Combination treatment of nocturnal enuresis with desmopressin and indomethacin

Pediatr Nephrol. 2017 Apr;32(4):627-633. doi: 10.1007/s00467-016-3536-9. Epub 2016 Oct 27.

Abstract

Background: We investigated the effect of combining indomethacin and desmopressin in treating children with monosymptomatic nocturnal enuresis (MNE) and desmopressin-resistant nocturnal polyuria.

Methods: Twenty-three children with MNE, nocturnal polyuria, and partial or no response to desmopressin were recruited from incontinence clinics of our tertiary referral center. We used a randomized single-arm crossover placebo-controlled study design consisting of two 3-week treatment periods with a combination of desmopressin (0.4 mg) and indomethacin (50 mg) or desmopressin and placebo at bedtime. Home recordings at baseline and for the final 2 weeks of each treatment period were performed and included nocturnal urine output measurements. The number of dry nights achieved and reduction in the nocturnal urine output were the main effect parameters. Student's t test and Pearson's correlation coefficient were used for statistical analysis.

Results: The addition of indomethacin to desmopressin significantly reduced nocturnal urine output (from 324 ± 14 ml to 258 ± 13 ml, p < 0.001). This did not lead to more dry nights in all children, and we found no statistically significant reduction in enuresis frequency (from 68 % ± 0.1 to 56 % ± 0.1, p = 0.24).

Conclusions: Addition of indomethacin to desmopressin can further reduce nocturnal urine output in children with MNE and desmopressin-resistant nocturnal polyuria. The combination treatment does not, however, improve outcome in terms of frequency of nights with enuresis. The dissociation of antidiuretic and antienuretic effect may reflect nocturnal bladder reservoir dysfunction in children who present with normal daytime bladder function.

Trial registration: ClinicalTrials.gov NCT00226122.

Keywords: Children; Natriuresis; Nocturnal polyuria; Osmotic diuresis; Prostaglandins.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Child
  • Cross-Over Studies
  • Deamino Arginine Vasopressin / adverse effects
  • Deamino Arginine Vasopressin / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Indomethacin / adverse effects
  • Indomethacin / therapeutic use*
  • Male
  • Nocturnal Enuresis / drug therapy*
  • Polyuria / drug therapy
  • Renal Agents / adverse effects
  • Renal Agents / therapeutic use*
  • Urodynamics / drug effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Renal Agents
  • Deamino Arginine Vasopressin
  • Indomethacin

Associated data

  • ClinicalTrials.gov/NCT00226122