Long-term exposure to new peritoneal dialysis solutions: Effects on the peritoneal membrane.
BACKGROUND
Chronic exposure to peritoneal dialysis fluid (PDF) affects the peritoneum, but precise causative factors are incompletely understood. We examined the effects of standard and new PDF on peritoneal function and structure.


METHODS
Female Wistar rats received twice daily intraperitoneal infusions of a standard lactate-buffered 3.86% glucose PDF at pH 5.5 (Dianeal) (N= 12), a low glucose degradation product (GDP) containing bicarbonate/lactate-buffered 3.86% glucose PDF at pH 7.4 (Physioneal) (N= 12), a lactate-buffered amino acid-based PDF at pH 6.7 (Nutrineal) (N= 12) or Earle's Balanced Salt Solution at pH 7.4 (EBSS) (N= 12) during 12 weeks.


RESULTS
Net ultrafiltration was lower after treatment with standard PDF, but not with low-GDP bicarbonate/lactate-buffered and amino acid-based PDF, compared to EBSS. Peritonea exposed to standard PDF were characterized by an increased expression of vascular endothelial growth factor (VEGF), microvascular proliferation as well as submesothelial fibrosis, which were not observed in other groups. Staining for methylglyoxal adducts was prominent in the standard PDF-exposed group, mild in the low GDP bicarbonate/lactate-buffered group and absent in the other groups. Standard PDF induced accumulation of advanced glycation end products (AGEs) and up-regulation of the receptor for AGE (RAGE). AGEs accumulation was absent and RAGE expression was only modestly increased in low-GDP bicarbonate/lactate-buffered and amino acid-based PDF.


CONCLUSIONS
Long-term in vivo exposure to standard PDF adversely affects peritoneal function and structure. A low-GDP bicarbonate/lactate-buffered and amino acid-based PDF better preserved peritoneal integrity and may thus improve the longevity of the peritoneal membrane. GDPs and associated accelerated AGE formation are the main causative factors in PDF-induced peritoneal damage.
Mortier
Siska
S
Renal Unit, University Hospital, Ghent, Belgium. Siska.Mortier@Ugent.be
Faict
Dirk
D
Schalkwijk
Casper G
CG
Lameire
Norbert H
NH
De Vriese
An S
AS
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002021:Buffers; D015314:Dialysis Solutions / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010538:Peritonitis / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D001639:Bicarbonates; D002021:Buffers; D015314:Dialysis Solutions; D017127:Glycation End Products, Advanced; D007773:Lactates; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D005947:Glucose