Endogenous Antiangiogenic Factors in Chronic Kidney Disease: Potential Biomarkers of Progression.

Katsuyuki Tanabe,Yasufumi Sato,Jun Wada

doi:10.3390/ijms19071859

Abstract

Chronic kidney disease (CKD) is a major global health problem. Unless intensive intervention is initiated, some patients can rapidly progress to end-stage kidney disease. However, it is often difficult to predict renal outcomes using conventional laboratory tests in individuals with CKD. Therefore, many researchers have been searching for novel biomarkers to predict the progression of CKD. Angiogenesis is involved in physiological and pathological processes in the kidney and is regulated by the balance between a proangiogenic factor, vascular endothelial growth factor (VEGF)-A, and various endogenous antiangiogenic factors. In recent reports using genetically engineered mice, the roles of these antiangiogenic factors in the pathogenesis of kidney disease have become increasingly clear. In addition, recent clinical studies have demonstrated associations between circulating levels of antiangiogenic factors and renal dysfunction in CKD patients. In this review, we summarize recent advances in the study of representative endogenous antiangiogenic factors, including soluble fms-related tyrosine kinase 1, soluble endoglin, pigment epithelium-derived factor, VEGF-A165b, endostatin, and vasohibin-1, in associations with kidney diseases and discuss their predictive potentials as biomarkers of progression of CKD.

Highlights

Chronic kidney disease (CKD) is one of the most important global health problems
We found potential articles including each antiangiogenic factor as well as terms “kidney”, “renal”, or “glomerular filtration rate (GFR)” based on a PubMed search, and extracted cross-sectional and longitudinal clinical studies that investigated the association between circulating levels of these factors and renal function, except for studies of patients with acute kidney injury and preeclampsia
Urinary vascular endothelial growth factor (VEGF)-A165b and plasma VASH1 levels are likely to be valuable biomarkers, further validations are required in larger studies

Summary

Introduction

Chronic kidney disease (CKD) is one of the most important global health problems. Since peritubular capillary loss and the subsequent renal fibrosis is considered a common pathway in progressive kidney disease, levels of these antiangiogenic factors may have the potential to distinguish patients with relatively rapidly progressive CKD and those with slowly progressive disease. Circulating soluble Flt-1 was demonstrated to be increased in patients with preeclampsia, and to be related to decreased blood levels of VEGF-A, leading to glomerular endothelial injury [8,9]. One clinical study of 130 patients with CKD stage 3a to 5 and 56 controls in Germany reported higher plasma soluble Flt-1 in CKD patients and significant association of the soluble Flt-1 level with decreased estimated glomerular filtration rate (GFR) as well as increased plasma von Willebrand factor, a marker for endothelial dysfunction [21]. Whether circulating soluble Flt-1 could predict the progression of CKD remains unclear, it may be a potential biomarker for cardiovascular events in CKD patients

Soluble Endoglin

VEGF-A165b

Endostatin

Vasohibins

Findings

Conclusions