Hyponatremia Clinical Update, October 5, 2011

Short-term use of vasopressin receptor antagonists (VRAs) in the treatment of hyponatremia successfully raised serum sodium concentration ([Na(+)](serum)), but additional experience is needed to guide their optimal use and minimize safety concerns, according to the results of a new study.

Researchers from St. Elizabeth’s Medical Center and the Tufts University School of Medicine, both in Boston, conducted a meta-analysis to measure the efficacy and safety of VRAs tested for treatment of hyponatremia in randomized, controlled trials. The study was published in the American Journal of Medicine.

They identified 11 trials with a total of 1,094 patients. Analysis of the data showed that VRAs achieved a net increase in Na(+)](serum) relative to placebo of 3.3 mEq/L at day one (95% confidence interval [CI], 2.7-3.8), and 4.2 mEq/L at day 2 (95% CI, 3.6-4.8). This effect persisted at three to five days, the data showed.

“Larger net increases in [Na(+)](serum) at days one-four were observed in euvolemic hyponatremia and with higher doses. VRAs induced a net increase in effective water clearance relative to placebo of 1244 mL at day one (95% CI, 920-1567), persisting at days two and four,” the authors wrote in the study abstract.

“VRAs were associated with odds ratios of 3.0 for overly rapid correction of [Na(+)](serum) (P <.001), 7.8 for development of hypernatremia (P <.001), 3.3 for thirst development (P <.001), and 2.2 for postural hypotension (P=.04).”

Study Finds Concurrence of Acute Kidney Injury and Hyponatremia

Although acute kidney injury (AKI) is common in patients presenting with hyponatremia and is usually of prerenal origin, the concurrence of AKI and hyponatremia has previously not been emphasized. A new study, however, has done just that and has concluded that the concurrence is important pathophysiologically and that clinicians need to plan rational management for both disorders.

The study, which was published in the Journal of Nephrology, was conducted by researchers in the department of internal medicine at the Erasmus Medical Center in Rotterdam, The Netherlands.

Over the course of four months, the researchers collected clinical, biochemical, treatment, and outcome data for patients presenting with hyponatremia, which the researchers defined as serum sodium=130 mmol/L.

A total of 43 patients were included (serum sodium 126.6 ± 3.7 mmol/L), with the most common causes of hyponatremia being diuretics (n=12), syndrome of inappropriate antidiuretic hormone secretion (n=11), and heart or liver disease (n=5).

In addition, renal insufficiency was frequent (n=18, 42%) and usually represented AKI (n=14, 78%). In patients with AKI, admission serum creatinine was 271 ± 252 µmol/L (3.4 ± 3.1-fold increase from baseline) and the origin was usually prerenal (12/14, 86%, fractional sodium excretion 0.54% ± 0.38%).

“Of these, patients with potentially reversible causes (salt loss or sepsis, n=7) had more favorable outcomes than patients with severe underlying disease (heart or liver disease, n=5), despite similar predictions using the RIFLE criteria. Survivors recovered with fluid resuscitation only. No overly rapid correction of hyponatremia was observed,” the researchers wrote in the study abstract.

In their cohort, the researchers noted, isotonic fluid replacement corrected both disorders and did not lead to overly rapid correction of hyponatremia.

SourcesShort-term Efficacy and Safety of Vasopressin Receptor Antagonists for Treatment of Hyponatremia [American Journal of Medicine]Acute Kidney Injury in Patients Presenting with Hyponatremia [Journal of Nephrology]