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

腹膜溶质转运随着腹膜透析时间的延长而逐渐增加，增强了渗透梯度的消散，并最终降低了超滤能力。在功能上，失效腹膜的变化最好描述为血液和透析液之间小溶质交换的功能面积增加。在组织学上，这些事件与血管增殖和既存血管的结构变化相关。收集到的证据，包括腹膜腔液体的组成及其对尿毒症环境的依赖性的信息，为腹膜功能下降的分子机制提供了新的线索。慢性尿毒症本身改变了腹膜，增加了交换小分子溶质的功能面积。尿毒症固有的腹膜生化改变可能至少部分是由于尿毒症循环和PD液（“腹膜羰基，应激”）引起的严重反应性羰基化合物过载。与长期PD相关的分子事件与慢性尿毒症无PD患者相似，但更严重，包括一氧化氮合酶（NOS）和血管生成生长因子表达的改变，以及腹膜蛋白的晚期糖基化和脂氧化。此外，在解剖导致腹膜衰竭的分子事件方面取得的进展为开发安全的、更生物相容的腹膜透析技术开辟了新的途径，即，草甘膦酶解毒系统和RCO捕获珠。

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.