| Research Abstract |
Peritoneal solute transport progressively increases with time on PD, enhances the dissipation of the osmotic gradient, and eventually reduces ultrafiltration capacity. Functionally, the changes of the failing peritoneal membrane are best described as an increased functional area of exchange for small solutes between blood and dialysate. Histologically, these events are associated with vascular proliferation and structural changes of pre-existing vessels. Gathered evidence, including informations on the composition of peritoneal cavity fluids and its dependence on the uremic environment, have cast a new light on the molecular mechanisms of decline in peritoneal membrane function. Chronic uremia per se modifies the peritoneal membrane and increases the functional area of exchange for small solutes. Biochemical alterations in the peritoneum inherent to uremia might be, at least in part, accounted for by severe reactive carbonyl compounds overload originating both from uremic circulation and PD fluid ("peritoneal carbonyl, stress"). The molecular events associated with long-term PD are similar but more severe than those present in chronic uremia without PD, including modifications of nitric oxide synthase (NOS) and angiogenic growth factors expression, and advanced glycation and lipoxidation of the peritoneal proteins. Furthermore, the progresses made in the dissection of the molecular events leading to peritoneal membrane failure open new avenues to develop a safe, more biocompatible peritoneal dialysis technologies, i.e., the glyoxalase detoxification system and RCO trapping bead.
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