Phosphate capture enhancement in peritoneal dialysis process using designed recyclable iron oxide nanostructures – PHODIA

In patients suffering of chronic kidney disease (CKD), phosphates accumulation in blood is very dangerous and dialysis is the only way to remove them from blood, for those waiting for transplantation. Phosphate imbalance leads to a high cardiovascular mortality and to bone disorder in dialysis patients. Current procedures (hemodialysis (HM) and peritoneal dialysis (PD)) do not allow for the removal of sufficient phosphate amounts, as does normal kidney function. HD consists of extracorporeal blood purification with the help of a machine. During PD procedure, a designed dialysis solution is introduced into the peritoneal cavity of the patient and for a few hours, the composition of the liquid is balanced with that of the blood compartment. By diffusion and convection mechanisms through the capillaries, toxins and water in excess pass into the dialysate. The dialysate is then drained outside the body before the subsequent provision of new dialysate. The duration of the exchanges varies according to the needs of the patient.
PHODIA project proposes to investigate the addition of iron oxide nanoparticles (IONPs) into dialysate used for PD to enhance phosphate removal from blood and possibly reduce the duration of PD for patients. It would allow establishing PD as the most adapted dialysis method. Indeed, in addition to being cheaper than HD, PD has many advantages for the patient: the possibility of being autonomous in the treatment, fewer hospital admissions needed (and therefore reduced transport costs), fewer secondary treatments such as anticoagulants, and the possibility of carrying out the treatment during the night. It allows for less diet and fluid restriction for the patient and a better vascular preservation compared to HD. This last point makes that PD is mainly used for infants and newborn babies.
Therefore, the increase in phosphate removal efficiency by introducing IONPs in the dialysate would allow a very large number of patients to benefit from this more comfortable and less expensive PD technique. Such solution using IONPs for improving phosphate removal by PD was never tested before and is thus proposed for the first time.
The first objective will be to synthesize IONPs with size and surface specific area optimized to ensure a good colloidal stability in dialysate, no transfer of IONPs from dialysis solution to blood vessels and a high phosphate capture. Three different IONPs synthesis methods and in particular one method leading to mesoporous IONPs, will be tested to screen IONPs with different mean diameter, pore size and surface specific area.
We will then study the adsorption of phosphate of designed IONPs. We will pay attention to the possibility of IONPs removing other toxins and will verify that essential compounds will not be removed during the PD process.
Another original objective is the building of an in vitro set-up mimicking the PD treatment to test and optimize IONPs design and extraction. It will aim at reproducing as closely as possible the exchanges that take place through the peritoneum during a dialysis session, as well as the conditions of exchange and at allowing feasibility tests without immediate recourse to animals trials. Chelating agent of 99mTc will be coupled at the surface of IONPs to follow their diffusion in the PD set-up by nuclear imaging with a gamma camera.
Finally, we will check, by in vitro experiments, the interactions of IONPs with cells of peritoneal membrane and study their in vivo fate in dialysate and rats by nuclear imaging.
The ultimate goal is to formulate dialysates containing a minimal and controlled amount of IONPs to extract a higher and controlled amount of phosphates during a PD procedure and possibly to reduce the duration of the PD treatment. This project would establish PD as an efficient procedure for controlling CKD and increase its use for better comfort in adult patients and better effectiveness in children, for whom it is the only possible treatment.