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Open AccessArticle

Angiopoietin-2: A Potential Mediator of the Glycocalyx Injury in Adult Nephrotic Patients

Medical Sciences Postgraduate Program, Universidade de Fortaleza–UNIFOR, Fortaleza 60811-905, Ceara, Brazil
Medical Course, Universidade de Fortaleza—UNIFOR, Fortaleza 60811-905, Ceara, Brazil
Department of Clinical Medicine, Universidade Christus, Fortaleza 60811-905, Ceara, Brazil
Medical Sciences Postgraduate Program, Department of Clinical Medicine, Universidade Federal do Ceará, Fortaleza 60811-905, Ceará, Brazil
Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Ceara, Fortaleza 60811-905, Ceara, Brazil
Experimental Biology Centre (NUBEX), University of Fortaleza (UNIFOR), Fortaleza 60811-905, Ceara, Brazil
Author to whom correspondence should be addressed.
J. Clin. Med. 2018, 7(11), 401;
Received: 24 September 2018 / Revised: 20 October 2018 / Accepted: 22 October 2018 / Published: 31 October 2018
PDF [499 KB, uploaded 31 October 2018]


Introduction: Glomerulopathy is a group of diseases that affect mainly young adults between the ages of 20 and 40 years. Recently, it has been demonstrated that syndecan-1, a biomarker of endothelial glycocalyx damage, is increased in nephrotic patients with near-normal renal function and it is important to endothelial dysfunction in these patients. Angiopoietin-2 (AGPT2) is an endothelial growth factor that promotes cell derangement. Here we evaluated AGPT2 levels in patients with nephrotic syndrome, near-normal renal function and the possible interaction of AGPT2 with endothelial glycocalyx derangement. Methods: This was a cross-sectional study performed from January through November 2017. Adult patients (age > 18 years) with nephrotic syndrome and without immunosuppression were included. Blood samples were drawn after a 12 h fast for later measurement of syndecan-1 and AGPT2. Mediation analyses were performed to assess the hypothesized associations of nephrotic syndrome features and AGPT2 with syndecan-1. Results: We included 65 patients, 37 (56.9%) of them female, with primary glomerular disease. Syndecan-1 in nephrotic patients was higher than in control individuals (102.8 ± 36.2 vs. 28.2 ± 9.8 ng/mL, p < 0.001). Correlation of syndecan-1 with the main features of nephrotic syndrome after adjustment for age and estmmated glomerular filtration rate (eGFR) demonstrated that syndecan-1 was significantly associated with 24-h urinary protein excretion, total cholesterol, LDL (low density lipoprotein)-cholesterol, HDL (high-density lipoprotein)-cholesterol, and triglycerides. Angiopoietin-2 was independently associated with serum albumin, 24 h urinary protein excretion, total cholesterol, and LDL-cholesterol, in addition to being strongly associated with syndecan-1 (0.461, p < 0.001). The results of the mediation analyses showed that the direct association between LDL-cholesterol and syndecan-1 was no longer significant after AGPT-2 was included in the mediation analysis. AGPT2 explained 56% of the total observed association between LDL-cholesterol and syndecan-1. Conclusion: The association between LDL-cholesterol and glycocalyx derangement in nephrotic patients is possibly mediated by AGPT2. View Full-Text
Keywords: Agiopoietin-2; mediation analysis; nephrotic syndrome Agiopoietin-2; mediation analysis; nephrotic syndrome

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Chaves, M.M.S.; Mendes, M.S.; Schwermann, M.P.; Queiroz, R.; Coelho, R.F.; Salmito, F.T.S.; Meneses, G.C.; Martins, A.M.C.; Moreira, A.C.O.M.; Libório, A.B. Angiopoietin-2: A Potential Mediator of the Glycocalyx Injury in Adult Nephrotic Patients. J. Clin. Med. 2018, 7, 401.

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