Answer: Ischemic colitis associated with kayexalate

Histology: The images show surface epithelial sloughing, and lamina propria fibrosis with crypt drop-out. There are few regenerative crypts at the base which appear hyperchromatic.
There are also crystalline, slightly basophilic/magenta appearing crystals which are mosaic-like or “fish-scaled”. These crystals are kayexalate.

Discussion: Kayexalate or sodium polystyrene sulfonate is a sodium potassium ion-exchange resin used to treat hyperkalemia, and is administered orally, via nasogastric tube or as an enema. Kayexalate binds intraluminal potassium in exchange for sodium. The excess potassium is then excreted in stool. Kayexalate can cause constipation and bowel obstruction due to fecal impaction as the resin binds to luminal calcium. Thus, Kayexalate is given with sorbitol which is a hypertonic solution and acts as a laxative. Administering Kayexalate with sorbitol can cause complications such as nausea, vomiting, electrolyte imbalance, and diarrhea. Uremic, especially post renal transplant patients and neonates are susceptible to bleeding due to ischaemic necrosis of the intestine and high mortality. Contributing factors may include hypovolemia after surgery or dialysis, infections, immunosuppression etc.

Intestinal necrosis caused by Kayexalate in sorbitol is a well known complication and was described first by Lillimoe et al. in 1987 who reported gastrointestinal bleeding in five uremic patients after receiving Kayexalate in sorbitol enemas. The incidence of intestinal necrosis is approximately 0.27% overall and 1.8% in postoperative patients. Kayexalate in sorbitol can induce damage in the upper as well as lower gastrointestinal tracts.

It is important to keep in mind that Kayexalate may be just an incidental finding in an otherwise unremarkable mucosal biopsy. However, it is also an underrecognized cause of ischaemic necrosis and may go unnoticed by both pathologists and clinicians. Although Kayexalate by itself causes no damage and is an innocent bystander, its presence should alert the pathologist of a possible casual relationship to sorbitol induced intestinal necrosis. Sorbitol cannot be identified in histological sections.

Kayexalate crystals need to be differentiated from cholestyramine crystals. Kayexalate crystals are basophilic with a characteristic mosaic (fish-scale) appearance on H & E stain, are red on acid-fast stain, and are refractile but not polarizable. Cholestyramine crystals are rhomboid and opaque on H & E stain, and are pink on acid-fast stain.

Reference(s):
Rashid A, Hamilton SR. Necrosis of the gastrointestinal tract in uremic patients as a result of sodium polystyrene sulfonate (Kayexalate) in sorbitol: an underrecognized condition. Am J Surg Pathol, 1997; 21:60-69.

Lillimoe KD, Romolo JL, Hamilton SR et al. Intestinal necrosis due to sodium polystyrene (Kayexalate) in sorbitol enemas:clinical and experimental support for the hypothesis. Surgery, 1987;101:267-72.