Background: β2-Microglobulin (β2MG) and carbonyl stress are reported to contribute to the development of dialysis-related amyloidosis. The aim of this study was to determine whether the purity of dialysate affects plasma levels of β2MG and pentosidine (a surrogate marker of carbonyl stress) in hemodialysis patients. Methods: Sixteen patients on hemodialysis with a polysulfone membrane participated in this study. We switched the dialysate from conventional dialysate (endotoxin level 0.055–0.066 endotoxin units (EU)/ml) to ultrapure dialysate (endotoxin level <0.001 EU/ml), followed patients for 6 months, and then switched back to conventional dialysate once again. Plasma levels of β2MG, pentosidine, CRP and interleukin-6 (IL-6) were determined before the switch to ultrapure dialysate, 1 and 6 months after the switch to ultrapure dialysate, and 1 month after the switch back to conventional dialysate. Results: The switch from conventional to ultrapure dialysate significantly decreased plasma levels of β2MG, from 30.1 ± 1.4 to 27.1 ± 1.4 mg/dl (p < 0.05) and pentosidine, from 1,535.8 ± 107.5 to 1,267.6 ± 102.9 nmol/l (p < 0.01) after 1 month of use. The change of dialysate also significantly decreased plasma levels of CRP, from 0.28 ± 0.09 to 0.14 ± 0.05 mg/dl (p < 0.05) and IL-6, from 9.4 ± 2.7 to 3.5 ± 0.8 pg/ml (p < 0.01) over the 1-month period. These changes in plasma levels of β2MG, pentosidine, CRP and IL-6 were maintained over 6 months after switching to ultrapure dialysate and returned to basal levels by switching back to a conventional dialysate. Conclusions: Ultrapure dialysate decreases plasma levels of β2MG, pentosidine and inflammatory markers in hemodialysis patients. The use of ultrapure dialysate might be useful in preventing and/or treating complications of dialysis, such as dialysis-related amyloidosis, atherosclerosis and malnutrition.
We previously identified apoptosis stimulating protein of p53 (Aspp1) as an endothelial-specific gene functioning in mouse embryogenesis. To investigate the in vivo role of Aspp1, we generated Aspp1 knockout mice by targeted disruption. Aspp1(-/-) embryos showed subcutaneous edema and disorganized lymphatic vasculature. Morphological changes in lymphatic endothelial cells and isolated lymphatic islands were detected in Aspp1(-/-) embryos. Lymphangiography by injecting dye subcutaneously into the embryonic forelimb showed defective lymphatic drainage function and obstruction in collecting lymphatic vessels of Aspp1(-/-) embryos. Interestingly, Aspp1(-/-) adult mice resolved these lymphatic functional defects seen during embryogenesis, but lymphangiography in Aspp1(-/-) adult mice revealed abnormal patterns in collecting lymphatic vessels. Since Aspp proteins reportedly enhance apoptotic activity of p53, we asked whether p53 deficiency also affected lymphatic vessel development. Analysis of p53 knockout or Aspp1; p53 double knockout mice showed that p53 loss did not affect lymphatic vessels. These results indicate that Aspp1 plays a crucial role in the initial assembly and function of lymphatic vessels during mouse development in a p53-independent manner. Here we report novel lymphatic vascular phenotypes in Aspp1(-/-) mice; subcutaneous edema detected only during embryogenesis, delayed lymphatic vessel formation, and mispatterned collecting lymphatic vessels.
Two peak levels of apoptotic cells occurred in UA-induced ARF. The first peak might play a role in UA-induced tubular damage, while the second one might represent the removal of excess regenerating cells during the recovery phase. Modulation of apoptotic cell death might be involved in the acquired resistance to rechallenge injury by UA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.