A dialysate regeneration system for removing contaminants from spent dialysate comprising: a) a dialysate circulation flow path including: i) a pump that pumps spent dialysate through the dialysate circulation flow path; ii) a first cartridge adapted to remove contaminants from the spent dialysate, including a first cleaning solution inlet and a first cleaning solution outlet; and iii) 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 dialysate, wherein the hollow fibers are fabricated from or coated with a cation-rejecting material, and including a second cleaning solution inlet and a second cleaning solution outlet; b) a first dialysate cleaning flow path including a pump that pumps first cleaning solution from the first cleaning solution inlet of the first cartridge through a first cleaning stage to the first cleaning solution outlet of the first cartridge; and c) a second dialysate cleaning flow path including a pump that pumps second cleaning solution from the second cleaning solution inlet of the second cartridge through a second cleaning stage to the second cleaning solution outlet of the second cartridge. a) a dialysate circulation flow path including: i) a pump that pumps spent dialysate through the dialysate circulation flow path; ii) a first cartridge adapted to remove contaminants from the spent dialysate, including a first cleaning solution inlet and a first cleaning solution outlet; and iii) 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 dialysate, wherein the hollow fibers are fabricated from or coated with a cation-rejecting material, and including a second cleaning solution inlet and a second cleaning solution outlet; i) a pump that pumps spent dialysate through the dialysate circulation flow path; ii) a first cartridge adapted to remove contaminants from the spent dialysate, including a first cleaning solution inlet and a first cleaning solution outlet; and iii) 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 dialysate, wherein the hollow fibers are fabricated from or coated with a cation-rejecting material, and including a second cleaning solution inlet and a second cleaning solution outlet; b) a first dialysate cleaning flow path including a pump that pumps first cleaning solution from the first cleaning solution inlet of the first cartridge through a first cleaning stage to the first cleaning solution outlet of the first cartridge; and c) a second dialysate cleaning flow path including a pump that pumps second cleaning solution from the second cleaning solution inlet of the second cartridge through a second cleaning stage to the second cleaning solution outlet of the second cartridge.