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Nonthyroidal illness and the cardiorenal syndrome

Abstract

The cardiorenal syndrome represents a final common pathway for renal and congestive heart failure and heralds a poor prognosis. Factors that link the failing heart and the failing kidneys—the so-called cardiorenal connectors—are, therefore, of clinical and therapeutic interest. Alterations in the levels and function of thyroid hormones that fit the spectrum of nonthyroidal illnesses could be considered to be cardiorenal connectors as both renal failure and heart failure progress with the development of nonthyroidal illness. In addition, circumstantial evidence suggests that nonthyroidal illness can induce deterioration in the function of the heart and the kidneys via multiple pathways. As a consequence, these reciprocal associations could result in a vicious cycle of deterioration that likely contributes to increased mortality. In this Review, we describe the evidence for a pathophysiological role of nonthyroidal illness in the cardiorenal syndrome. We also discuss the available data from studies that have investigated the efficacy of thyroid hormone replacement therapy in patients with renal failure and the rationale for interventional trials to examine the effects of normalization of the thyroid hormone profile in patients with renal failure and congestive heart failure.

Key Points

  • Cardiac disease and renal disease are frequently accompanied by nonthyroidal illness (that is, alterations in thyroid hormones in the absence of hypothalamic–pituitary–thyroidal disease)

  • General factors (such as inflammation and nutritional deficiencies) and pathophysiological factors that are specific to cardiac and renal disease contribute to the development of nonthyroidal illness

  • The presence of nonthyroidal illness is associated with an increased risk of cardiovascular death in patients with cardiac and/or renal disease

  • Nonthyroidal illness can result in deterioration of cardiovascular and renal function via several pathways

  • The genesis of nonthyroidal illness in cardiac and renal failure as well as its deleterious effects on both organ systems suggest that nonthyroidal illness acts as a cardiorenal connector in the cardiorenal syndrome

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Figure 1: Nonthyroidal illness as a cardiorenal connector.
Figure 2: Thyroid hormone levels in nonthyroidal illness.
Figure 3: Direct effects of T3 on the cardiomyocyte.

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Acknowledgements

The authors wish to express their gratitude to J. W. M. Plevier (information specialist at The Walaeus Library, Leiden University Medical Center, Netherlands) for her assistance in the literature search. The authors' work and some of the discussed studies are partially supported by the Westman's foundation, by the Center for Gender Medicine at Karolinska Institutet and by the Swedish Medical Research Council (J. J. Carrero).

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C. L. Meuwese and J. J. Carrero researched the data for the article and wrote the manuscript. All authors made a substantial contribution to discussions of the content and reviewed and/or edited the manuscript before submission.

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Meuwese, C., Dekkers, O., Stenvinkel, P. et al. Nonthyroidal illness and the cardiorenal syndrome. Nat Rev Nephrol 9, 599–609 (2013). https://doi.org/10.1038/nrneph.2013.170

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