What is it about?

Kidney failure causes accumulation of waste products and fluid overload. Peritoneal dialysis removes excess of body fluids by high amounts of glucose that are present in the dialysis solution in the belly, because glucose induces osmosis, meaning that it removes water from the reminder of body to the belly. The saturated fluid is regularly drained and replaced by a fresh dialysis solution. The major part of the glucose is removed this way, but some is taken up in peritoneal tissue. Impairment of fluid removal also called ultrafiltration failure, can develop in patients on long-term peritoneal dialysis. The current review encompasses the possible causes and includes a hypothesis on the underlying mechanisms. The continuous exposure and uptake of peritoneal tissue to the required extremely high glucose concentrations in the dialysis solutions is the central issue in this so called glucose/hypoxia/GLUT-1 hypothesis. At the cellular level glucose exposure causes a situation of oxygen shortage, similar to what happens in diabetes mellitus. This pseudohypoxia induces various factors, among which are some that stimulate the formation of fibrous tissues and also of some glucose transporters, that are proteins stimulating the uptake of glucose into cells. Fibrous cells express the glucose transporter GLUT-1. Consequently a vicious circle develops between uptake of glucose in the dialysis solution into peritoneal fibrous cells, leading to more cells and further increased glucose uptake by GLUT-1. The result is a reduction of the osmosis required for removal of excess fluid, so the development of ultrafiltration failure and consequently fluid overload.

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Why is it important?

The increase in the number of kidney failure patients treated with peritoneal dialysis augments the number of long-term PD complications, of which impaired ultrafiltration is an important one , because it often causes fluid overload, which is associated with increased mortality. This review highlights what is known about the causes and contains a hypothesis on the possible underlying pathophysiology. It speculates on strategies to avoid aquired ultrafiltration failure.

Perspectives

Having retired from clinical practice enabled me to think of a possible explanation for the development of ultrafiltration failure in long-term PD patients, a largely unexplained condition. This required studying basic science, for which I simply had no time during my clinical and educational duties. At the end the explanation was a rather simple vicious circle.

Raymond Krediet
Amsterdam University Mediclal Center

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This page is a summary of: Acquired Decline in Ultrafiltration in Peritoneal Dialysis: The Role of Glucose, Journal of the American Society of Nephrology, July 2021, American Society of Nephrology, DOI: 10.1681/asn.2021010080.
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