Abstract
Vascular calcification (VC) is one of the strongest predictors of cardiovascular risk in chronic kidney disease (CKD) patients. New diagnostic/prognostic tools are required for early detection of VC allowing interventional strategies. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor, whose clinical utility is here highlighted. The present study explores, for the first time, correlations between levels of GRP in serum with CKD developmental stage, mineral metabolism markers, VC and pulse pressure (PP), in a cohort of 80 diabetic patients with mild to moderate CKD (stages 2–4). Spearman’s correlation analysis revealed a positive association of GRP serum levels with estimated glomerular filtration rate (eGFR) and α-Klotho, while a negative correlation with phosphate (P), fibroblast growth factor 23 (FGF-23), vascular calcification score (VCS), PP, calcium (x) phosphate (CaxP) and interleukin 6 (IL-6). Serum GRP levels were found to progressively decrease from stage 2 to stage 4 CKD. Multivariate analysis identified low levels of eGFR and GRP, and high levels of FGF-23 associated with both the VCS and PP. These results indicate an association between GRP, renal dysfunction and CKD-mineral and bone disorder. The relationship between low levels of GRP and vascular calcifications suggests a future, potential utility for GRP as an early marker of vascular damage in CKD.
Highlights
Chronic kidney disease (CKD) is estimated to affect more than 10% of the global population and represents an increasing health and economic burden for the society [1,2]
OR, odds ratio; CI, confidence interval; eGFR, estimated glomerular filtration rate; FGF-23, fibroblast growth factor 23; GRP, Gla-rich protein; VCS, vascular calcification score; PP, pulse pressure. This is the first clinical study showing the association of circulating levels of GRP with chronic kidney disease (CKD) pathology and vascular calcification
In adult diabetic patients, serum GRP levels progressively decrease from stage 2 to stage 4 CKD, correlating with markers of mineral metabolism, vascular calcification and pulse pressure
Summary
Chronic kidney disease (CKD) is estimated to affect more than 10% of the global population and represents an increasing health and economic burden for the society [1,2]. Increased vascular stiffness is an established independent predictor of cardiovascular morbidity and mortality [11,12], and aortic calcification has been positively associated with arterial stiffness in the healthy and CKD populations [13,14]. High prevalence of VC in CKD patients is suggested to result from several interconnected processes involving dysregulation of endogenous calcification inhibitors, abnormal mineral metabolism and inflammation [19]. For the first time, the relationship between levels of circulating GRP and chronic renal dysfunction, mineral metabolism and vascular calcifications assessed by the simple vascular calcification score (VCS) and pulse pressure (PP) in a cohort of diabetic patients with mild to moderate CKD (stages 2–4)
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