Nonthyroidal illness and the cardiorenal syndrome.

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.