Chronic kidney disease (CKD) is closely associated with endothelial dysfunction, leading to symptoms such as albuminuria, edema, and coagulopathy. Recent advancements in single-cell sequencing have deepened our understanding of the heterogeneity of renal endothelial cells, which is significantly influenced by their microenvironment. Understanding the influence of neighboring cells on endothelial heterogeneity is essential for elucidating the mechanisms underlying vascular dysfunction and CKD progression. This review explores the latest research on renal endothelial cell heterogeneity and their interactions with neighboring cells. We further discuss the mechanisms of endothelial injury in CKD, including alterations to the endothelial glycocalyx, inflammation, oxidative stress, and dysfunction of the glomerular filtration barrier. Renal endothelial injury contributes to complications, including cardiovascular disease, diabetic nephropathy, and impaired vascular function. Therapeutic strategies encompass antihypertensive, hypoglycemic, and lipid-lowering treatments, supplemented by emerging approaches such as anti-inflammatory therapies, gene therapy, and lifestyle modifications. Through reviewing the relationship between endothelial injury and CKD progression, we emphasize potential strategies to enhance prognosis and mitigate disease progression.