A dual-stage system and methods for using the same include first and second filtration cartridges is provided and is particularly suited for hemodiafiltration and/or hemodialysis. As fluid enters the first filtration cartridge, the hydroxyl ion concentration and hence pH is increased by exposing it to either a strong base or a salt of a weak acid across a filter membrane. This stage allows for improved removal of certain toxins in the fluid, such as protein-bound substances that disassociate more readily from proteins at higher pH. As the filtered fluid enters the second filtration cartridge, the pH of the fluid is restored to normal levels prior to infusion to a patient.