Endothelium structure and function in kidney health and disease

Abstract

The kidney harbours different types of endothelia, each with specific structural and functional characteristics. The glomerular endothelium, which is highly fenestrated and covered by a rich glycocalyx, participates in the sieving properties of the glomerular filtration barrier and in the maintenance of podocyte structure. The microvascular endothelium in peritubular capillaries, which is also fenestrated, transports reabsorbed components and participates in epithelial cell function. The endothelium of large and small vessels supports the renal vasculature. These renal endothelia are protected by regulators of thrombosis, inflammation and complement, but endothelial injury (for example, induced by toxins, antibodies, immune cells or inflammatory cytokines) or defects in factors that provide endothelial protection (for example, regulators of complement or angiogenesis) can lead to acute or chronic renal injury. Moreover, renal endothelial cells can transition towards a mesenchymal phenotype, favouring renal fibrosis and the development of chronic kidney disease. Thus, the renal endothelium is both a target and a driver of kidney and systemic cardiovascular complications. Emerging therapeutic strategies that target the renal endothelium may lead to improved outcomes for both rare and common renal diseases.

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Key points

The kidney contains diverse populations of endothelial cells, including the glomerular endothelium, microvascular endothelium in peritubular capillaries and the endothelium of large and small vessels, and each of these populations has specific characteristics and functions.

Homeostasis of renal endothelial cells is crucial for the preservation of glomerular structure and function, the preservation of an anti-inflammatory and an antithrombotic environment and the prevention of renal fibrosis.

Glomerular endothelial cells, in particular, are susceptible to injury in typical and atypical haemolytic uraemic syndrome, lupus nephritis, antineutrophil cytoplasmic antibody vasculitides and antibody-mediated rejection as well as in situations of vascular endothelial growth factor (VEGF) depletion.

Common forms of chronic kidney disease (CKD) — diabetic kidney disease and arteriolar nephrosclerosis — are also characterized by renal endothelial dysfunction.

Alterations in endothelial repair capacity, endothelial-to-mesenchymal transition and capillary rarefaction contribute to the fibrogenic processes that lead to CKD.

Therapeutic strategies aimed at preserving and/or restoring the integrity of the endothelial glycocalyx, reversing the procoagulant and pro-inflammatory phenotype of injured endothelial cells and slowing renal fibrosis hold promise for the treatment of renal disease.