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Evaluation of Urinary Aquaporin 2 and Plasma Copeptin as Biomarkers of Effectiveness of Desmopressin Acetate for the Treatment of Monosymptomatic Nocturnal Enuresis.
J Urol. 2017 10; 198(4):921-927.JU

Abstract

PURPOSE

Desmopressin is a synthetic V2 specific analogue of antidiuretic hormone (arginine vasopressin) that is widely used as first line treatment for monosymptomatic nocturnal enuresis. However, no biomarkers to predict desmopressin effectiveness have yet been established. Because arginine vasopressin is unstable, we prospectively measured the major urine concentration factor aquaporin 2 and serum copeptin (as a surrogate marker for vasopressin) in patients with monosymptomatic nocturnal enuresis, and evaluated whether they are useful for predicting desmopressin treatment outcome.

MATERIALS AND METHODS

The study included 32 children 6 to 11 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria. Exclusion criteria were daytime urinary symptoms and underlying diseases causing nocturnal enuresis. Subjects were treated with 120 μg or 240 μg desmopressin oral disintegrating tablet and were divided into responders (at 120 or 240 μg) and nonresponders (at 240 μg). Day/night ratios of plasma copeptin and urinary aquaporin 2 were measured during desmopressin treatment.

RESULTS

There was no significant difference in baseline day/night ratio of urinary aquaporin 2 between desmopressin responders and nonresponders. After 8 weeks of treatment there was a significant correlation between day/night ratio of aquaporin 2 and percentage of wet nights. In responders (but not nonresponders) there was a significant difference in the change in aquaporin 2 day/night ratio from before treatment to complete remission (p = 0.0004). For plasma copeptin the baseline day/night ratio for responders at 120 μg was significantly lower than in the 240 μg nonresponder group (p = 0.02).

CONCLUSIONS

Urinary aquaporin 2 appears to be a biomarker of desmopressin treatment effectiveness during therapy, while plasma copeptin levels before treatment are predictive of desmopressin response.

Authors+Show Affiliations

Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.Department of Pediatrics, Juntendo University Nerima Hospital, Tokyo, Japan. Electronic address: ohtomo@juntendo-nerima.jp.Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.Department of Pediatrics, Juntendo University Nerima Hospital, Tokyo, Japan.Department of Pharmacology, Keio University School of Medicine, Tokyo, Japan.Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

28457803

Citation

Hara, Taichi, et al. "Evaluation of Urinary Aquaporin 2 and Plasma Copeptin as Biomarkers of Effectiveness of Desmopressin Acetate for the Treatment of Monosymptomatic Nocturnal Enuresis." The Journal of Urology, vol. 198, no. 4, 2017, pp. 921-927.
Hara T, Ohtomo Y, Endo A, et al. Evaluation of Urinary Aquaporin 2 and Plasma Copeptin as Biomarkers of Effectiveness of Desmopressin Acetate for the Treatment of Monosymptomatic Nocturnal Enuresis. J Urol. 2017;198(4):921-927.
Hara, T., Ohtomo, Y., Endo, A., Niijima, S., Yasui, M., & Shimizu, T. (2017). Evaluation of Urinary Aquaporin 2 and Plasma Copeptin as Biomarkers of Effectiveness of Desmopressin Acetate for the Treatment of Monosymptomatic Nocturnal Enuresis. The Journal of Urology, 198(4), 921-927. https://doi.org/10.1016/j.juro.2017.04.088
Hara T, et al. Evaluation of Urinary Aquaporin 2 and Plasma Copeptin as Biomarkers of Effectiveness of Desmopressin Acetate for the Treatment of Monosymptomatic Nocturnal Enuresis. J Urol. 2017;198(4):921-927. PubMed PMID: 28457803.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of Urinary Aquaporin 2 and Plasma Copeptin as Biomarkers of Effectiveness of Desmopressin Acetate for the Treatment of Monosymptomatic Nocturnal Enuresis. AU - Hara,Taichi, AU - Ohtomo,Yoshiyuki, AU - Endo,Amane, AU - Niijima,Shinichi, AU - Yasui,Masato, AU - Shimizu,Toshiaki, Y1 - 2017/04/28/ PY - 2017/04/24/accepted PY - 2017/5/2/pubmed PY - 2019/4/16/medline PY - 2017/5/2/entrez KW - aquaporin 2 KW - deamino arginine vasopressin KW - nocturnal enuresis KW - pediatrics SP - 921 EP - 927 JF - The Journal of urology JO - J. Urol. VL - 198 IS - 4 N2 - PURPOSE: Desmopressin is a synthetic V2 specific analogue of antidiuretic hormone (arginine vasopressin) that is widely used as first line treatment for monosymptomatic nocturnal enuresis. However, no biomarkers to predict desmopressin effectiveness have yet been established. Because arginine vasopressin is unstable, we prospectively measured the major urine concentration factor aquaporin 2 and serum copeptin (as a surrogate marker for vasopressin) in patients with monosymptomatic nocturnal enuresis, and evaluated whether they are useful for predicting desmopressin treatment outcome. MATERIALS AND METHODS: The study included 32 children 6 to 11 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria. Exclusion criteria were daytime urinary symptoms and underlying diseases causing nocturnal enuresis. Subjects were treated with 120 μg or 240 μg desmopressin oral disintegrating tablet and were divided into responders (at 120 or 240 μg) and nonresponders (at 240 μg). Day/night ratios of plasma copeptin and urinary aquaporin 2 were measured during desmopressin treatment. RESULTS: There was no significant difference in baseline day/night ratio of urinary aquaporin 2 between desmopressin responders and nonresponders. After 8 weeks of treatment there was a significant correlation between day/night ratio of aquaporin 2 and percentage of wet nights. In responders (but not nonresponders) there was a significant difference in the change in aquaporin 2 day/night ratio from before treatment to complete remission (p = 0.0004). For plasma copeptin the baseline day/night ratio for responders at 120 μg was significantly lower than in the 240 μg nonresponder group (p = 0.02). CONCLUSIONS: Urinary aquaporin 2 appears to be a biomarker of desmopressin treatment effectiveness during therapy, while plasma copeptin levels before treatment are predictive of desmopressin response. SN - 1527-3792 UR - https://www.unboundmedicine.com/medline/citation/28457803/Evaluation_of_Urinary_Aquaporin_2_and_Plasma_Copeptin_as_Biomarkers_of_Effectiveness_of_Desmopressin_Acetate_for_the_Treatment_of_Monosymptomatic_Nocturnal_Enuresis_ L2 - https://www.jurology.com/doi/full/10.1016/j.juro.2017.04.088?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -