Abstract
BackgroundThe pathophysiological mechanisms of renal function progression in chronic kidney disease (CKD) have still not been completely explored. In addition to well-known traditional risk factors, non-traditional risk factors, such as endothelial dysfunction, have gradually attracted physicians' attention. Angiopoietin-2 (Ang-2) impairs endothelial function through preventing angiopoietin-1 from binding to Tie2 receptor. Whether Ang-2 is associated with renal function progression in CKD is unknown.MethodsThis study enrolled 621 patients with stages 3–5 CKD to assess the association of circulating Ang-2 with commencing dialysis, doubling creatinine and rapid decline in renal function (the slope of estimated glomerular filtration rate (eGFR) greater than 5 ml/min per 1.73 m2/y) over follow-up of more than 3 years.ResultsOf all patients, 224 patients (36.1%) progressed to commencing dialysis and 165 (26.6%) reached doubling creatinine. 85 subjects (13.9%) had rapid decline in renal function. Ang-2 quartile was divided at 1494.1, 1948.8, and 2593.1 pg/ml. The adjusted HR of composite outcomes, either commencing dialysis or doubling creatinine was 1.53 (95% CI: 1.06–2.23) for subjects of quartile 4 compared with those of quartile 1. The adjusted OR for rapid decline in renal function was 2.96 (95% CI: 1.13–7.76) for subjects of quartile 4 compared with those of quartile 1. The linear mixed-effects model shows a more rapid decrease in eGFR over time in patients with quartile 3 or more of Ang-2 than those with the lowest quartile of Ang-2.ConclusionsAng-2 is an independent predictor of adverse renal outcome in CKD. Further study is needed to identify the pathogenic role of Ang-2 in CKD progression.
Highlights
Chronic kidney disease (CKD) has been recognized as a worldwide health issue [1]
chronic kidney disease (CKD) was staged according to K/DOQI definitions and the estimated glomerular filtration rate (eGFR) was calculated using the equation of the 4-variable Modification of Diet in Renal Disease (MDRD) Study (CKD stage 3, eGFR: 30–59 ml/min/1.73 m2; CKD stage 4, eGFR: 15–29 ml/min/1.73 m2; CKD stage 5, eGFR,15 ml/ min/1.73 m2) [20]
The proportion of diabetes and b-blocker, serum blood urea nitrogen, phosphate and high-sensitivity C-reactive protein levels, and urine proteincreatinine ratio increased and eGFR, serum hemoglobin, calcium, and albumin levels decreased with Ang-2 quartiles
Summary
The pathophysiological mechanisms of renal function progression in CKD have still not been completely explored. In addition to well-known traditional risk factors, nontraditional risk factors, such as endothelial dysfunction, which might lead to cell apoptosis, vascular regression and renal fibrosis, have gradually attracted physicians’ attention [2]. The rapid release of Ang-2 from endothelial cells upon activation of the endothelium by hypoxia, histamine, and thrombin would disrupt the protective, constitutive Ang-1/Tie signaling by preventing Ang-1 from binding to the receptor [5,7]. The pathophysiological mechanisms of renal function progression in chronic kidney disease (CKD) have still not been completely explored. In addition to well-known traditional risk factors, non-traditional risk factors, such as endothelial dysfunction, have gradually attracted physicians’ attention. Whether Ang-2 is associated with renal function progression in CKD is unknown
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