Impact of Angiopoietin-2 on Kidney Diseases

Abstract

<b><i>Background:</i></b> Angiopoietins (Ang) are essential angiogenic factors involved in angiogenesis, vascular maturation, and inflammation. The most studied angiopoietins, angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), behave antagonistically to each other in vivo to sustain vascular endothelium homeostasis. While Ang-1 typically acts as the endothelium-protective mediator, its context-dependent antagonist Ang-2 can promote endothelium permeability and vascular destabilization, hence contributing to a poor outcome in vascular diseases via endothelial injury, vascular dysfunction, and microinflammation. The pathogenesis of kidney diseases is associated with endothelial dysfunction and chronic inflammation in renal diseases. <b><i>Summary:</i></b> Several preclinical studies report overexpression of Ang-2 in renal tissues of certain kidney disease models; additionally, clinical studies show increased levels of circulating Ang-2 in the course of chronic kidney disease, implying that Ang-2 may serve as a useful biomarker in these patients. However, the exact mechanisms of Ang-2 action in renal diseases remain unclear. <b><i>Key Messages:</i></b> We summarized the recent findings on Ang-2 in kidney diseases, including preclinical studies and clinical studies, aiming to provide a systematic understanding of the role of Ang-2 in these diseases.

Associations of Angiopoietin 2 and Vascular Endothelial Growth Factor-A Concentrations with Clinical End Points

“…The methods and main results of the CREDENCE trial have been described previously. 16,17 In brief, the CREDENCE study compared the efficacy of canagliflozin 100 mg versus placebo in lowering cardiorenal events among 4401 people with type 2 diabetes mellitus and kidney disease. Participants in the study were to have a minimum glycated hemoglobin level between 6.5% and 12.0%, an eGFR of 30–90 ml/min per 1.73 m 2 , and a urine albumin–creatinine ratio of >300–5000 mg/g.…”

“…7 Accordingly, there is interest in evaluating these biomarkers in DKD. 16 In this study, using data from study participants with available samples for analysis in the Canagliflozin and Kidney Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, we sought to assess the association between angiopoietin 2 and cardiorenal outcomes and further investigate the effect of canagliflozin on angiopoietin 2 concentrations. The direct effect of SGLT2is on angiopoietin 2 levels has not been reported previously.…”