Toward better dialysis compatibility: Advances in the biochemistry and pathophysiology of the peritoneal membranes

Peritoneal dialysis (PD) has modified our concept of the peritoneal membrane, which is now a topic of active research. Peritoneal solute transport progressively increases with time on PD, enhances the dissipation of the osmotic gradient and, eventually, reduces ultrafiltration capacity. The causes of peritoneal membrane failure remain elusive. Recurrent episodes of peritonitis are not a prerequisite for the development of ultrafiltration failure. 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 information 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. This review focuses on reactive carbonyls and their association with a number of molecular changes observed in peritoneal tissues. This hypothetical approach will require further testing. Nevertheless, the insights gained on the peritoneal membrane offer a new paradigm to assess the effect of uremic toxins on serosal membranes. Furthermore, the progresses made in the dissection of the molecular events leading to peritoneal membrane failure open new avenues to develop safe, more biocompatible peritoneal dialysis technologies.