Apoptosis of mesothelial cells caused by unphysiological characteristics of peritoneal dialysis fluids.
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.
Alscher
Dominik M
DM
Division of General Internal Medicine and Nephrology, Department of Internal Medicine, Robert-Bosch-Hospital, Stuttgart, Germany. dominik.alscher@rbk.de
Biegger
Dagmar
D
Mettang
Thomas
T
van der Kuip
Heiko
H
Kuhlmann
Ulrich
U
Fritz
Peter
P
D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000737:chemistry / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology*; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007552:Isotonic Solutions; D019394:Ki-67 Antigen / Q000378:metabolism; D009336:Necrosis; D009994:Osmolar Concentration; D010968:Plasticizers / Q000009:adverse effects; D014021:Tissue Preservation
D015314:Dialysis Solutions; C072670:Hanks Balanced Salt Solution; D007552:Isotonic Solutions; D019394:Ki-67 Antigen; D010968:Plasticizers; D016650:Fluorescein-5-isothiocyanate