Beelen, Robert H J

Celie, Johanna W A M

Keuning, Eelco D

Loureiro, Jesus

Schilte, Margot N

ter Wee, Piet M

van den Born, Jacob

BACKGROUND: Peritoneal dialysis (PD) is associated with functional and structural alterations of the peritoneal membrane, particularly new vessel formation and fibrosis. In addition to anticoagulant effects, heparin displays anti-inflammatory and angiostatic properties. Therefore, the effects of administration of heparins on function and morphology of the peritoneal membrane were studied in a rat PD model.METHODS: Rats received 10 mL conventional PD fluid (PDF) daily, with or without the addition of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) in the PDF (1 mg/10 mL intraperitoneally) via a mini access port. Untreated rats served as controls. After 5 weeks, a 90-minute functional peritoneal transport test was performed and tissues and peritoneal leukocytes were taken.RESULTS: PD treatment induced loss of ultrafiltration (p&lt;0.01), a twofold increase in glucose absorption (p&lt;0.03), increased urea transport (p&lt;0.02), and loss of sodium sieving (p&lt;0.03), which were also found in the PDF+heparin groups. Increased peritoneal cell influx and hyaluronan production (p&lt;0.02) as well as an exchange of mast cells and eosinophils for neutrophils after PD treatment were observed in PD rats; addition of heparin did not affect those changes. Mesothelial regeneration, submesothelial blood vessel and matrix formation, and accumulation of tissue macrophages were seen in PD animals. Spindle-shaped vimentin-positive and cytokeratin-negative cells indicated either partial injury and denudation of mesothelial cells or epithelial-to-mesenchymal transition. Neither UFH nor LMWH affected any of these morphological changes.CONCLUSION: Within 5 weeks, PD treatment induces a chronic inflammatory condition in the peritoneum, evidenced by high transport, leukocyte recruitment, tissue remodeling, and induction of spindle-shaped cells in the mesothelium. Addition of LMWH or UFH to the PDF did not prevent these adverse PDF-induced peritoneal changes.</p

Long-term intervention with heparins in a rat model of peritoneal dialysis

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