The Role of Vascular Biomarkers in Outcomes of Patients with Kidney Disease

Vascular biomarkers may explain the link between acute kidney injury (AKI) and poor long-term outcomes such as cardiovascular disease (CVD). Vessel injury is exceedingly common in AKI, and contributes to the development of kidney fibrosis and cardiovascular disease (CVD). As prominent determinants of vessel stability in the body, angiopoietins and other prominent vascular biomarkers may explain this biological link. Angiopoietin-1 (Angpt-1) promotes vessel stability by decreasing inflammation, apoptosis and vessel permeability. By contrast, angiopoietin-2 (Angpt-2) blocks the binding of Angpt-1 to its receptor, and thus contributes to vessel instability and permeability. Based on our findings, higher levels of Angpt-1 relative to Angpt -2 were strongly associated with less risk of kidney disease progression, heart failure, and death in hospitalized patients with AKI. In chronic kidney disease patients, it has been shown that endothelial damage in glomerular vasculature triggers Angpt-2 secretion, leading to poor outcomes such as CVD and mortality. Furthermore, in kidney transplant recipients, Angpt-2 levels significantly decrease after transplantation suggesting that transplantation may reduce Angpt-2 levels and decrease rates of poor outcomes. Other vascular health pathways-such as vascular endothelial growth factor (VEGF-A), and placental growth factor (PIGF)-were associated with improved rates of survival after cardiac surgery in participants with and without AKI. Vascular health biomarkers provide actionable pathways for clinical intervention in reducing CVD and mortality for AKI patients. There is great need for future research that focuses on developing robust prognostic vascular biomarker panels in order to help identify high-risk AKI survivors who may benefit from targeted follow-up and therapy, with the intention to prevent kidney and cardiac complications.