Moving toward a better understanding of renal lymphatics: challenges and opportunities

The development of lymphatic-specific markers has enabled detailed visualization of the lymphatic vascular network that has greatly enhanced our ability to explore this often-overlooked system. Lymphatics remove fluid, solutes, macromolecules, and cells from the interstitium and return them to circulation. The kidneys have lymphatics. As in other organs, the kidney lymphatic vessels are highly sensitive to changes in the local microenvironment. The sensitivity to its milieu may be especially relevant in kidneys because they are central in regulating fluid homeostasis and clearance of metabolites delivered into and eliminated from the renal interstitial compartment. Numerous physiologic conditions and diseases modify the renal interstitial volume, pressure, and composition that can, in turn, influence the growth and function of the renal lymphatics. The impact of the renal microenvironment is further heightened by the fact that kidneys are encapsulated. This review considers the development, structure, and function of the renal lymphatic vessels and explores how factors within the kidney interstitial compartment modify their structure and functionality. Moreover, although currently there are no pharmaceutical agents that specifically target the lymphatic network, we highlight several medications currently used in children with kidney disease and hypertension that have significant but underappreciated effects on lymphatics.