Acquired Decline in Ultrafiltration in Peritoneal Dialysis: The Role of Glucose

被引:35
作者
Krediet, Raymond T. [1 ]
机构
[1] Amsterdam Univ Med Ctr, Dept Med, Div Nephrol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2021年 / 32卷 / 10期
关键词
peritoneal dialysis; free water transport; small pore fluid transport; pseudohypoxia; ultrafiltration insufficiency; hypoxia; glucose transporters; myofibroblasts; osmolality; MESOTHELIAL CELLS; SOLUTE TRANSPORT; SGLT2; INHIBITION; FLUID TRANSPORT; WATER TRANSPORT; EXPRESSION; MEMBRANE; FAILURE; LONG; PROTEINS;
D O I
10.1681/ASN.2021010080
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Ultrafiltration is essential in peritoneal dialysis (PD) for maintenance of euvolemia, making ultrafiltration insufficiency?preferably called ultrafiltration failure?an important complication. The mechanisms of ultrafiltration and ultrafiltration failure are more complex than generally assumed, especially after long-term treatment. Initially, ultrafiltration failure is mainly explained by a large number of perfused peritoneal microvessels, leading to a rapid decline of the crystalloid osmotic gradient, thereby decreasing aquaporin-mediated free water transport. The contribution of peritoneal interstitial tissue to ultrafiltration failure is limited during the first few years of PD, but becomes more important in long-term PD due to the development of interstitial fibrosis, which mainly consists of myofibroblasts. A dual hypothesis has been developed to explain why the continuous exposure of peritoneal tissues to the extremely high dialysate glucose concentrations causes progressive ultrafiltration decline. First, glucose absorption causes an increase of the intracellular NADH/NAD(+) ratio, also called pseudohypoxia. Intracellular hypoxia stimulates myofibroblasts to produce profibrotic and angiogenetic factors, and the glucose transporter GLUT-1. Second, the increased GLUT-1 expression by myofibroblasts increases glucose uptake in these cells, leading to a reduction of the osmotic gradient for ultrafiltration. Reduction of peritoneal glucose exposure to prevent this vicious circle is essential for high-quality, long-term PD.
引用
收藏
页码:2408 / 2415
页数:8
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