Circulating Dephospho-Uncarboxylated Matrix Gla-Protein Is Associated With Kidney Dysfunction and Arterial Stiffness
| Autor: | Jonathan Lee, Scott Akers, Khuzaima Javaid, Rachana Miller, Yueya Ge, Garrett Oldland, Zeba Hasmath, Bilal Ansari, Arpita Suri, Houry Puzantian, Raymond R. Townsend, Julio A. Chirinos |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Vitamin medicine.medical_specialty Original Contributions 030232 urology & nephrology Renal function Enzyme-Linked Immunosorbent Assay Pulse Wave Analysis 030204 cardiovascular system & hematology Kidney Peripheral Arterial Disease 03 medical and health sciences chemistry.chemical_compound Vascular Stiffness 0302 clinical medicine Risk Factors Internal medicine Matrix gla protein Vitamin K deficiency Internal Medicine medicine Humans Prospective Studies Renal Insufficiency Chronic Pulse wave velocity Aged Extracellular Matrix Proteins biology business.industry Calcium-Binding Proteins Vitamin K2 Middle Aged Prognosis medicine.disease Up-Regulation Endocrinology chemistry biology.protein Arterial stiffness Female business Biomarkers Glomerular Filtration Rate Kidney disease |
| Zdroj: | American Journal of Hypertension. 31:988-994 |
| ISSN: | 1941-7225 0895-7061 |
| DOI: | 10.1093/ajh/hpy079 |
| Popis: | BACKGROUND Large artery stiffening is increased in advanced chronic kidney disease (CKD) but likely develops progressively in earlier stages of CKD. Active matrix Gla-protein (MGP) is a potent vitamin K–dependent inhibitor of vascular calcification. A recent animal model demonstrated intrinsic abnormalities in vitamin K metabolism even in early CKD, but whether early human CKD is associated with vascular vitamin K deficiency is unknown. METHODS We enrolled 137 adults without HF with varying degrees of renal function: normal estimated glomerular filtration rate (eGFR; >90 ml/min; n = 59), mildly reduced eGFR (stage 2 CKD: eGFR = 60–89 ml/min; n = 53) or at least moderately reduced eGFR (stage 3–5 CKD; eGFR < 60 ml/min; n = 25). Carotid-femoral pulse wave velocity (CF-PWV) was measured with carotid and femoral tonometry. Dephospho-uncarboxylated matrix gla-protein (dp-ucMGP) was measured with enzyme-linked immunosorbent assay (ELISA) (VitaK; Maastricht University; The Netherlands). RESULT Dp-ucMGP levels were progressively increased with decreasing renal function (eGFR ≥ 90: 247 pmol/l; eGFR 60–89: 488 pmol/l; eGFR < 60: 953 pmol/l; P < 0.0001). These differences persisted after adjustment for multiple potential confounders (eGFR ≥ 90: 314 pmol/l; eGFR 60–89: 414 pmol/l; eGFR < 60: 770 pmol/l; P < 0.0001). In a multivariable model adjusted for various confounders, dp-ucMGP was a significant independent predictor of CF-PWV (β = 0.21; P = 0.019). In formal mediation analyses, dp-ucMGP mediated a significant relationship between eGFR and higher CF-PWV (β = −0.16; P = 0.005), whereas no significant dp-ucMGP–independent relationship was present (β = −0.02; P = 0.80). CONCLUSIONS CKD is associated with increased (inactive) dp-ucMGP, a vitamin K–dependent inhibitor of vascular calcification, which correlates with large artery stiffness. Further studies are needed to assess whether vitamin K2 supplementation represents a suitable therapeutic strategy to prevent or reduce arterial stiffening in CKD. |
| Databáze: | OpenAIRE |
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