The potential role of complement alternative pathway activation in hypertensive renal damage

Abstract

Hypertensive renal damage is a common secondary kidney disease caused by poor control of blood pressure. Recent evidence has revealed abnormal activation of the complement alternative pathway (AP) in hypertensive patients and animal models and that this phenomenon is related to hypertensive renal damage. Conditions in the setting of hypertension, including high renin concentration, reduced binding of factor H to the glomerular basement membrane, and abnormal local synthesis of complement proteins, potentially promote the AP activation in the kidney. The products of the AP activation promote the phenotypic transition of mesangial cells and tubular cells, attack endothelial cells and recruit immunocytes to worsen hypertensive renal damage. The effects of complement inhibition on hypertensive renal damage are contradictory. Although clinical data support the use of C5 monoclonal antibody in malignant hypertension, pharmacological inhibition in hypertensive animals provides little benefit to kidney function. Therefore, the role of the complement AP in the pathogenesis of hypertensive renal damage and the value of complement inhibition in hypertensive renal damage treatment must be further explored.

Current perspectives and trends of the research on hypertensive nephropathy: a bibliometric analysis from 2000 to 2023

“…Moreover, the hemichannels (HC) and pannexons, which are critical channels for intracellular Ca 2+ signaling, have been explored their roles in the Ang II-mediated renal damage [ 27 ]. Additionally, the abnormal activation of the complement system [ 28 ] and ferroptosis [ 29 ] also contributed to the pathogenesis of HTN.…”