Adverse reactions during hemodialysis are extremely common and include a wide range of clinical presentations from mild to life threatening. We present a case of a 34 year old woman in the Burn Intensive Care Unit, who developed acute kidney injury requiring renal replacement therapy. She was placed on continuous veno-venous hemofiltration with the NxStage machine which uses a synthetic PUREMA polyethersulfone filter sterilized by gamma radiation. Within two minutes of initiating hemofiltration, the patient complained of pruritus as well as dyspnea and became flushed and agitated. She subsequently developed hypotension ultimately resulting in cardiopulmonary arrest. Cardiopulmonary resuscitation was initiated and the patient was given epinephrine with return of spontaneous circulation. The following day, the patient was rechallenged with a PUREMA filter, and had a similar reaction with flushing, dyspnea, pruritus and hypotension requiring treatment to be discontinued. The patient was transitioned to the Prismaflex filter, another synthetic membrane, which she tolerated well and continued to utilize through the remainder of her hospital course without complication. Her clinical presentation was consistent with an anaphylactoid reaction, though a tryptase level was not obtained and a radioallergosorbent test performed with membrane material was negative. This case shows the difficulty of identifying the cause of hypersensitivity reactions involving synthetic membranes not sterilized by ethylene oxide, a commonly use sterilizing agent known to cause hypersensitivity reactions. This rare, but potentially fatal reaction has not previously been reported with a PUREMA filter and this case should raise awareness of hypersensitivity reactions with this widely used method of renal replacement therapy.