Kidney lymphatics: new insights in development and disease

Abstract

This review will highlight recent advances in our understanding of the kidney lymphatics regarding their development, physiologic function, and their potential role in the progression of kidney disease. Although sparse in comparison to the blood vasculature, lymphatic vessels within the healthy kidney perform an important role in maintaining homeostasis. Additionally, in response to kidney injury, lymphatic vessels undergo substantial expansion, termed lymphangiogenesis, which shows a direct correlation to the extent of tubulointerstitial fibrosis. Kidney lymphatics expand through both the proliferation of lymphatic endothelial cells from existing lymphatic vessels, as well as from direct contribution by other cell types of nonvenous origin. The primary driver of lymphatic growth is vascular endothelial growth factor C, both in development and in response to injury. The clinical implications of lymphangiogenesis in the setting of kidney diseases remains debated, however growing evidence suggests lymphatic vessels may perform a protective role in clearing away accumulating interstitial fluid, inflammatory cytokines, and cellular infiltrates that occur with injury. There is increasing evidence the kidney lymphatics perform an active role in the response to kidney injury and the development of fibrosis. Recent advances in our understanding of these vessels raise the possibility of targeting kidney lymphatics for the treatment of kidney disease.