Vascular endothelial growth factor A (
VEGF-A) is a prominent pro-angiogenic and pro-permeability factor in the kidney. Alternative splicing of the terminal exon of
VEGF-A through the use of an alternative
3' splice site gives rise to a functionally different family of
isoforms, termed
VEGF-Axxxb, known to have anti-angiogenic and anti-permeability properties. Dysregulation of the
VEGF-Axxx/
VEGF-Axxxb
isoform balance has recently been reported in several kidney pathologies, including
diabetic nephropathy (DN) and
Denys-Drash syndrome. Using mouse models of
kidney disease where the
VEGF-A isoform balance is disrupted, several reports have shown that VEGF-A165b treatment/over-expression in the kidney is therapeutically beneficial. Furthermore, inhibition of certain splice factor
kinases involved in the regulation of
VEGF-A terminal exon splicing has provided some mechanistic insight into how
VEGF-A splicing could be regulated in the kidney. This review highlights the importance of further investigation into the novel area of
VEGF-A splicing in
chronic kidney disease pathogenesis and how future studies may allow for the development of splicing-modifying therapeutic drugs.