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Increased renal concentrating ability after long-term oral desmopressin lyophilisate treatment contributes to continued success for monosymptomatic nocturnal enuresis

Hirokazu Ikeda, Tsuneki Watanabe and Keiichi Isoyama - Department of Pediatrics, Showa University Fujigaoka Hospital, Yokohama, Kanagawa, Department of Pediatrics, Showa University, Tokyo, Japan

International Journal of Urology, 2017 Jun 21. doi: 10.1111/iju.13394. [Epub ahead of print]

Commentary by Konstantinos Kamperis

Improved renal concentrating capacity in children that remain dry at night following desmopressin treatment. The result of long-term desmopressin treatment?

Desmopressin is first line treatment in nocturnal enuresis with response rates varying depending on the treated population characteristics. The current understanding is that desmopressin is effective while used and discontinuation of the medication is related to high relapse rates. Up to date there is no evidence that desmopressin treatment leads to any sustainable changes in renal function or circadian rhythm of ADH. The authors of this study retrospectively evaluated children that were full responders to desmopressin and attempted to answer the question: Why do some children experience relapse after discontinuation of the medication whereas other remain dry.

The authors hypothesized that children that remained dry after discontinuation of desmopressin differ in terms of renal concentrating capacity compared to the ones experiencing relapse of their bedwetting. Fifty-eight children were included in the study with a mean duration of desmopressin treatment of 18 months. Data on nocturnal urine production as well as the first morning urine osmolality were compared between children who relapse after desmopressin discontinuation and the ones that remained dry. The authors were able to demonstrate that children experiencing relapses shared a higher nocturnal urine output and less concentrated urine during dry nights indicating that these children continue to be in risk of excess urine production and thus enuresis. 

The authors discuss methodological limitations of the study, the main being the fact that urine output on wet nights was not measured and thus one cannot conclude on the exact mechanisms that lead to wet nights after desmopressin discontinuation. 

However, the most important point that needs to be stressed is that the observed changes in the renal concentrating ability in children that become dry on desmopressin are not necessary the result of desmopressin treatment per se. As enuresis has a significant spontaneous cure rate the changes in the renal parameters described in this paper may be the result of alterations in lifestyle, spontaneous changes related to age or other factors.

Whether desmopressin leads to long-term changes in the renal environment is still a hypothesis that needs further investigation.

Abstract

Objectives:

To investigate renal concentrating ability after long-term fast-melting oral desmopressin lyophilisate treatment in children with monosymptomatic nocturnal enuresis.

Methods:

The present retrospective study involved 58 children (43 boys, 15 girls; aged 6-12 years) with nocturnal enuresis receiving oral desmopressin lyophilisate. After treatment for 4 weeks with a complete response, patients were placed on a reduced dose of 120 μg on alternate days. Moring urine osmolality was measured using urine samples obtained after medication and non-medication dry nights. Patients who experienced ≥1 wet nights/month during alternate-day oral desmopressin lyophilisate treatment or within 6 months after its cessation were assigned to the relapse group, whereas those who experienced <1 wet night/month were assigned to the continued success group.

Results:

The continued success and relapse groups included 41 and 17 patients, respectively. The mean duration of treatment was 18.5 and 18.3 months in the continued success group and relapse group, respectively. There was no significant difference in morning urine osmolality after medication nights between the continued success and relapse groups; however, morning urine osmolality after non-medication nights was significantly higher in the continued success group than in the relapse group (P < 0.0001). Similarly, nocturnal urine volume was significantly higher in the relapse group than in the continued success group (P = 0.046).

Conclusions:

These results suggest that patients receiving long-term oral desmopressin lyophilisate treatment develop increased nocturnal renal concentrating ability, which results in sustained dryness even after treatment cessation.

© 2017 The Japanese Urological Association.

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Consensus Guidelines

Practical consensus guidelines for the management of enuresis. 
Evaluation and management of enuresis, a common condition, is not a priority in training programs for medical doctors (MDs), despite being a common condition. 

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Diagnosis and Treatment of Nocturnal Enuresis developed by the Working Group of Nocturnal Enuresis Belgium.