Chronic uremia induces permeability changes, increased nitric oxide synthase expression, and structural modifications in the peritoneum

Advanced glycation end products (AGE), growth factors, and nitric oxide con tribute to alterations of the peritoneum during peritoneal dialysis (PID). These mediators are also involved in chronic uremia. a condition associated with increased permeability of serosal membranes. It is unknown whether ch ronic uremia per se modifies the peritoneum before PD initiation. A rat mod el of subtotal nephrectomy was used to measure peritoneal permeability afte r 3, 6, and 9 wk, in parallel with peritoneal nitric oxide synthase (NOS) i soform expression and activity and structural changes. Uremic rats were cha racterized by a higher peritoneal permeability for small solutes and an inc reased NOS activity due to the up-regulation of endothelial and neuronal NO S. The permeability changes and increased NOS activities correlated with th e degree of renal failure. Focal areas of vascular proliferation and fibros is 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 indu ces 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 peritonea l changes during PD and offer a paradigm to better understand the modificat ions of serosal membranes in uremia.