ABSTRACT
BACKGROUND: Dialysis patients are classified according to their peritoneal permeability as low transporter (LT, low solute permeability) or high transporter (HT, high solute permeability). Tight junction (TJ) proteins are critical to maintain ions, molecules and water paracellular transport through peritoneum. Exposure to peritoneal dialysis solutions causes damage to TJ in human peritoneal mesothelial cells (HPMCs). We analyzed the quantity, distribution and function of TJ proteins: claudin-1, -2 and -8, ZO-1 and occludin, in HPMC cultures from LT and HT patients. Since all-trans retinoic acid (ATRA) might modify the expression of TJ proteins, we studied its effect on HPMCs. METHODS: Control HPMCs were isolated from human omentum, while HT or LT cells were obtained from dialysis effluents. Cells were cultured in presence of ATRA 0, 50 or 100 nM. Transepithelial electrical resistance (TER) measurement, immunostaining and Western blot analyses were performed. RESULTS: HT exhibited lower TER than control and LT monolayers. Immunofluorescence for TJ was weak and discontinuous along the cell contour, in LT and HT. Furthermore, claudin-1, occludin and ZO-1 expressions were decreased. In all groups, claudin-2 was localized at nuclei. We observed that ATRA improved TJ distribution and increased TJ expression in HT. This retinoid did not modify claudin-2 and -8 expressions. All-trans retinoic acid decreased TER in HT, but had no effect in LT. CONCLUSIONS: Tight junctions were altered in HPMCs from dialyzed patients. The HT monolayer has lower TER than LT, which might be associated with the peritoneal permeability in these patients. ATRA might be a therapeutic alternative to maintain mesothelial integrity, since it improved TJ localization and expression.
Subject(s)
Dialysis Solutions/pharmacology , Peritoneal Dialysis , Peritoneum/metabolism , Tretinoin/pharmacology , Adult , Biological Transport/drug effects , Biopsy , Blotting, Western , Cells, Cultured , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Female , Gene Expression Regulation , Humans , Male , Middle Aged , Peritoneum/drug effects , Peritoneum/pathology , Permeability , Tight Junctions/drug effects , Tight Junctions/genetics , Young AdultABSTRACT
The increasing rates in incidence and prevalence of chronic kidney disease (CKD) are important challenges for health systems around the world, and are even more significant for undeveloped countries. In Mexico the prevalence of CKD seems to be similar to that in highly developed nations, with diabetes as the leading cause of CKD; however, human and economic resources seem to be insufficient for treatment needs. This is reflected in the unacceptably high mortality rates and in noncompliance with established standards and guidelines. Several measures need to be taken to improve this picture, such as more efficient programs for the prevention of obesity, diabetes, and hypertension. Organizing a national registry of patients with CKD is now a pressing need, as is a continuous search for additional funding and budgets to increase the number of qualified nephrologists and specialized nurses and to continue the much-needed research on CKD.