The partial nitritation and anammox (PN/A) process has gained popularity for the treatment of nitrogen removal in wastewater due to significant energy savings and its potentially much lower CO2 footprint. However, the treatment of mainstream municipal wastewater by PN/A has been limited mainly due to its unsuitable composition. In this research, we apply ion exchange using a zeolite column to selectively remove and concentrate ammonium from mainstream municipal wastewater. After an absorption phase, the ion exchange column is regenerated using a brine solution. The ammonium rich brine is “bioregenerated” in a PN/A reactor where ammonium is converted to nitrogen gas allowing the brine to be reused in another cycle of ion exchange regeneration. To successfully remove ammonium from the spent brine, anammox and ammonia oxidizing bacteria (AOB) were first cultivated in separate reactors under hypersaline conditions (4.0 %) and later combined in a single PN/A reactor. After continuous operation with sea water, the PN/A reactor treated recirculating brine from the ion exchange column for 48 cycles of ammonium absorption and bioregeneration with minimal blowdown. The various cations of the regenerant solution were stable except for calcium that reached very high values upwards of 3000 mg/L as Ca2+ and finally caused PN/A reactor failure due to mineral precipitation. The buildup of high concentrations of calcium in the regenerant was addressed in two ways: 1) 20 % regenerant replacement per cycle, and 2) precipitation of CaCO3 via the addition of sodium carbonate. Both methods were applied to 30 absorption and bioregeneration cycles each and shown to be effective in keeping calcium concentrations from accumulating in the regenerant allowing for stable PN/A reactor operation.