Role of vascular endothelial growth factor in kidney disease.
Vascular endothelial growth factor (VEGF) is a main regulator of blood vessel growth and plays an important role in promoting endothelial survival and maintaining the microvasculature. The kidney is a highly vascularized organ and has two important microvasculatures; glomerular and peritubular capillaries. Loss of these capillaries is strongly associated with the progression of chronic kidney disease (CKD) to end-stage renal disease. In several kidney disease animal models, VEGF expression in the kidney is decreased and administration of VEGF is protective. Recent clinical observations revealed that blocking VEGF by endogenous inhibitor (soluble Flt-1) in preeclampsia and monoclonal antibody against VEGF in cancer patients cause proteinuria and renal dysfunction. However, plasma VEGF levels in diabetic nephropathy patients are increased and blocking VEGF improved diabetic nephropathy in animal models. Increased plasma VEGF levels have been reported in CKD patients. Deleterious effects of VEGF have been demonstrated in atherosclerosis and sepsis, which are frequent complications in CKD patients. Although administrating VEGF or novel drugs that activate VEGF pathway may improve the progression of CKD, careful monitoring will be required when CKD patients have complications of diabetes, atherosclerosis or sepsis.
Doi
Kent
K
Department of Nephrology and Endocrinology, University of Tokyo, Tokyo, Japan. kdoi-tky@umin.ac.jp
Noiri
Eisei
E
Fujita
Toshiro
T
D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000150:complications; D003928:Diabetic Nephropathies / Q000188:drug therapy; D018450:Disease Progression; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D055806:Microvessels / Q000187:drug effects / Q000503:physiopathology; D018805:Sepsis / Q000097:blood / Q000150:complications; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000502:physiology / Q000627:therapeutic use; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology* / Q000627:therapeutic use
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1