Abstract
Ion-exchange resins are commonly used to manage complications of chronic kidney disease, such as hyperphosphatemia, hyperkalemia, and hypercholesterolemia. Occasionally, these drugs can irritate the gastrointestinal lining and cause life-threatening intestinal necrosis. Currently, the pathophysiology of drug crystal-induced intestinal necrosis is not well understood. We hypothesized that crystals of ion-exchange resins like sevelamer, polystyrene sulfonate, and cholestyramine can trigger the formation of neutrophil and monocyte extracellular traps by contributing to intestinal barrier dysfunction. Light and fluorescence microscopy of the colonic resection specimen from a patient with chronic kidney disease revealed severe intestinal necrosis, ulceration, sevelamer crystals, and inflammation upon oral intake of sevelamer, as well as the formation of neutrophil extracellular traps in proximity to small sevelamer crystals. Indeed, drug crystals reduced metabolic activity and induced barrier dysfunction and cell death in human intestinal epithelial cells in vitro. In addition, drug crystals triggered the release of neutrophil and monocyte extracellular traps. Taken together, these data raise the possibility that besides other factors including chronic kidney disease, diabetes mellitus, and hypertension, drug crystals may further amplify a pre-existing barrier dysfunction and necroinflammation in a crescendo of local intestinal necrosis and systemic inflammation/infection, as occasionally observed in patients on ion-exchange resin therapy.
Highlights
Oral intake of ion-exchange resins is clinically used to prevent certain dietary components from absorption in the intestinal tract
We describe a case of sevelamer crystal-associated intestinal necrosis
We hypothesized that crystals of sevelamer, polystyrene sulfonate, and cholestyramine can trigger the formation of neutrophil extracellular trap (NET) and macrophage extracellular traps (METs), a process that contributes to intestinal barrier dysfunction and necrosis
Summary
Oral intake of ion-exchange resins is clinically used to prevent certain dietary components from absorption in the intestinal tract. The anion-exchange resins sevelamer and cholestyramine are used to trap phosphate and bile and the cation-exchange resins polystyrene sulfonate and patiromer are used to trap potassium. Such ion-exchange resins are usually well tolerated, they are. Cells 2020, 9, 2481 occasionally associated with life-threatening intestinal necrosis [1]. Such patients experience a sudden onset of abdominal pain, rectal bleeding, diarrhea, and hematochezia, which can progress to overt peritonitis, sepsis, and multiorgan failure. The role of ion-exchange resins in these complications is unknown
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