Significance of Frontal QRS-T Angle in Patients with Idiopathic Dilated Cardiomyopathy.

BACKGROUND: Current risk stratification of idiopathic dilated cardiomyopathy (IDC) lacks sufficient sensitivity and specificity. The objective of this study was to investigate the predictive role of frontal QRS-T angles in IDC. METHODS: A prospective study with 509 IDC patients was performed from February 2008 to December 2013 in the Affiliated Drum Tower Hospital, Nanjing University School of Medicine. Baseline values and changes in QRS-T angles were recorded. Follow-up was conducted every 6 months. Analyses by Cox Proportional Hazards model were performed to evaluate the association between QRS-T angle and outcomes. The primary outcome of interest was all-cause mortality. RESULTS: During a median follow-up of 34 months, 90 of 316 patients with QRS-T angles >90° died compared to 31 of 193 patients with QRS-T angles ≤90° (hazard ratio [HR] =2.4, P < 0.001). Cardiac death was more prevalent in patients with a wide QRS-T angle (HR = 2.4, P < 0.001), similar to heart failure rehospitalization (HR = 2.5, P < 0.001). After adjustment for potential prognostic factors, the QRS-T angle was independently associated with all-cause mortality (HR = 2.5, P < 0.05), cardiac mortality (HR = 1.9, P < 0. 05), and heart failure rehospitalization (HR = 2.3, P < 0.01). Optimized therapy significantly narrowed the frontal QRS-T angle (100.9 ± 53.4° vs. 107.2 ± 54.4°, P < 0.001). The frontal QRS-T angle correlated well with established risk factors, such as left ventricular ejection fraction, brain natriuretic peptide, and New York Heart Association functional class. CONCLUSIONS: The frontal QRS-T angle is a powerful predictor of all-cause mortality, cardiac mortality, and worsening heart failure in IDC patients, independent of well-established prognostic factors. Optimized therapy significantly narrows the QRS-T angle, which might be an indicator of medication compliance, but this requires further investigation.