Insights into glomerular function and disease pathogenesis

More than three-quarters of cases of chronic kidney disease are caused by glomerular diseases with glomerulosclerosis, including diabetic kidney disease, hypertensive nephropathy and glomerulonephritis. Studies in 2022 provided insights into the molecular mechanisms that maintain dynamic glomerular structures and the responses of specific glomerular cell types during glomerular disease.

Key advances

• Drosophila nephrocytes rely on rapid endocytosis and recycling of the fly orthologue of nephrin to maintain the structural integrity of the slit diaphragm².

• The slit diaphragm might act as a molecular sensor that regulates filtration barrier plasticity³.

• Adaptive remodelling of the ventral actin cytoskeleton and integrin adhesion complexes to maintain podocyte attachment to the glomerular basement membrane is dependent on the actin-binding protein α-parvin⁴.

• The histone deacetylase inhibitor panobinostat promotes differentiation of progenitor parietal epithelial cells to podocytes and has renoprotective effects in experimental crescentic glomerulonephritis⁵.

• In a mouse model of early IgA nephropathy, changes in glomerular endothelial cells that promote the recruitment and infiltration of immune cells precede pathogenic transcriptional activation in mesangial cells and podocytes⁶.