Oxidative damages in tubular epithelial cells in IgA nephropathy: role of crosstalk between angiotensin II and aldosterone

<p>Abstract</p> <p>Background</p> <p>Inhibition of the renin-angiotensin-aldosterone system (RAAS) slows down the progression of chronic renal diseases (CKD) including IgA nephropathy (IgAN). Herein, we studied the pathogenetic roles of aldosterone (Aldo) in IgAN.</p> <p>Methods</p> <p>Human mesangial cells (HMC) was activated with polymeric IgA (pIgA) from IgAN patients and the effects on the expression of RAAS components and TGF-β synthesis examined. To study the roles of RAAS in the glomerulotubular communication, proximal tubular epithelial cells (PTEC) was cultured with conditioned medium from pIgA-activated HMC with eplerenone or PD123319, the associated apoptotic event was measured by the generation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS).</p> <p>Results</p> <p>Polymeric IgA up-regulated the Aldo synthesis and aldosterone synthase expression by HMC. The release of TGF-β by HMC was up-regulated synergistically by AngII and Aldo and this was inhibited by incubation of HMC with losartan plus eplerenone. Cultured PTEC express the mineralocorticoid receptor, but not synthesizing aldosterone. Apoptosis, demonstrated by cleaved PARP expression and caspase 3 activity, was induced in PTEC activated by conditioned medium prepared from HMC cultured with pIgA from IgAN patients. This apoptotic event was associated with increased generation of NADPH oxidase and ROS. Pre-incubation of PTEC with PD123319 and eplerenone achieved complete inhibition of PTEC apoptosis.</p> <p>Conclusions</p> <p>Our data suggest that AngII and Aldo, released by pIgA activated HMC, served as mediators for inducing apoptosis of PTEC in glomerulo-tubular communications. Crosstalk between AngII and Aldo could participate in determining the tubular pathology of IgAN.</p

Implications of the Variability in Time to Isotopic Equilibrium in the Deuterium Dilution Technique

OBJECTIVE: To investigate the variability in isotopic equilibrium time under field conditions, and the impact of this variability on estimates of total body water (TBW) and body composition. DESIGN AND SETTING: Following collection of a fasting baseline urine sample, 10 women and 10 men were dosed with deuterium oxide (0.05 g/kg body weight). Urine samples were collected every hour for 8 h. The samples were analysed using isotope ratio mass spectrometry. Time to equilibration was determined using three commonly employed data analysis approaches. RESULTS: Isotopic equilibrium was reached by 50, 80 and 100% of participants at 4, 6 and 8 h, respectively. The mean group equilibration determined using the three different plateau determination methods were 4.8+/-1.5, 3.8+/-0.8 and 4.9+/-1.4 h. Isotopic enrichment, TBW, and percent body fat estimates differed between early (3-5 h), but not later sampling times (5-8 h). CONCLUSION: Although the three different plateau determination approaches resulted in differences in equilibration time, all suggest that sampling at 6 h or later will decrease the likelihood of error in body composition estimates resultant from incomplete isotopic equilibration in a small proportion of individuals

Assessment of body composition in Sri Lankan children: validation of biotechnical impedance prediction equation

Objective: To develop bioelectrical impedance analysis (BIA) equations to predict total body water (TBW) and fat-free mass (FFM) of Sri Lankan children