Abstract
BackgroundAn intact angiopoietin/Tie-2 ligand receptor system is indispensable for life. High circulating angiopoietin-2 (Ang-2) concentrations are strongly associated with kidney disease involving the progressive loss of glomerular filtration. The aim of our study was to investigate the associations between renal function and serum Ang-2 or serum Tie-2 concentrations in the general population.MethodsData of 3081 and 4088 subjects from two population-based studies, the Study of Health in Pomerania (SHIP-1) and SHIP-Trend, were used. Renal function was assessed by serum creatinine, cystatin C concentration, creatinine-based estimated glomerular filtration rate [eGFR(crea)], cystatin C-based eGFR [eGFR(cys)] and urinary albumin-to-creatinine ratio (uACR). Analyses of variance and linear regression models were calculated.ResultsIn both cohorts, strong positive associations between serum cystatin C concentrations and serum Ang-2 or Tie-2 concentrations as well as inverse associations between eGFR(cys) and serum Ang-2 or Tie-2 concentrations were found. These relations were also present in a subpopulation without hypertension or diabetes mellitus type 2. Furthermore, we detected weak U-shaped associations between serum creatinine concentrations or eGFR(crea) and serum Ang-2 concentrations. With respect to uACR a strong positive association with serum Ang-2 concentrations was revealed.ConclusionSerum Ang-2 concentrations are strongly associated with sensitive parameters of renal impairment like serum cystatin C, uACR and eGFR(cys). These findings persisted even after exclusion of subjects with hypertension or diabetes mellitus type 2, conditions that predispose to chronic renal disease and are associated with increased Ang-2 concentrations. Interestingly, we did not detect the same strong relations between serum creatinine and eGFR(crea) with serum Ang-2 concentration. Additionally, significant association of serum Tie-2 concentrations with cystatin C and eGFR(cys) were detected.
Highlights
The angiopoietin/Tie-2 ligand receptor system is an important regulator of the vascular integrity and endothelial cell homeostasis [1]
Renal function was assessed by serum creatinine, cystatin C concentration, creatinine-based estimated glomerular filtration rate [estimated GFR (eGFR)(crea)], cystatin C-based eGFR [eGFR(cys)] and urinary albumin-to-creatinine ratio
Serum Ang-2 concentrations are strongly associated with sensitive parameters of renal impairment like serum cystatin C, urinary albumin-to-creatinine ratio (uACR) and eGFR(cys)
Summary
The angiopoietin/Tie-2 ligand receptor system is an important regulator of the vascular integrity and endothelial cell homeostasis [1]. The best known ligands of the system are angiopoietin 1 (Ang-1) and angiopoietin 2 (Ang-2), two endothelial growth factors [1] that bind to the same extracellular domain of the Tie-2 receptor, but evoke opposing biological effects [2]. Ang-2 is synthesized by endothelial cells and stored in Weibel-Palade bodies[1, 4]. Hypoxia, altered shear stress or soluble factors like VEGF and TNFα are stimuli for the rapid release of Ang-2 from Weibel-Palade bodies [1, 4]. High circulating angiopoietin-2 (Ang-2) concentrations are strongly associated with kidney disease involving the progressive loss of glomerular filtration. The aim of our study was to investigate the associations between renal function and serum Ang-2 or serum Tie-2 concentrations in the general population.
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