title: Chronic uremia induces permeability changes, increased nitric oxide synthase expression, and structural modifications in the peritoneum.
abstract: Advanced glycation end products (AGE), growth factors, and nitric oxide contribute to alterations of the peritoneum during peritoneal dialysis (PD). These mediators are also involved in chronic uremia, a condition associated with increased permeability of serosal membranes. It is unknown whether chronic uremia per se modifies the peritoneum before PD initiation. A rat model of subtotal nephrectomy was used to measure peritoneal permeability after 3, 6, and 9 wk, in parallel with peritoneal nitric oxide synthase (NOS) isoform expression and activity and structural changes. Uremic rats were characterized by a higher peritoneal permeability for small solutes and an increased NOS activity due to the up-regulation of endothelial and neuronal NOS. The permeability changes and increased NOS activities correlated with the degree of renal failure. Focal areas of vascular proliferation and fibrosis were detected in uremic rats, in relation with a transient up-regulation of vascular endothelial growth factor and basic fibroblast growth factor, as well as vascular deposits of the AGE carboxymethyllysine and pentosidine. Correction of anemia with erythropoietin did not prevent the permeability or structural changes in uremic rats. Thus, in this rat model, uremia induces permeability and structural changes in the peritoneum, in parallel with AGE deposits and up-regulation of specific NOS isoforms and growth factors. These data suggest an independent contribution of uremia in the peritoneal changes during PD and offer a paradigm to better understand the modifications of serosal membranes in uremia.
authors.affiliation: Department of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium.|Department of Cell Biology, CEA, Saclay, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Combet
authors.affiliation: Department of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Ferrier
authors.affiliation: Department of Nephrology, Rijksuniversiteit Gent, Gent, Belgium.
authors.forename: Mieke VAN
authors.initials: MV
authors.lastname: Landschoot
authors.affiliation: Department of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium.
authors.forename: Maria
authors.initials: M
authors.lastname: Stoenoiu
authors.affiliation: Department of Pathology, Université Catholique de Louvain Medical School, Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Moulin
authors.affiliation: Institute of Medical Science and Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyata
authors.affiliation: Department of Nephrology, Rijksuniversiteit Gent, Gent, Belgium.
authors.forename: Norbert
authors.initials: N
authors.lastname: Lameire
authors.affiliation: Department of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
mesh_terms: D000740:Anemia / Q000188:drug therapy / Q000209:etiology; D000818:Animals; D002908:Chronic Disease; D003401:Creatine / Q000097:blood; D004921:Erythropoietin / Q000627:therapeutic use; D006133:Growth Substances / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000097:blood; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D010537:Peritoneum / Q000378:metabolism* / Q000473:pathology*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014508:Urea / Q000097:blood; D014511:Uremia / Q000097:blood / Q000378:metabolism* / Q000473:pathology*
chemical_list: D006133:Growth Substances; D004921:Erythropoietin; D014508:Urea; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat; D003401:Creatine