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Chronic uremia induces permeability changes, increased nitric oxide synthase expression, and structural modifications
Sophie Combet1,2, Marie-Laure Ferrier1, Mieke VAN Landschoot3
1Department of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium.
Journal of the American Society of Nephrology : JASN
|September 20, 2001
Summary
Chronic kidney disease (CKD) alters the peritoneum before dialysis, increasing its permeability. Uremia causes structural changes and deposits, independent of anemia treatment.
Area of Science:
- Nephrology
- Pathology
- Physiology
Background:
- Peritoneal dialysis (PD) involves advanced glycation end products (AGE), growth factors, and nitric oxide (NO) affecting the peritoneum.
- These mediators are implicated in chronic uremia and increased serosal membrane permeability.
- The impact of chronic uremia on the peritoneum prior to PD initiation remains unclear.
Purpose of the Study:
- To investigate whether chronic uremia itself modifies peritoneal structure and permeability.
- To examine changes in peritoneal nitric oxide synthase (NOS) isoforms and growth factors in uremia.
- To assess the role of AGEs in uremia-induced peritoneal alterations.
Main Methods:
- A rat model of subtotal nephrectomy was employed to induce chronic uremia.
- Peritoneal permeability, NOS isoform expression and activity, and structural changes were assessed at 3, 6, and 9 weeks.
- Levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and AGEs (carboxymethyllysine, pentosidine) were analyzed.
Main Results:
- Uremic rats exhibited increased peritoneal permeability to small solutes and elevated NOS activity due to upregulated endothelial and neuronal NOS.
- These changes correlated with the severity of renal failure.
- Focal vascular proliferation and fibrosis were observed, linked to transient VEGF and bFGF upregulation and AGE deposition.
Conclusions:
- Uremia induces significant peritoneal permeability and structural changes, independent of anemia correction.
- AGE deposition and altered expression of NOS isoforms and growth factors contribute to uremia-induced peritoneal modifications.
- These findings suggest uremia plays a direct role in peritoneal alterations during PD, offering insights into serosal membrane changes in uremia.