ASN 2010: Hyponatremia Treatment in the Spotlight at Renal Week

Information on diagnostic and therapeutic approaches to hyponatremia, including tolvaptan and other VRAs, will be presented at this year's conference.

The “Forefronts in Hyponatremia” symposium scheduled to take place today during Renal Week 2010, the 43rd Annual Meeting and Scientific Exposition of the American Society of Nephrology (ASN), will explore diagnostic and therapeutic approaches to hyponatremia, an electrolyte disturbance often associated with kidney malfunction which perturbs cell homeostasis as a result of serum sodium concentrations which fall to lower-than-normal levels.

Physicians in attendance will be consulted in the proper use of vasopressin receptor antagonists (VRAs) such as tolvaptan to fight the complication, and hear case studies further illuminating its effects. Recent clinical reports have stated that therapies making use of VRAs such as tolvaptan, conivaptan, satavaptan and lixivaptan can raise serum concentration at specific points of a treatment regimen, but also increase risk of overly rapid sodium correction.

Hyponatremia has a correlation with illnesses in which sodium is lost due to diarrhea or vomiting, or where excess water accumulates in the body. Some of these ailments include polydipsia and congestive heart failure. Of its three main types of occurrence, hypervolemic hyponatremia is the variety most often is associated with kidney failure. In this manifestation, sodium concentrations become diluted due to an abundance of water in the cells. Sodium losses typically promote hyponatremia in an indirect fashion. Sodium loss leads to a state of volume depletion, which serves as a signal for the release of anti-diuretic hormone. In turn, hormone-stimulated water retention promotes the dilution of sodium. For hospitalized patients, hyponatremia is the most common electrolyte disorder. The VRA conivaptan has often been used to treat hypervolemic hyponatremia, but in recent years the selective vasopressin V2 receptor blocking agent tolvaptan has been introduced to the indication. Both of these antagonists allow for excretion of electrolyte-free water.

Hyponatremia is defined as a serum sodium level of less than 135 mEq/L, and is considered severe when sodium drops below 125 mEq/L. A recent study of five patients at the Lenox Hill Hospital in New York showed that two patients required one 15 mg dose, two patients required two 15 mg doses, and one patient required a single 15 mg dose to achieve SNa levels above 130 meq/L. Urine osmolalities decreased a mean of 243 mOsm/kg H2O. There were no serious drops in blood pressure as a result of the therapy.

Chronic hyponatremia can result in neurological impairments, resulting in perturbed gait, decreased attention, decreased reaction time, falls and osteoporosis. The complication is thus most problematic to geriatric patients. One 2009 study showed that the incidence of hyponatremia in elderly patients with large bone fractures was more than double that of non-fracture patients.

Often, a person who has only mild symptoms associated with hyponatremia can be treated with simple water restriction. It is those patients who suffer congestive heart failure or liver cirrhosis that benefit from vasopressin receptor antagonists. These agents, also known as anti-diuretic hormones, interfere with actions taking place at the vasopressin receptors.

The newer class of receptors have a variety of functions. V1A and V2 receptors are expressed peripherally, and act to modulate blood pressure and kidney functions. Other receptors in this category are expressed in the central nervous system.