Strategies for optimizing urea removal to enable portable kidney dialysis: A reappraisal

Background: Portable hemodialysis has the potential to improve health outcomes and quality of life for patients with kidney failure at reduced costs. Urea removal, required for dialysate regeneration, is a central function of any existing/potential portable dialysis device. Urea in the spent dialysate coexists with non-urea uremic toxins, nutrients, and electrolytes, all of which will interfere with the urea removal efficiency, regardless of whether the underlying urea removal mechanism is based on urease conversion, direct urea adsorption, or oxidation. The aim of the current review is to identify the amount of the most prevalent chemicals being removed during a single dialysis session and evaluate the potential benefits of an urea-selective membrane for portable dialysis. Methods: We have performed a literature search using Web of Science and PubMed databases to find available articles reporting (or be able to calculate from blood plasma concentration) > 5 mg of individually quantified solutes removed during thrice-weekly hemodialysis sessions. If multiple reports of the same solute were available, the reported values were averaged, and the geometric mean of standard deviations was taken. Further critical literature analysis of reported dialysate regeneration methods was performed using Web of Science and PubMed databases. Results: On average, 46.0 g uremic retention solutes are removed in a single conventional dialysis session, out of which urea is only 23.6 g. For both urease- and sorbent-based urea removal mechanisms, amino acids, with 7.7 g removal per session, could potentially interfere with urea removal efficiency. Additionally for the oxidation-based urea removal system, plentiful nutrients such as glucose (24.0 g) will interfere with urea removal by competition. Using a nanofiltration membrane between dialysate and oxidation unit with a molecular weight cutoff (MWCO) of similar to 200 Da, 67.6 g of non-electrolyte species will be removed in a single dialysis session, out of which 44.0 g are non-urea molecules. If the membrane MWCO is further decreased to 120 Da, the mass of non-electrolyte non-urea species will drop to 9.3 g. Reverse osmosis membranes have been shown to he both effective at blocking the transport of non-urea species (creatinine for example with similar to 90% rejection ratio), and permissive for urea transport (similar to 20% rejection ratio), making them a promising urea selective membrane to increase the efficiency of the oxidative urea removal system. Conclusions: Compiled are quantified solute removal amounts greater than 5 mg per session during conventional hemodialysis treatments, to act as a guide for portable dialysis system design. Analysis shows that multiple chemical species in the dialysate interfere with all proposed portable urea removal systems. This suggests the need for an additional protective dialysate loop coupled to urea removal system and an urea-selective membrane.