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PTH , vitamin D, and the FGF ‐23–klotho axis and heart: Going beyond the confines of nephrology
Author(s) -
NavarroGarcía José Alberto,
FernándezVelasco María,
Delgado Carmen,
Delgado Juan F.,
Kuroo Makoto,
Ruilope Luis M.,
RuizHurtado Gema
Publication year - 2018
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12902
Subject(s) - vitamin d and neurology , medicine , fibroblast growth factor 23 , context (archaeology) , parathyroid hormone , endocrinology , klotho , kidney disease , heart failure , nephrology , left ventricular hypertrophy , kidney , biology , calcium , blood pressure , paleontology
Background Profound disturbances in mineral metabolism are closely linked to the progression of chronic kidney disease. However, increasing clinical and experimental evidence indicates that alterations in phosphate homoeostasis could have an even stronger impact on the heart. Aim The aim of this review is to provide the reader with an update of how alterations in mineral metabolism are related to direct and indirect cardiotoxic effects beyond the nephrology setting. Results Evidence exists that alterations in mineral metabolism that are related to changes in parathyroid hormone ( PTH ), vitamin D, and the FGF ‐23–klotho axis have direct pathological consequences for the heart. Alterations in plasma PTH levels are associated with cardiac dysfunction and detrimental cardiac remodelling. Several clinical studies have associated vitamin D deficiency with the prevalence of cardiovascular disease ( CV ) and its risk factors. Recent evidences support deleterious direct and nonphosphaturic effects of FGF ‐23 on the heart as hypertrophy development. In contrast, reduced systemic klotho levels are related to CV damage, at least when advanced age is present. In addition, we discuss how these mineral metabolism molecules can counteract each other in some situations, in the context of failed clinical trials on cardiac protection as is the case of vitamin D supplementation. Conclusions Among all mineral components, an increase in systemic FGF ‐23 levels is considered to have the greatest CV impact and risk. However, it is quite possible that many intracellular mechanisms mediated by FGF ‐23, especially those related to cardiomyocyte function, remain to be discovered.