Better preservation of the peritoneum in rats exposed to amino acid-based peritoneal dialysis fluid.
BACKGROUND
Glucose-containing peritoneal dialysis fluids (PDF) show impaired biocompatibility, which is related partly to their high glucose content, presence of glucose degradation products, low pH, and lactate buffer, or a combination of these factors. In a rat chronic peritoneal exposure model, we compared effects of an amino acid-based PDF (AA-PDF) with a glucose-containing PDF on the peritoneal microcirculation and morphology.


METHODS
Two groups of rats received 10 mL of either fluid daily for 5 weeks via peritoneal catheters connected to implanted subcutaneous mini vascular access ports. Leukocyte-endothelium interactions in the mesenteric venules were investigated by intravital microscopy. Quantification of angiogenesis and fibrosis and inspection of the mesothelial cell layer were performed by light and electron microscopy.


RESULTS
Daily exposure to glucose-containing PDF resulted in a significant increase in the number of rolling leukocytes in mesenteric venules, whereas instillation of AA-PDF did not change the level of leukocyte rolling. Glucose-containing PDF evoked a significantly higher number of milky spots in the omentum, whereas this response was significantly reduced in animals exposed to the AA-PDF (p < 0.02). Chronic instillation of glucose-containing PDF induced angiogenesis in various peritoneal tissues, accompanied by fibrosis in the mesentery and parietal peritoneum. Quantitative morphometric evaluation of omentum and mesentery showed a clear trend toward less angiogenesis after treatment with the AA-PDF compared to the glucose-containing PDF, which reached statistical significance in the parietal peritoneum (p < 0.04). Instillation of AA-PDF resulted in approximately 50% reduction of fibrosis in the mesentery (p < 0.04) and approximately 25% reduction in the parietal peritoneum (p < 0.009) compared to glucose-containing PDF. Glucose-containing PDF damaged the mesothelial cell layer, whereas the mesotheium was intact after AA-PDF treatment, as evidenced by electron microscopy.


CONCLUSIONS
Our data in a rat chronic peritoneal exposure model clearly demonstrate reduced immune activation (evidenced by decreased number of rolling leukocytes and decreased induction of omental milky spots) and reduced neoangiogenesis, fibrosis, and mesothelial damage of the peritoneal membrane after treatment with AA-PDF compared to glucose-containing PDF.
Zareie
Mohammad
M
Department of Molecular Cell Biology, VU University Medical Center, Amsterdam, The Netherlands.
van Lambalgen
Anton A
AA
ter Wee
Piet M
PM
Hekking
Liesbeth H P
LH
Keuning
Eelco D
ED
Schadee-Eestermans
Inge L
IL
Faict
Dirk
D
Degréve
Bart
B
Tangelder
Geert-Jan
GJ
Beelen
Robert H J
RH
van den Born
Jacob
J
D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D015314:Dialysis Solutions / Q000737:chemistry / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects; D005355:Fibrosis; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000596:Amino Acids; D015314:Dialysis Solutions; C482915:Nutrineal