An exploratory pilot study with copeptin as a biomarker for individualizing treatment for nocturnal polyuria.

OBJECTIVE: The aim of the present study was to investigate the use of random copeptin concentrations as possible biomarkers for the differential diagnosis of nocturnal polyuria (NP). METHODS: In all, 111 patients with and without nocturia were enrolled in the study. Patients with a neurogenic bladder and/or those who had undergone bladder or urethral surgery were excluded from the study. All patients completed a 72-hour frequency-volume chart and a renal function profile. A random blood sample was obtained during the day for measurement of plasma copeptin concentrations, osmolality, and serum sodium and creatinine concentrations. The effect of the use of different definitions for NP was evaluated. RESULTS: The median age of the study participants was 61 years, and 48% were female. Copeptin was significantly correlated with urinary and plasma osmolality, as well as free water clearance (r=0.43, 0.56 and -0.38 respectively; P < .001 for all). Study participants were divided into 3 groups: controls (n = 51), those with NP (n = 41), and those with global polyuria (n = 19). Copeptin concentrations were significantly lower in subjects with global polyuria than in those with NP and the control group (2.96 vs 3.97 and 3.94 pM, respectively; P = .008 and .005). There was no significant difference in random daytime copeptin concentrations between the NP and control groups (P = .972). The results differed when other definitions for NP were used (e.g. NPi33 or NUP10). CONCLUSIONS: We could not confirm our hypothesis that patients with NP have lower copeptin concentrations, although random blood sampling is not ideal. Further research is required to determine the use of copeptin in NP, perhaps in the identification of the desmopressin response.

Questions to ask a patient with nocturia.

BACKGROUND: Patients may not raise nocturia as a concern as they mistakenly consider the symptom to be a normal part of ageing. Nocturia is associated with significant morbidity and is likely to be a marker of poor health. OBJECTIVE: This paper provides questions to guide diagnosis, evaluation and individualised treatment of nocturia. DISCUSSION: Nocturia results from the interplay between nocturnal polyuria, reduced bladder storage and sleep disruption. Changes in the function of the urinary bladder, kidneys, brain and cardiovascular system, and hormone status underlie the development and progression of nocturia. Medications commonly prescribed to older people can affect development or resolution of nocturia. The bother caused to a patient by waking to void relates to disturbance of slow-wave sleep, the physical act of getting out of bed and resulting chronic fatigue. An assessment process that identifies relevant and co-existing causes of an individual's nocturia will facilitate a targeted approach to treatment.

Desmopressin 30 years in clinical use: a safety review.

Desmopressin acetate is the synthetic analogue of the antidiuretic hormone arginine vasopressin. It has been employed clinically for >30 years in a range of formulations: intranasal solution (since 1972), injectable solution (since 1981), tablets (since 1987), and most recently, an oral lyophilisate (since 2005). The antidiuretic properties of desmopressin have led to its use in polyuric conditions including primary nocturnal enuresis, nocturia, and diabetes insipidus. While a large body of clinical data is available for desmopressin, and despite its widespread use, comprehensive reviews of the safety of desmopressin are lacking (although some case series have attempted to correlate patient and/or dosing characteristics with the occurrence of adverse reactions). The purpose of this paper is to review the safety of desmopressin, based on analyses of both published data (MedLine) and of adverse reactions reported to Ferring Pharmaceuticals, the major manufacturer of desmopressin. Based on the findings, suggested strategies to reduce the risk of adverse reactions are proposed. Treatment with intranasal and oral formulations of desmopressin is generally well tolerated, and side effects are usually minor. The risk of hyponatraemia, although small, can be reduced by adhering to the indications, dosing recommendations and precautions when prescribing desmopressin.

The pharmacokinetics of 400 microg of oral desmopressin in elderly patients with nocturia, and the correlation between the absorption of desmopressin and clinical effect.

OBJECTIVE: To investigate the pharmacokinetic profile of oral desmopressin in elderly patients with nocturia, and to analyse any possible correlation between the absorption and clinical effect. PATIENTS AND METHODS: In all, 32 patients were screened to determine the baseline number of nocturnal voids and the nocturia index; of these, 24 fulfilled the inclusion criteria and were enrolled for a pharmacokinetic evaluation of oral desmopressin 400 microg. A double-blind, randomized, placebo-controlled, crossover-effect evaluation period was then used to test the association between the absorption of desmopressin and pharmacodynamic effect. Serial plasma samples were collected for 8 h for a pharmacokinetic analysis of desmopressin. The pharmacodynamics after an equivalent oral dose before bedtime were assessed by measuring changes in the number of nocturnal voids, time to first nocturnal void and nocturnal diuresis, from placebo to active treatment. RESULTS: There was a linear relationship between plasma desmopressin at 2 h after dosing and the area under the plasma concentration curve from 0 to infinity (Pearson's rho 0.923, P < 0.001). Women had a significantly higher plasma desmopressin concentration than men (P = 0.0012) and more adverse events. There was no correlation between plasma desmopressin at 2 h after dosing and the within-patient response in any of the effect variables. Generally, the number of nocturnal voids and nocturnal diuresis were half that with placebo. The time to the first nocturnal void was almost doubled compared with placebo. CONCLUSIONS: There seems to be a relationship between gender, plasma level of desmopressin and the incidence of adverse events. Plasma desmopressin at 2 h after dosing cannot be used to predict the pharmacodynamic response, although desmopressin lowers the nocturnal diuresis and the number of nocturnal voids.