Viability Of Peritoneal Mesothelial Cells Research Articles

Activation of salt-inducible kinase 2 promotes the viability of peritoneal mesothelial cells exposed to stress of peritoneal dialysis.

Maintaining mesothelial cell viability is critical to long-term successful peritoneal dialysis (PD) treatment. To clarify the viability mechanism of peritoneal mesothelial cells under PD solutions exposure, we examined the mechanisms of cellular response to this stress conditions. Here we report that the proteasome activity is inhibited when treated with PD solutions. Proteasome inhibition-mediated activation of salt-inducible kinase 2 (SIK2), an endoplasmic reticulum-resident protein, is important for mesothelial cell viability. SIK2 is mobilized to promote autophagy and protect the cells from apoptosis under PD solution or MG132 treatment. Immunofluorescence staining showed that SIK2 is colocalized with LC3B in the autophagosomes of mesothelial cells treated with PD solution or derived from patients undergoing PD treatment. SIK2 activation is likely via a two-step mechanism, upstream kinases relieving the autoinhibitory conformation of SIK2 molecule followed by autophosphorylation of Thr175 and activation of kinase activity. These results suggest that activation of SIK2 is required for the cell viability when proteasome activity is inhibited by PD solutions. Maintaining or boosting the activity of SIK2 may promote peritoneal mesothelial cell viability and evolve as a potential therapeutic target for maintaining or restoring peritoneal membrane integrity in PD therapy.

Randomized controlled study of biocompatible peritoneal dialysis solutions: Effect on residual renal function

Residual kidney function is important for patient and technique survival in peritoneal dialysis (PD). Biocompatible dialysis solutions are thought to improve function and viability of peritoneal mesothelial cells and to preserve residual renal function (RRF). We conducted a randomized controlled study comparing use of biocompatible (B) with standard (S) solutions in 93 incident PD patients during a 1-year period. The demographics, comorbidities, and RRF of both groups were similar. At 3 and 12 months, 24-h urine samples were collected to measure volume and the mean of urea and creatinine clearance normalized to body surface area. Surrogate markers of fluid status, diuretic usage, C-reactive protein concentration, peritonitis episodes, survival data, and peritoneal equilibrium tests were also collected. Changes in the normalized mean urea and creatinine clearance were the same for both groups, with no significant differences in secondary end points. Despite non-randomized studies suggesting benefits of these newer biocompatible solutions, we could not detect any clinically significant advantages. Additional studies are needed to determine if advantages are seen with longer term use.

In vitro testing of a potentially biocompatible continuous ambulatory peritoneal dialysis fluid.

In the present study a newly formulated dialysis solution (HDF) was tested for its effects on phagocyte viability and function as well as its ability to support bacterial growth. This solution differs from standard CAPD solution (NPD) by the inclusion of histidine to buffer the fluid to pH 6.7. Low-dextrose HDF (1.36% w/v dextrose) did not significantly decrease the viability or inhibit any of the PMN functional parameters measured (phagocytosis, LTB4 release or respiratory burst activation) when compared to control buffer. NPD (1.36% w/v dextrose) at low pH as well as all high-dextrose dialysis solutions (NPD and HDF) significantly inhibited most PMN functions independently of reduced viability. Peritoneal mesothelial cell viability was unaffected by either low- or high-dextrose HDF but was significantly reduced by NPD (1.36 and 3.86% dextrose) at pH 5.2. The inhibitory effects of low dextrose dialysis solutions were confirmed as being partly related to their low initial pH. High-dextrose dialysis fluids, however, inhibit PMN function by a mechanism which, in addition to initial pH, appears to be directly related to their dextrose content but not their osmolality.