Circulating Soluble Fms-like Tyrosine Kinase in Renal Diseases Other than Preeclampsia

• Published in: Journal of the American Society of Nephrology Vol. 32; no. 8; pp. 1853 - 1863
• Main Authors: Wewers, Theresa M, Schulz, Annika, Nolte, Ingo, Pavenstädt, Hermann, Brand, Marcus, Di Marco, Giovana S
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01-08-2021
• Subjects: Acute Kidney Injury - blood; Acute Kidney Injury - surgery; Biomarkers - blood; Coronary Vessels - pathology; Endothelium - physiopathology; Female; Humans; Kidney - blood supply; Kidney - pathology; Kidney Transplantation; Microvessels - pathology; Pre-Eclampsia - blood; Pregnancy; Renal Dialysis; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - therapy; Reviews; Vascular Endothelial Growth Factor Receptor-1 - blood; cardiovascular disease; chronic kidney disease; risk factors; acute renal failure; renal transplantation; vascular endothelial growth factor; kidney disease; soluble Fms-like tyrosine kinase
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2020111579

Soluble Fms-like tyrosine kinase (sFlt-1/sVEGFR1) is a naturally occurring antagonist of vascular endothelial growth factor (VEGF). Despite being a secreted, soluble protein lacking cytoplasmic and transmembrane domains, sFlt-1 can act locally and be protective against excessive microenvironmental VEGF concentration or exert autocrine functions independently of VEGF. Circulating sFlt-1 may indiscriminately affect endothelial function and the microvasculature of distant target organs. The clinical significance of excess sFlt-1 in kidney disease was first shown in preeclampsia, a major renal complication of pregnancy. However, circulating sFlt-1 levels appear to be increased in various diseases with varying degrees of renal impairment. Relevant clinical associations between circulating sFlt-1 and severe outcomes (
endothelial dysfunction, renal impairment, cardiovascular disease, and all-cause mortality) have been observed in patients with CKD and after kidney transplantation. However, sFlt-1 appears to be protective against renal dysfunction-associated aggravation of atherosclerosis and diabetic nephropathy. Therefore, in this study, we provide an update on sFlt-1 in several kidney diseases other than preeclampsia, discuss clinical findings and experimental studies, and briefly consider its use in clinical practice.