A common gene variant for the protein Aquaporin-1 lowers the amount of water channels in the cell membranes. This reduces water transport and leads to a higher risk of death in patients with kidney failure treated with peritoneal dialysis. In such cases, specific osmotic solutions should be used, as an international research team led by the University of Zurich has shown.
Every day, the human kidneys clean about 1,500 liters of blood by producing approximately 1-2 liters of urine. Thereby, the body gets rid of excess water and toxic waste products of the metabolism or also drugs and maintains the balance of water and minerals in the tissues. While waiting for kidney transplantation, patients with chronic kidney failure must be treated regularly with dialysis that cleanses the body of fluid and deleterious substances. Peritoneal dialysis, which can be done at home with only minimal medical and technical support, is gaining popularity across the world. Today, kidney failure is a growing medical concern, concerning up to 10% of individuals globally.
Common variant of water transporter gene increases risk of deathAn international research team led by the University of Zurich (UZH) has now identified a common variant in the AQP1 gene coding for the water channel called Aquaporin-1 that has a significant effect on treatment efficacy and patient survival on dialysis. "The identification of this common genetic factor regulating the expression of Aquaporin-1, which is associated with a higher risk of death and technique failure, provides a big step for precision medicine in dialysis," says study coordinator and last author Olivier Devuyst from the UZH Department of Physiology. "The gene variant is driving the outcome of peritoneal dialysis and the choice of treatment modalities, which is very important for the care and outcome of patients with kidney failure," he adds.
The efficiency of dialysis depends on how well it removes excess of water, restores normal body fluid status, and clears waste substances. Peritoneal dialysis is based on osmosis: the introduction of an osmotic solution in the peritoneal cavity drives water transport preferentially through the Aquaporin-1 channels, which constitute the body's plumbing system. Previous studies by Devuyst' group showed that Aquaporin-1 is abundant in endothelial cells lining capillaries of the peritoneum, where it mediates fast osmotic water transport across cell membranes and up to half of the water removal during dialysis, a process named ultrafiltration.