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Intestinal Lymphatic Dysfunction in Kidney Disease

Journal

CIRCULATION RESEARCH
Volume 132, Issue 9, Pages 1226-1245

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.122.321671

Keywords

intestines; kidney; lymphatic; renal insufficiency; chronic

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Kidney disease has adverse effects on various organs beyond the kidney, such as the heart, lungs, brain, and intestines. Recent studies show that kidney injury affects the intestinal lymphatics, leading to harmful substance production and distribution, which contributes to disease progression in distant organs. Understanding the mechanisms of kidney-intestinal cross talk is important for comprehending the vicious cycle of organ damage and developing new therapeutic strategies.
Kidney disease is associated with adverse consequences in many organs beyond the kidney, including the heart, lungs, brain, and intestines. The kidney-intestinal cross talk involves intestinal epithelial damage, dysbiosis, and generation of uremic toxins. Recent studies reveal that kidney injury expands the intestinal lymphatics, increases lymphatic flow, and alters the composition of mesenteric lymph. The intestinal lymphatics, like blood vessels, are a route for transporting potentially harmful substances generated by the intestines. The lymphatic architecture and actions are uniquely suited to take up and transport large macromolecules, functions that differentiate them from blood vessels, allowing them to play a distinct role in a variety of physiological and pathological processes. Here, we focus on the mechanisms by which kidney diseases result in deleterious changes in intestinal lymphatics and consider a novel paradigm of a vicious cycle of detrimental organ cross talk. This concept involves kidney injury-induced modulation of intestinal lymphatics that promotes production and distribution of harmful factors, which in turn contributes to disease progression in distant organ systems.

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