1] Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland [2] Division of Nephrology, Université catholique de Louvain Medical School, Brussels, Belgium.
Department of Nephrology, Lund University, Lund, Sweden.
Kidney Int. 2014 Apr;85(4):750-8. doi: 10.1038/ki.2013.250. Epub 2013 Jun 26.
Peritoneal dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. The capillary endothelium offers the rate-limiting hindrance for solute and water transport. It can be functionally described in terms of a three-pore model including transcellular, ultrasmall pores responsible for free-water transport during crystalloid osmosis. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore located in endothelial cells. Studies in Aqp1 mice have shown that deletion of AQP1 is reflected by a 50% decrease in ultrafiltration and a disappearance of the sodium sieving. Haploinsufficiency in AQP1 is also reflected by a significant attenuation of water transport. Conversely, studies in a rat model and in PD patients have shown that the induction of AQP1 in peritoneal capillaries by corticosteroids is reflected by increased water transport and ultrafiltration, without affecting the osmotic gradient and small-solute transport. Recent data have demonstrated that a novel agonist of AQP1, predicted to stabilize the open-state conformation of the channel, modulates water transport and improves ultrafiltration. Whether increasing the expression of AQP1 or gating the already existing channels would be clinically useful in PD patients remains to be investigated.
腹膜透析涉及扩散和对流传输以及通过高度血管化的腹膜膜的渗透。毛细血管内皮细胞为溶质和水的传输提供了限速障碍。它可以根据三孔模型来进行功能描述，包括跨细胞和超小孔，这些孔负责晶体渗透期间自由水的传输。有几条证据表明，水通道蛋白 aquaporin-1 (AQP1) 对应于位于内皮细胞中的超小孔。在 Aqp1 小鼠中的研究表明，AQP1 的缺失反映在超滤减少 50%和钠离子筛除消失。AQP1 的单倍不足也反映在水传输的显著减弱。相反，在大鼠模型和 PD 患者中的研究表明，皮质类固醇诱导腹膜毛细血管中的 AQP1 表达增加，水传输和超滤增加，而不影响渗透梯度和小溶质的传输。最近的数据表明，AQP1 的一种新型激动剂，预测可以稳定通道的开放构象，调节水传输并改善超滤。增加 AQP1 的表达或打开已经存在的通道是否对 PD 患者具有临床意义仍有待研究。
