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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

Associations between fT3 and t-ucMGP (A), dp-ucMGP (B), PIVKA (C), and sKlotho (D).
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pone.0132353.g003: Associations between fT3 and t-ucMGP (A), dp-ucMGP (B), PIVKA (C), and sKlotho (D).

Mentions: With an increase in fT3 tertile, and although not statistically significant, a gradual increase in plasma levels of dp-uc-MGP and sKlotho was noted (Table 2). Plasma levels of t-ucMGP, and PIVKA did not differ between the different fT3 tertiles. Fig 3 illustrates scatterplots of the associations between fT3 and t-ucMGP (A), dp-ucMGP (B), PIVKA-II (C) and sKlotho (D). As shown in Table 3, results from linear regression analyses confirmed a statistically significant association between fT3 and dp-uc-MGP (β: 0.15 [0.05 to 0.25] p = 0.004) and between fT3 and sKlotho (β: 0.12 [0.01 to 0.22] p = 0.031). Only the association between fT3 and Log(dp-ucMGP) persisted after adjustment for age, sex, diabetes mellitus, cardiovascular disease, vintage, IL-6 levels, SGA, PIVKA-II and albumin levels. FT3 levels were not significantly associated with t-uc-MGP and PIVKA-II. fT4 and TSH concentrations were not associated with calcification inhibitor levels (S1 Appendix). As expected, PIVKA-II associated with dp-ucMGP (Rho = 0.32, p = 0.01).


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)

Associations between fT3 and t-ucMGP (A), dp-ucMGP (B), PIVKA (C), and sKlotho (D).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132353.g003: Associations between fT3 and t-ucMGP (A), dp-ucMGP (B), PIVKA (C), and sKlotho (D).
Mentions: With an increase in fT3 tertile, and although not statistically significant, a gradual increase in plasma levels of dp-uc-MGP and sKlotho was noted (Table 2). Plasma levels of t-ucMGP, and PIVKA did not differ between the different fT3 tertiles. Fig 3 illustrates scatterplots of the associations between fT3 and t-ucMGP (A), dp-ucMGP (B), PIVKA-II (C) and sKlotho (D). As shown in Table 3, results from linear regression analyses confirmed a statistically significant association between fT3 and dp-uc-MGP (β: 0.15 [0.05 to 0.25] p = 0.004) and between fT3 and sKlotho (β: 0.12 [0.01 to 0.22] p = 0.031). Only the association between fT3 and Log(dp-ucMGP) persisted after adjustment for age, sex, diabetes mellitus, cardiovascular disease, vintage, IL-6 levels, SGA, PIVKA-II and albumin levels. FT3 levels were not significantly associated with t-uc-MGP and PIVKA-II. fT4 and TSH concentrations were not associated with calcification inhibitor levels (S1 Appendix). As expected, PIVKA-II associated with dp-ucMGP (Rho = 0.32, p = 0.01).

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