Association of kidney function and uncarboxylated matrix Gla protein: Data from the Heart and Soul Study

Abstract

Background. Vascular calcification is highly prevalent in persons with chronic kidney disease (CKD) and predicts cardiovascular disease (CVD) events. Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification, and lower levels of its precursor - uncarboxylated MGP (ucMGP) - are associated with vascular calcification and atherosclerosis. Whether mild to moderate decrements in kidney function are associated with lower serum ucMGP is unknown.Methods. In a cross-sectional study among 842 outpatients with stable CVD, estimated glomerular filtration rate (eGFR), serum cystatin-C and urine albumin-to-creatinine ratio (ACR) were measured and serum ucMGP levels were determined by ELISA. Multivariate linear regression evaluated the association of each kidney function measure with serum ucMGP levels.Results. The mean eGFR was 76 ± 23 mLmin1.73 m 2, and 186 subjects (22) had moderate CKD (eGFR <60 mLmin1.73 m 2). The mean ± SD ucMGP level was 3289 ± 1177 nM. In unadjusted analysis, each 10 mL min1.73 m 2 lower eGFR was associated with 101 nM lower ucMGP level. This association was only minimally attenuated in final multivariate models wherein each 10 mL min1.73 m 2 lower eGFR was associated with 79 nM lower ucMGP (95 confidence interval CI; 44 to 115; P < 0.001) after adjustment for age, sex, race, body mass index, blood pressure, smoking, hypertension, diabetes; and serum albumin, calcium, phosphorus, and fetuin-A levels. Similarly, in models adjusted for identical covariates, each 0.1mgL higher cystatin-C was associated with 39nM lower ucMGP (95 CI 23 to 55; P < 0.001). In contrast, no significant association was observed between ACR and ucMGP in either unadjusted or adjusted analyses (adjusted P = 0.17). All associations were similar among subjects with or without diabetes (P-values for interaction >0.50). Conclusions. Among outpatients with stable CVD, a reduced glomerular filtration rate is associated with a decreased serum ucMGP level. In contrast, ACR is not associated with ucMGP levels. Whether ucMGP is a useful marker of vascular calcification and CVD event risk in persons with CKD deserves future study.