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Low-dose desmopressin combined with serum sodium monitoring can prevent clinically significant hyponatraemia in patients treated for nocturia

Juul KV, Malmberg A, van der Meulen E, Walle JV, Nørgaard JP

BJU Int. 2016 Nov 15. doi: 10.1111/bju.13718

Commentary by Philip Van Kerrebroeck

Desmopressin is an internationally recognized therapy for nocturia as a consequence of nocturnal polyuria. In clinical practice, especially in elderly individuals, desmopressin indications are limited by the gear of hyponatremia. Recently  two low-dose formulations of desmopressin have been registered in Europe for the treatment of nocturia in males and females. In this article, the risk factors for desmopressin-induced hyponatraemia are studied and the impact of a serum sodium monitoring plan is evaluated.

The article presents data of a meta-analysis from three clinical trials of desmopressin in nocturia. In these clinical trials patients with nocturia were randomized between placebo or different dosages of a desmopressin orally disintegrating tablet (ODT; 10-100 μg). In the studied cohort the incidence of serum sodium <130 mmol/L was recorded by age, sex and dose. Furthermore potential predictors of clinically significant hyponatraemia were identified using multivariate analysis in a Cox proportional hazards model.

The authors discriminate the following significant risk factors for hyponatremia in both sexes: dose of desmopressin, age of patient, baseline serum sodium level and kidney function, according to estimated GFR clearance. These findings confirm  similar known risk factors associated with hyponatraemia in the general population. In men, arthritis and use of drugs for bone disease were also found to be predictive of hyponatraemia. In women however, raised monocytes and absence of lipid-modifying drugs increased the risk of hyponatraemia. Based on these results it is concluded that the use of the proposed monitoring scheme and the minimum effective dose would have omitted all patients with clinically significant hyponatraemia from further treatment.

As a practical conclusion with clinical consequences, the authors indicate that the incidence of hyponatraemia can be reduced by using minimum effective gender-specific dosing with the ODT formulation of desmopressin. This dosage is defined at 25 μg in women, and 50 μg in men. They also propose to install a sodium monitoring plan whereby baseline sodium must be ≥135 mmol/L (especially in the age group >65). Additional monitoring is advised at week 1 and month 1 for those at elevated risk (aged ≥65, receiving concomitant medication associated with hyponatraemia). This monitoring plan would help to prevent some at-risk patients developing hyponatraemia.

This study confirms the clinical potential of low dose desmopressin for a safe and effective treatment of nocturia, also in elderly individuals as well females as males.