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Associations between Thyroid Hormones, Calcification Inhibitor Levels and Vascular Calcification in End-Stage Renal Disease.

Meuwese CL, Olauson H, Qureshi AR, Ripsweden J, Barany P, Vermeer C, Drummen N, Stenvinkel P - PLoS ONE (2015)

Bottom Line: Subfractions of MGP, PIVKA-II and sKlotho did not associate with CAC scores and arterial stiffness. fT4 and TSH levels were both inversely associated with CAC scores, but not with arterial stiffness.The positive associations between fT3 and dp-ucMGP and sKlotho suggest that synthesis of MGP and Klotho is influenced by thyroid hormones, and supports a link between non-thyroidal illness and alterations in calcification inhibitor levels.Further studies, measuring total levels of MGP and membrane bound Klotho, should examine this proposed pathway in further detail.

View Article: PubMed Central - PubMed

Affiliation: Department of Renal Medicine, CLINTEC, Karolinska Institutet, Stockholm, Sweden.

ABSTRACT

Introduction: Vascular calcification is a common, serious and elusive complication of end-stage renal disease (ESRD). As a pro-calcifying risk factor, non-thyroidal illness may promote vascular calcification through a systemic lowering of vascular calcification inhibitors such as matrix-gla protein (MGP) and Klotho.

Methods and material: In 97 ESRD patients eligible for living donor kidney transplantation, blood levels of thyroid hormones (fT3, fT4 and TSH), total uncarboxylated MGP (t-ucMGP), desphospho-uncarboxylated MGP (dp-ucMGP), descarboxyprothrombin (PIVKA-II), and soluble Klotho (sKlotho) were measured. The degree of coronary calcification and arterial stiffness were assessed by means of cardiac CT-scans and applanation tonometry, respectively.

Results: fT3 levels were inversely associated with coronary artery calcification (CAC) scores and measures of arterial stiffness, and positively with dp-ucMGP and sKlotho concentrations. Subfractions of MGP, PIVKA-II and sKlotho did not associate with CAC scores and arterial stiffness. fT4 and TSH levels were both inversely associated with CAC scores, but not with arterial stiffness.

Discussion: The positive associations between fT3 and dp-ucMGP and sKlotho suggest that synthesis of MGP and Klotho is influenced by thyroid hormones, and supports a link between non-thyroidal illness and alterations in calcification inhibitor levels. However, the absence of an association between serum calcification inhibitor levels and coronary calcification/arterial stiffness and the fact that MGP and Klotho undergo post-translational modifications underscore the complexity of this association. Further studies, measuring total levels of MGP and membrane bound Klotho, should examine this proposed pathway in further detail.

No MeSH data available.


Related in: MedlinePlus

Coronary artery calcification scores across tertiles of fT3.
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pone.0132353.g002: Coronary artery calcification scores across tertiles of fT3.

Mentions: Cardiac CT-scans (n = 65) showed that 26.2, 15.4 and 13.9 percent of patients had CAC scores over 100, 400 and 800 AU, respectively. A dose response association was observed between fT3 tertiles and CAC scores; a significantly larger part of patients in the lower fT3 tertiles vs. those in the highest tertile had CAC scores >400 AU (Fig 2). Logistic regression analyses confirmed this association and showed that, per pmol/L increase in fT3, the adjusted odds [95% CI] for having CAC scores >400 AU was 0.19 [0.05–0.74, p = 0.017] lower. Linear regression analyses showed an average (95% CI) decrease in CAC scores (β: -179 [: -356 to -1] p = 0.048) with an increment of one pmol/L in fT3 concentration, persisting after adjustment (β: -164 [-329 to 1] p = 0.051). TSH levels showed an inverse association with CAC scores; (per logTSH increase, adjusted odds for having CAC levels >100 AU and >400 AU decreased with 0.3 [0.1–0.8, p = 0.019] and 0.4 [0.1–1.0, p = 0.049], respectively (S1 Appendix)). Higher fT4 levels associated with an increased adjusted odds for having CAC scores > 100 AU by 13 [1.0–1.6, p = 0.021]. Neither TSH nor fT4 levels were associated with parameters of vascular stiffness (S1 Appendix).


Associations between Thyroid Hormones, Calcification Inhibitor Levels and Vascular Calcification in End-Stage Renal Disease.

Meuwese CL, Olauson H, Qureshi AR, Ripsweden J, Barany P, Vermeer C, Drummen N, Stenvinkel P - PLoS ONE (2015)

Coronary artery calcification scores across tertiles of fT3.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492991&req=5

pone.0132353.g002: Coronary artery calcification scores across tertiles of fT3.
Mentions: Cardiac CT-scans (n = 65) showed that 26.2, 15.4 and 13.9 percent of patients had CAC scores over 100, 400 and 800 AU, respectively. A dose response association was observed between fT3 tertiles and CAC scores; a significantly larger part of patients in the lower fT3 tertiles vs. those in the highest tertile had CAC scores >400 AU (Fig 2). Logistic regression analyses confirmed this association and showed that, per pmol/L increase in fT3, the adjusted odds [95% CI] for having CAC scores >400 AU was 0.19 [0.05–0.74, p = 0.017] lower. Linear regression analyses showed an average (95% CI) decrease in CAC scores (β: -179 [: -356 to -1] p = 0.048) with an increment of one pmol/L in fT3 concentration, persisting after adjustment (β: -164 [-329 to 1] p = 0.051). TSH levels showed an inverse association with CAC scores; (per logTSH increase, adjusted odds for having CAC levels >100 AU and >400 AU decreased with 0.3 [0.1–0.8, p = 0.019] and 0.4 [0.1–1.0, p = 0.049], respectively (S1 Appendix)). Higher fT4 levels associated with an increased adjusted odds for having CAC scores > 100 AU by 13 [1.0–1.6, p = 0.021]. Neither TSH nor fT4 levels were associated with parameters of vascular stiffness (S1 Appendix).

Bottom Line: Subfractions of MGP, PIVKA-II and sKlotho did not associate with CAC scores and arterial stiffness. fT4 and TSH levels were both inversely associated with CAC scores, but not with arterial stiffness.The positive associations between fT3 and dp-ucMGP and sKlotho suggest that synthesis of MGP and Klotho is influenced by thyroid hormones, and supports a link between non-thyroidal illness and alterations in calcification inhibitor levels.Further studies, measuring total levels of MGP and membrane bound Klotho, should examine this proposed pathway in further detail.

View Article: PubMed Central - PubMed

Affiliation: Department of Renal Medicine, CLINTEC, Karolinska Institutet, Stockholm, Sweden.

ABSTRACT

Introduction: Vascular calcification is a common, serious and elusive complication of end-stage renal disease (ESRD). As a pro-calcifying risk factor, non-thyroidal illness may promote vascular calcification through a systemic lowering of vascular calcification inhibitors such as matrix-gla protein (MGP) and Klotho.

Methods and material: In 97 ESRD patients eligible for living donor kidney transplantation, blood levels of thyroid hormones (fT3, fT4 and TSH), total uncarboxylated MGP (t-ucMGP), desphospho-uncarboxylated MGP (dp-ucMGP), descarboxyprothrombin (PIVKA-II), and soluble Klotho (sKlotho) were measured. The degree of coronary calcification and arterial stiffness were assessed by means of cardiac CT-scans and applanation tonometry, respectively.

Results: fT3 levels were inversely associated with coronary artery calcification (CAC) scores and measures of arterial stiffness, and positively with dp-ucMGP and sKlotho concentrations. Subfractions of MGP, PIVKA-II and sKlotho did not associate with CAC scores and arterial stiffness. fT4 and TSH levels were both inversely associated with CAC scores, but not with arterial stiffness.

Discussion: The positive associations between fT3 and dp-ucMGP and sKlotho suggest that synthesis of MGP and Klotho is influenced by thyroid hormones, and supports a link between non-thyroidal illness and alterations in calcification inhibitor levels. However, the absence of an association between serum calcification inhibitor levels and coronary calcification/arterial stiffness and the fact that MGP and Klotho undergo post-translational modifications underscore the complexity of this association. Further studies, measuring total levels of MGP and membrane bound Klotho, should examine this proposed pathway in further detail.

No MeSH data available.


Related in: MedlinePlus