Abstract
Background: Zinc-alpha 2-glycoprotein (AZGP1), a secreted protein with ubiquitous tissue expression, has been controversially linked to the risk of cardiovascular disease. In a cohort of kidney transplant recipients, we measured serum AZGP1 levels after transplantation over a 2 year period and tested for an association with pulse wave velocity as an important parameter indicating future cardiovascular events.Methods: Annual blood sampling and pulse wave velocity measurements were longitudinally performed in 113 kidney transplant recipients. AZGP1 was measured in serum samples using standard ELISA. Association of AZGP1 with pulse wave velocity was longitudinally assessed during follow up of 2 years by mixed longitudinal modeling.Results: AZGP1 serum levels declined significantly after kidney transplantation. This decline was dependent on allograft function as indicated by inverse correlation with eGFR. When corrected for eGFR multivariable analysis revealed an inverse correlation between AZGP1 and pulse wave velocity. This analysis further showed independent associations of older age, higher blood pressure, and higher calcium phosphate product with higher pulse wave velocity.Conclusions: Improved kidney function after transplantation leads to a decline in AZGP1 serum levels. Independent of kidney function and other cardiovascular risk factors lower AZGP1 levels are associated with higher pulse wave velocity in the 2 years after kidney transplantation. These data suggest that AZGP1 might be a potential biomarker for cardiovascular health and a target for improving cardiovascular outcome.
Highlights
Cardiovascular disease (CVD) is the leading cause of death in patients with end stage renal disease (ESRD) [1]
As AZGP1 is partially cleared by the kidney, increased serum levels can be observed in patients with kidney dysfunction [11,12,13]
While higher AZGP1 levels were associated with reduced incidence of coronary heart disease and atherosclerosis in non-chronic kidney disease (CKD) patients [14, 15], higher AZGP1 levels were shown to correlate positively with CVD in ESRD patients [16]
Summary
Cardiovascular disease (CVD) is the leading cause of death in patients with end stage renal disease (ESRD) [1]. Zinc-alpha 2-glycoprotein, AZGP1 (often abbreviated as ZAG) is a secreted 43 kDa protein which is expressed by many tissues leading to a serum concentration of 30–70 μg/ml in healthy individuals. While higher AZGP1 levels were associated with reduced incidence of coronary heart disease and atherosclerosis in non-CKD patients [14, 15], higher AZGP1 levels were shown to correlate positively with CVD in ESRD patients [16]. It is interesting, that so far, AZGP1 has not been investigated in the context of kidney transplantation. In a cohort of kidney transplant recipients, we measured serum AZGP1 levels after transplantation over a 2 year period and tested for an association with pulse wave velocity as an important parameter indicating future cardiovascular events
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