Effect of Hyponatremia and its Normalization on Patients’ Clinical Outcomes and Bone Metabolism

Abstract

Background: Hyponatremia is an electrolyte disorder affecting up to 40% of hospitalized patients, and has widely been associated with increased risk of death, rehospitalizations, as well as with falls, fractures and osteoporosis, when present on admission. Despite this association, knowledge about beneficial effects of its correction is scare. Additionally, hyponatremia is mostly considered as a surrogate of disease severity rather than a treatable trait, resulting in many patients being and / or remaining hyponatremic at discharge. Objective: This MD-PhD thesis investigates the hypothesis that correction of hyponatremia in hospitalized, adult patients improves their clinical outcome, with particular focus on bone metabolism. Methods: The first study is a secondary analysis of a prospective, placebo-controlled trial to understand the impact of hyponatremia at discharge on clinical outcomes in hospitalized patients with pneumonia. The second study is a registry analysis to investigate the impact of persistency versus normalization of admission hyponatremia on clinical outcomes in hospitalized patients with stroke. The third and main study is the analysis of plasma bone marker changes in relation to serum sodium levels during a prospective, placebo-controlled interventional trial in hospitalized patients with syndrome of inappropriate antidiuresis- (SIAD) induced hyponatremia. Results: Overall, all three studies support the hypothesis that in-hospital correction of hyponatriemia improves the outcome of affected patients. In the setting of pneumonia, hyponatremia at discharge is associated with increased risk of a recurrence within 6 months. In patients with stroke, persistency of initial hyponatremia is associated with a worse functional outcome at 3 months. In patients with SIAD, a targeted correction of hyponatremia stimulates bone formation. Discussion: Newly developed or persistent hyponatremia at discharge is associated with worse clinical outcomes in hospitalized patients. Correction of hyponatremia reverses the hyponatremia-induced negative effect on bone metabolism by stimulating bone formation. Further interventional studies are needed to clarify whether correction of hyponatremia could improve other hyponatremia associated patients’ relevant clinical outcomes analogue to improving bone metabolism as well as long-term of this effect