Tolvaptan in the Treatment of Acute Hyponatremia Associated with Acute Kidney Injury

Hyponatremia defined as a plasma sodium concentration of less than 135？mmol/L is a very common disorder, occurring in hospitalized patients. Hyponatremia often results from an increase in circulating arginine vasopressin (AVP) levels and/or increased renal sensitivity to AVP, combined with an increased intake of free water. Hyponatremia is subdivided into three groups, depending on clinical history and volume status: hypovolemic, euvolemic, and hypervolemic. Acute symptomatic hyponatremia is usually treated with hypertonic (3%) saline. Syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH) and hypervolemic hyponatremia caused by heart failure or cirrhosis are treated with vasopressin antagonists (vaptans) since they increase plasma sodium (Na2+) concentration via their aquaretic effects (augmentation of free-water clearance). The role of tolvaptan in the treatment of acute hyponatremia and conversion of oliguric to nonoliguric phase of acute tubular necrosis has not been previously described. 1. Introduction Acute kidney injury is a frequent complication in critically ill patients and is difficult to manage as it is often accompanied by oliguria or anuria as well as total body fluid overload and edema. Optimal management of volume status as well as normalizing serum sodium levels is essential. Sodium concentration is the major determinant of plasma osmolality; therefore, hyponatremia usually indicates a low plasma osmolality. Low plasma osmolality rather than hyponatremia, per se, is the primary cause of the symptoms of hyponatremia. Hyponatremia not accompanied by hypoosmolality does not cause signs or symptoms and does not require specific treatment [1]. The limitation in the kidney’s ability to excrete water in hyponatremic states is, in most cases, due to the persistent action of antidiuretic hormone (ADH, vasopressin). ADH acts at the distal nephron to decrease the renal excretion of water. The action of ADH is, therefore, to concentrate the urine and, as a result, dilute the serum. Under normal circumstances, ADH release is stimulated primarily by hyperosmolality. However, under conditions of severe intravascular volume depletion or hypotension, ADH may be released even in the presence of serum hypoosmolality [1]. Hyponatremia and impaired urinary dilution can be caused by either a primary or a secondary defect in the regulation of AVP secretion or action. The primary forms are generally referred to as the syndrome of inappropriate antidiuresis (SIADH). When osmotic suppression of antidiuresis is impaired for any reason, retention