Journal Article

FGF-23 and osteoprotegerin are independently associated with myocardial damage in chronic kidney disease stages 3 and 4. Another link between chronic kidney disease–mineral bone disorder and the heart

Martin L. Ford, Edward R. Smith, Laurie A. Tomlinson, Prabal K. Chatterjee, Chakravarthi Rajkumar and Stephen G. Holt

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 2, pages 727-733
Published in print February 2012 | ISSN: 0931-0509
Published online July 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr316
FGF-23 and osteoprotegerin are independently associated with myocardial damage in chronic kidney disease stages 3 and 4. Another link between chronic kidney disease–mineral bone disorder and the heart

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Background.

Extra-skeletal calcification and disordered phosphate metabolism are hallmarks of chronic kidney disease–mineral bone disorder (CKD–MBD). Osteoprotegerin (OPG) and fibroblast growth factor 23 (FGF-23) are increased in chronic kidney disease (CKD) and have been associated with arterial and cardiac dysfunction and reduced survival. Troponin T (cTnT) is released from cardiac myocytes under conditions of stress and is predictive of mortality across a range of renal functions. However, the utility of this biomarker was formerly limited by the lower limit of assay detection. The introduction of a high-sensitivity assay has enabled more detailed study of myocyte stress below the previous limit of detection. We studied the association of mediators of CKD–MBD with arterial stiffness and also of these mediators and arterial stiffness with myocardial damage in patients with CKD stages 3–4.

Methods.

OPG and FGF-23 were measured in 200 CKD stages 3–4 patients. cTnT was measured using a high-sensitivity assay. Aortic stiffness was assessed using aortic pulse wave velocity (APWV).

Results.

Mean age was 69 ± 11 years, mean systolic and diastolic blood pressure was 151 ± 22/81 ± 11 mmHg and renal function was 33 ± 11 mL/min/1.73m2. OPG, FGF-23, high-sensitivity troponin T (hs-cTnT) and APWV all correlated with renal function. After multivariate analysis, OPG and age remained independently associated with aortic stiffness. OPG and FGF-23 were independently associated with hs-cTnT in addition to other non-traditional risk factors (Model R2 = 0.596).

Conclusion.

We have shown that changes in bone mediators and phosphate metabolism induced by CKD are independently associated with vascular and cardiomyocyte dysfunction. Our findings suggest that cardiac dysfunction may be specifically associated with such abnormalities in addition to recognized increases in vascular stiffness.

Keywords: arterial stiffness; CKD; FGF-23; osteoprotegerin; troponin

Journal Article.  4526 words. 

Subjects: Nephrology

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