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Association of angiopoietin-2 with renal outcome in chronic kidney disease.

ABSTRACT: 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. 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.This 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.Of 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.Ang-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.

SUBMITTER: Tsai YC

PROVIDER: S-EPMC4184837 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Association of angiopoietin-2 with renal outcome in chronic kidney disease.

Tsai Yi-Chun YC Chiu Yi-Wen YW Tsai Jer-Chia JC Kuo Hung-Tien HT Lee Su-Chu SC Hung Chi-Chih CC Lin Ming-Yen MY Hwang Shang-Jyh SJ Kuo Mei-Chuan MC Chen Hung-Chun HC

PloS one 20141003 10

<h4>Background</h4>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. 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 C ...[more]

PMID: 25279852

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Project description:Background: T-lymphocyte subsets reflect patients' immune status and are associated with adverse outcomes in various diseases. However, the association between T-lymphocyte subsets and major infection and renal outcome in chronic kidney disease (CKD) patients has not been well-addressed. Methods: Patients diagnosed with stage 3-5 of non-dialysis CKD were recruited, and healthy subjects were selected as the controls. T-lymphocyte subsets (CD3+, CD4+, CD8+) were detected by flow cytometry, and the CD4+/CD8+ T cell ratio was then calculated. Patients were divided into the normal-level group and the low-level group according to the clinical reference value. The primary outcomes were the major infection and renal outcome. Results: A total of 410 CKD patients were enrolled; the average age was 47.25 years. Compared to the healthy controls, the level of CD3+, CD4+, CD8+ T cells, and the CD4+/CD8+ T cell ratio were significantly decreased in CKD patients (p < 0.05). During the median follow-up of 2.56 (quartile interval 1.24-3.46) years, major infections occurred in 15.10% of the CKD patients. The incidence of infection was significantly higher in the low-level group of CD3+, CD4+ T cells, and CD4+/CD8+ T cell ratio compared with the normal level groups. Kaplan-Meier analysis showed that the lower level of CD3+, CD4+ T cells, and CD4+/CD8+T cell ratio is associated with a greater risk of infection. Cox regression analysis further confirmed that low CD3+, CD4+ T cells, and CD4+/CD8+ T cell ratio were independent risk factors of infection in CKD patients. Moreover, during the follow-up, renal events occurred in 37.50% of patients. Kaplan-Meier analysis indicated that low levels of CD3+, CD4+, and CD8+ T cells are significantly associated with renal outcome in CKD patients. Cox regression analysis showed that low level of CD3+ T cells (HR = 2.407, 95% CI: 1.664-3.482, p < 0.001), CD4+ T cells (HR = 2.397, 95% CI: 1.633-3.518, p < 0.001) and CD8+ T cells (HR = 2.416, 95% CI: 1.476-3.955, p < 0.001) were independent risk factors for renal outcome after multivariable-adjusted. Conclusion: CKD patients had a defect in T-lymphocyte subpopulation. T-lymphocyte subsets were closely associated with infection and renal outcome in CKD patients. Suggesting T-lymphocyte subsets are independent predictors of infection and renal outcome in CKD patients.

Dataset Information

Association of angiopoietin-2 with renal outcome in chronic kidney disease.

Publications

Association of angiopoietin-2 with renal outcome in chronic kidney disease.

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