Apoptosis of mesothelial cells caused by unphysiological characteristics of peritoneal dialysis fluids
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Published on: July 19, 2018
Dominik M Alscher1, Dagmar Biegger, Thomas Mettang
1Division of General Internal Medicine and Nephrology, Department of Internal Medicine, Robert-Bosch-Hospital, Stuttgart, Germany. dominik.alscher@rbk.de
Abstract:
There is an ongoing debate as to which peritoneal dialysis fluids (PDFs) provide the best preservation of peritoneal cells. To investigate this topic further, we measured apoptosis and necrosis of cultured mesothelial cells (MCs) after exposure to different single unphysiological features of PDFs and PDFs for whole. MCs were incubated in buffers containing plasticizers, high osmolarity by sodium chloride, low pH, and high glucose for 0.5, 4, and 24 h. The same procedure was repeated with different PDFs. Apoptosis and necrosis were measured by FACS-analysis (annexin-FITC and propidium iodide). We found that plasticizers were clearly able to induce apoptosis after 24 h (18 +/- 4%). The same result was observed with high osmolarity by sodium chloride (17 +/- 5%), but not for high glucose (9 +/- 8%). All fluids with low pH (5.2) caused severe and almost complete necrosis (after 4 and 24 h). Incubation in neutral, two-compartment PDFs (glucose 4.25%) without plasticizers for 4 h showed no significant necrosis (3%), but after 24 h apoptosis was detectable in 10 +/- 9% and necrosis in 29 +/- 8% of MCs. In conclusion, after improving PDFs and introducing neutral fluids, further attention should be drawn to inducers of apoptosis. Apoptosis can be detected quite early (24 h) and is caused by plasticizers and high osmolarity.
Insights
Plasticizers and high sodium chloride osmolarity in peritoneal dialysis fluids (PDFs) induce cell damage. Further research should focus on identifying and mitigating these apoptosis inducers for better cell preservation.
Area of Science:
- Nephrology
- Cell Biology
- Biomaterials
Background:
- Peritoneal dialysis fluids (PDFs) are crucial for maintaining peritoneal cell health.
- The composition of PDFs can impact mesothelial cell (MC) viability.
- Ongoing debate exists regarding the optimal PDF formulation for cell preservation.
Purpose of the Study:
- To investigate the effects of individual unphysiological components and whole PDFs on mesothelial cell apoptosis and necrosis.
- To compare the cytoprotective effects of different PDF formulations.
Main Methods:
- Cultured mesothelial cells (MCs) were exposed to various PDF components (plasticizers, high NaCl osmolarity, low pH, high glucose) and complete PDFs.
- Apoptosis and necrosis were quantified using FACS analysis with annexin-FITC and propidium iodide staining.
- Incubation times ranged from 0.5 to 24 hours.
Main Results:
- Plasticizers and high NaCl osmolarity significantly induced apoptosis after 24 hours (18% and 17%, respectively).
- Low pH (5.2) resulted in severe necrosis within 4-24 hours.
- High glucose did not significantly induce apoptosis.
- Neutral, two-compartment PDFs showed minimal necrosis at 4 hours but induced apoptosis (10%) and necrosis (29%) by 24 hours.
Conclusions:
- Plasticizers and high osmolarity are key inducers of apoptosis in mesothelial cells.
- Low pH is highly cytotoxic, causing significant necrosis.
- While neutral PDFs improve cell preservation, further attention is needed to address early apoptosis induction by specific PDF components.
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