Introduction: Hyperkalemia, although a common electrolyte abnormality, poses a grave danger in causing cardiac arrhythmias and possibly death if not corrected. Sodium polystyrene sulfonate (Kayexalate) plays a role in the excretion of potassium from the gastrointestinal tract. Since its approval in 1958, Kayexalate's efficacy has been debatable and very few cases of colonic and ileal necrosis were reported. We report a case of an 80-year-old female with hyperkalemia who was treated with Kayexalate and developed colonic ischemia. Case: An 80-year-old -female with chronic kidney disease stage V and coronary artery disease presented for worsening bilateral lower extremity swelling and decreased exercise tolerance. Patient was admitted for congestive heart failure exacerbation. During the stay, she developed hyperkalemia with potassium of 6.6 mmol/L for which she was managed with oral Kayexalate. Subsequently, the patient complained of abdominal pain with bright red blood in the stool. Vitals were normal. On physical examination, abdomen was distended, and diffusely tender with guarding. Laboratory results showed white cell count of 29.4 K/cmm, hemoglobin 8.9 gm/dl and lactic acid of 3.8. Computed tomography (CT) scan of abdomen and pelvis demonstrated wall thickening, pneumatosis coli and adjacent fat stranding at the transverse colon [Figure 1]. Colonoscopy revealed lumen obstructing clot in the mid transverse colon with adjacent unhealthy mucosa which which was bleeding upon contact. Scope could not be advanced safely past the large clot [Figure 2]. Patient was managed conservatively with significant improvement eventually.Figure: CT revealing wall thickening and pneumatosis coli at the distal ascending to proximal transverse colon (red arrow).Figure: Colonoscopy showing signs of active bleeding in the transverse colon.Discussion: Sodium polystyrene sulfate is a cation exchange resin, given orally or as an enema for treatment of hyperkalemia. Kayexalate induced colonic necrosis may occur as early as a few hours to many days after administration. Patients present with complaints of abdominal pain, nausea, diarrhea and/or rectal bleeding. The diagnosis is often confirmed with colonoscopy and histopathology of biopsy specimen. Histology may show angulated crystals of sodium polystyrene sulfate in segments of mucosal erosions, ulcerations or necrosis. In conclusion, with increasing numbers of patients with end stage kidney disease, hyperkalemia remains an ever common condition encountered by clinicians. Therefore, clinicians must maintain a low threshold of suspicion for the rare but dire complication of colonic necrosis induced by kayexalate.