A dialysate regeneration system for removing contaminants from spent dialysate according to this invention includes a dialysate circulation flow path including a pump that pumps spent dialysate through the dialysate circulation flow path, a first cartridge adapted to remove contaminants from the spent dialysate, including a first cleaning solution inlet and a first cleaning solution outlet, a second cartridge adapted to remove urea from the spent dialysate, the second cartridge including semi-permeable hollow fibers adapted for transport of urea across the walls of the semi-permeable hollow fibers and adapted to retain at least calcium, magnesium, and sodium ions in the spent dialysate, and including a second cleaning solution inlet and a second cleaning solution outlet. Ancillary to the two cartridges, the dialysate regeneration system further includes a first dialysate cleaning flow path including a pump that pumps first cleaning solution from the first cleaning solution outlet of the first cartridge through a first cleaning stage to the first cleaning solution inlet of the first cartridge, and a second dialysate cleaning flow path including a pump that pumps second cleaning solution from the second cleaning solution outlet of the second cartridge through a second cleaning stage to the second cleaning solution inlet of the second cartridge.