The association of angiogenic factors and chronic kidney disease

Christopher E Anderson,Swapna G Kallu,Myra A Kleinpeter,N Kevin Krane,Jiang He,L Lee Hamm,Eric E Simon,Ravi Siriki,Damodar R Kumbala,Chung-Shiuan Chen,Gem Batuman,Jing Chen,Shilpa Gadde

doi:10.1186/s12882-018-0909-2

Christopher E Anderson, Swapna G Kallu + Show 11 more

Open Access

https://doi.org/10.1186/s12882-018-0909-2

Copy DOI

Abstract

BackgroundThere are limited data on the associations of circulating angiogenic factors with chronic kidney disease (CKD). We investigate the associations of circulating vascular endothelial growth factor (VEGF)-A, angiopoietin-1, angiopoietin-1/VEGF-A ratio, VEGF receptor 1 (VEGFR-1), VEGFR-2, and pentraxin-3 with CKD.MethodsWe recruited 201 patients with CKD and 201 community controls without CKD from the greater New Orleans area. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or presence of albuminuria. Multivariable quantile and logistic regression models were used to examine the relationship between angiogenesis-related factors and CKD adjusting for confounding factors.ResultsAfter adjusting for covariables including traditional cardiovascular disease (CVD) risk factors, C-reactive protein, and history of CVD, the medians (interquartile range) were 133.08 (90.39, 204.15) in patients with CKD vs. 114.17 (72.45, 170.32) pg/mL in controls without CKD (p = 0.002 for group difference) for VEGF-A; 3951.2 (2471.9, 6656.6) vs. 4270.5 (2763.7, 6537.2) pg/mL (p = 0.70) for angiopoietin-1; 25.87 (18.09, 47.90) vs. 36.55 (25.71, 61.10) (p = 0.0001) for angiopoietin-1/VEGF-A ratio; 147.81 (122.94, 168.79) vs. 144.16 (123.74, 168.05) ng/mL (p = 0.25) for VEGFR-1; 26.20 (22.67, 29.92) vs. 26.28 (23.10, 29.69) ng/mL (p = 0.31) for VEGFR-2; and 1.01 (0.79, 1.49)vs. 0.89 (0.58, 1.18) ng/mL (p = 0.01) for pentraxin-3, respectively. In addition, an elevated VEGF-A level and decreased angiopoietin-1/VEGF-A ratio were associated with increased odds of CKD.ConclusionsThese data indicate that plasma VEGF-A and pentraxin-3 levels were increased and the angiopoietin-1/VEGF-A ratio was decreased in patients with CKD. Future prospective studies are warranted to examine whether angiogenic factors play a role in progression of CKD.

Highlights

There are limited data on the associations of circulating angiogenic factors with chronic kidney disease (CKD)
These data indicate that plasma vascular endothelial growth factor (VEGF)-A and pentraxin-3 levels were increased and the angiopoietin-1/ VEGF-A ratio was decreased in patients with CKD
The present study indicated that higher VEGF-A and pentraxin-3 levels and a lower angiopoietin-1/VEGF-A ratio may be associated with increased risk of CKD

Summary

Introduction

There are limited data on the associations of circulating angiogenic factors with chronic kidney disease (CKD). Chronic Kidney Disease (CKD) is a highly prevalent disease, affecting over 26.3 million adults in the US alone and 497.5 million in the world [1, 2]. CKD has been associated with increased risks of end-stage renal disease (ESRD), cardiovascular disease (CVD), and premature death [3, 4]. Traditional risk factors only partially explain excess risk of CKD and associated ESRD and CVD in the general. Animal studies have suggested the involvement of an imbalance of angiogenic factors in the pathogenesis of kidney disease [8,9,10,11,12,13,14]. Deletion of angiopoietin-1 coupled with microvascular stress resulted in organ damage, accelerated angiogenesis and fibrosis [18].

Objectives

Methods

Results

Discussion

Conclusion