Drug Crystal-Related Gastrointestinal Complications Involve Crystal-Induced Release of Neutrophil and Monocyte Extracellular Traps
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 pathophysiolog...
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MDPI AG
2020-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/11/2481 |
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| author | Tehyung Kim Sueli de Oliveira Silva Lautenschlager Qiuyue Ma Kathrin Eller Marion Julia Pollheimer Danielle Lazarin-Bidóia Celso Vataru Nakamura Hans-Joachim Anders Stefanie Steiger |
| author_facet | Tehyung Kim Sueli de Oliveira Silva Lautenschlager Qiuyue Ma Kathrin Eller Marion Julia Pollheimer Danielle Lazarin-Bidóia Celso Vataru Nakamura Hans-Joachim Anders Stefanie Steiger |
| author_sort | Tehyung Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T14:51:04Z |
| format | Article |
| id | doaj.art-a955d37acdce4afcbef7058e11c0be45 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T14:51:04Z |
| publishDate | 2020-11-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-a955d37acdce4afcbef7058e11c0be452023-11-20T21:01:55ZengMDPI AGCells2073-44092020-11-01911248110.3390/cells9112481Drug Crystal-Related Gastrointestinal Complications Involve Crystal-Induced Release of Neutrophil and Monocyte Extracellular TrapsTehyung Kim0Sueli de Oliveira Silva Lautenschlager1Qiuyue Ma2Kathrin Eller3Marion Julia Pollheimer4Danielle Lazarin-Bidóia5Celso Vataru Nakamura6Hans-Joachim Anders7Stefanie Steiger8Division of Nephrology, Department of Medicine IV, Ludwig-Maximilians-University Hospital Munich, 80336 Munich, GermanyPostgraduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Paraná 5790, BrazilDivision of Nephrology, Department of Medicine IV, Ludwig-Maximilians-University Hospital Munich, 80336 Munich, GermanyDivision of Nephrology, Department of Internal Medicine, Medical University Graz, 8036 Graz, AustriaDiagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, AustriaPostgraduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Paraná 5790, BrazilPostgraduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Paraná 5790, BrazilDivision of Nephrology, Department of Medicine IV, Ludwig-Maximilians-University Hospital Munich, 80336 Munich, GermanyDivision of Nephrology, Department of Medicine IV, Ludwig-Maximilians-University Hospital Munich, 80336 Munich, GermanyIon-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.https://www.mdpi.com/2073-4409/9/11/2481sevelamerpolystyrene sulfonatecholestyraminepatiromerexchange resinextracellular traps |
| spellingShingle | Tehyung Kim Sueli de Oliveira Silva Lautenschlager Qiuyue Ma Kathrin Eller Marion Julia Pollheimer Danielle Lazarin-Bidóia Celso Vataru Nakamura Hans-Joachim Anders Stefanie Steiger Drug Crystal-Related Gastrointestinal Complications Involve Crystal-Induced Release of Neutrophil and Monocyte Extracellular Traps Cells sevelamer polystyrene sulfonate cholestyramine patiromer exchange resin extracellular traps |
| title | Drug Crystal-Related Gastrointestinal Complications Involve Crystal-Induced Release of Neutrophil and Monocyte Extracellular Traps |
| title_full | Drug Crystal-Related Gastrointestinal Complications Involve Crystal-Induced Release of Neutrophil and Monocyte Extracellular Traps |
| title_fullStr | Drug Crystal-Related Gastrointestinal Complications Involve Crystal-Induced Release of Neutrophil and Monocyte Extracellular Traps |
| title_full_unstemmed | Drug Crystal-Related Gastrointestinal Complications Involve Crystal-Induced Release of Neutrophil and Monocyte Extracellular Traps |
| title_short | Drug Crystal-Related Gastrointestinal Complications Involve Crystal-Induced Release of Neutrophil and Monocyte Extracellular Traps |
| title_sort | drug crystal related gastrointestinal complications involve crystal induced release of neutrophil and monocyte extracellular traps |
| topic | sevelamer polystyrene sulfonate cholestyramine patiromer exchange resin extracellular traps |
| url | https://www.mdpi.com/2073-4409/9/11/2481 |
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