Dataset Information

Differences in the urinary metabolome and proteome between wet and dry nights in children with monosymptomatic nocturnal enuresis and nocturnal polyuria.

ABSTRACT:

Background

Nocturnal enuresis (NE) is a common disease with multiple pathogenic mechanisms. This study aimed to compare levels of metabolites and proteins between wet and dry nights in urine samples from children with monosymptomatic NE (MNE).

Methods

Ten boys with MNE and nocturnal polyuria (age: 7.6 ± 1.3 years) collected their total nighttime urine production during a wet and a dry night. Untargeted metabolomics and proteomics were performed on the urine samples by liquid chromatography coupled with high-mass accuracy tandem mass spectrometry (LC-MS/MS).

Results

On wet nights, we found reduced urine osmolality (P = 0.025) and increased excretion of urinary potassium and sodium by a factor of, respectively, 2.1 (P = 0.038) and 1.9 (P = 0.19) compared with dry nights. LC-MS identified 59 metabolites and 84 proteins with significantly different levels between wet and dry nights (fold change (FC) < 0.67 or > 1.5, P < 0.05). Some compounds were validated by different methodologies. During wet nights, levels of compounds related to oxidative stress and blood pressure, including adrenalin, were increased. We found reduced levels of aquaporin-2 on wet nights. The FCs in the 59 metabolites were positively correlated to the FCs in the same metabolites identified in urine samples obtained during the evening preceding wet and dry nights.

Conclusions

Oxidative stress, which in the literature has been associated with nocturia and disturbances in sleep, might be increased during wet nights in children with MNE. We further found evidence of increased sympathetic activity. The mechanisms related to having wet nights in children with MNE seem complex, and both free water and solute handling appear to be important. A higher resolution version of the Graphical abstract is available as Supplementary information.

SUBMITTER: Jorgensen CS

PROVIDER: S-EPMC10465629 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Differences in the urinary metabolome and proteome between wet and dry nights in children with monosymptomatic nocturnal enuresis and nocturnal polyuria.

Jørgensen Cecilie Siggaard CS Kamperis Konstantinos K Knudsen Jane Hagelskjær JH Kjeldsen Margrethe M Christensen Jane Hvarregaard JH Borch Luise L Rittig Søren S Palmfeldt Johan J

Pediatric nephrology (Berlin, Germany) 20230504 10

<h4>Background</h4>Nocturnal enuresis (NE) is a common disease with multiple pathogenic mechanisms. This study aimed to compare levels of metabolites and proteins between wet and dry nights in urine samples from children with monosymptomatic NE (MNE).<h4>Methods</h4>Ten boys with MNE and nocturnal polyuria (age: 7.6 ± 1.3 years) collected their total nighttime urine production during a wet and a dry night. Untargeted metabolomics and proteomics were performed on the urine samples by liquid chrom ...[more]

PMID: 37140712

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Project description:Objectives: Nocturnal enuresis (NE) is a common pediatric condition, and desmopressin (dDAVP) is a first-line therapy for NE. The standard initial dosage of dDAVP is 0. 2 mg/day, and most guidelines recommend that the dose should be increased at 0.2 mg increments until dryness is achieved or to the maximal recommended dose. However, previous evidence has shown that this strategy seems insufficient to further improve efficacy and results in unnecessarily high doses for some patients. Our study aimed to assess the efficacy of our modified dDAVP treatment regimen in children with MNE in China and evaluate predictive factors associated with the dDAVP response. Methods: All MNE patients at the Department of Nephrology at Children's Hospital of Fudan University from January to December 2019 were prospectively and consecutively enrolled. dDAVP treatment comprised a dose titration period and a 3-month maintenance period. The efficacy of dDAVP was assessed according to the latest International Children's Continence Society criteria at the end of the study. Predictive factors were evaluated by logistic regression analysis. Results: Overall, 322 MNE patients were enrolled in our study, and 225 (69.9%) completed the study. The intention to treat analysis showed that the overall dDAVP response rate was 69.9%: among these patients 32.3% were complete responders, and 37.6% were partial responders. At the end of the study, 194/225 (86.2%) patients received a final dose of 0.2 mg, 24/225 (10.7%) patients received a final dose of 0.3 mg, and 7/225 (3.1%) patients received a final dose of 0.4 mg. Multivariate analysis showed that patients requiring lower doses to achieve responses were significantly more likely to experience complete response during the maintenance period [odds ratio (OR)=9.683; 95% confidence interval (CI), 2.770-33.846]. Conclusions: Our results indicate that the dDAVP treatment regimen provides a comparable efficacy to the international conventional treatment regimen with a lower overall dose. Low-dose responders were likely to achieve a complete response without increasing the dose; in these cases, the maximum dose might not be necessary.

Project description:PurposeThe pathophysiology of nocturia and nocturnal polyuria (NP), conditions that become more prevalent with aging, may in part be explained by changes in hormones involved in water homeostasis. The purpose of this study was to analyze the impact of aging on urinary natriuretic peptides in nocturia and NP.MethodsPatients aged ≥18 years completed 24-hour bladder diaries for assessment of nocturia and NP. They were divided into subgroups of ≥65 years old and <65 years old. Urine samples were collected and analyzed for natriuretic peptide (NT-proANP, NT-proBNP, and NT-proCNP) levels. Peptide levels were compared between patients with and without nocturia/NP and within age subgroups; correlation to the NP index (NPi) was determined.ResultsCompared to patients without nocturia (N=15), patients with nocturia (N=36) had higher median levels of urinary NT-proANP (15.8 pmol/mmol Cr vs. 10.9 pmol/mmol Cr, P=0.016) and NT-proBNP (6.3 pmol/mmol Cr vs. 4.5 pmol/mmol Cr, P=0.021), but showed no differences in NT-proCNP (2.4 pmol/mmol Cr vs. 2.5 pmol/mmol Cr, P=0.967). Patients ≥65 years old with nocturia had higher NT-proANP (29.8 pmol/mmol Cr vs. 11.0 pmol/mmol Cr, P<0.001) and NT-proBNP (9.6 pmol/mmol Cr vs. 5.0 pmol/mmol Cr, P<0.001) than patients <65 years old. Additionally, patients with NP (N=30) showed higher urinary NT-proANP (19.6 pmol/mmol Cr vs. 10.5 pmol/mmol Cr, P<0.001) and NT-proBNP (6.7 pmol/mmol Cr vs. 4.7 pmol/mmol Cr, P=0.020) compared to patients without NP (N=21). NP patients ≥65 years had higher NT-proANP (29.8 pmol/mmol Cr vs. 12.5 pmol/mmol Cr, P<0.001) and NT-proBNP (9.6 pmol/mmol Cr vs. 4.4 pmol/mmol Cr, P=0.004) than patients <65 years old. NPi positively correlated with urinary NT-proANP (RS=0.417, P=0.002) and NT-proBNP (RS=0.303, P=0.031), but not with NT-proCNP (RS=-0.094, P=0.510).ConclusionSince urinary NT-proANP and NT-proBNP were greater in aged patients with nocturia and NP, natriuretic peptides may contribute to the pathophysiology of these conditions and further research should aim to explore them as targets for management.

Dataset Information

Differences in the urinary metabolome and proteome between wet and dry nights in children with monosymptomatic nocturnal enuresis and nocturnal polyuria.

Background

Methods

Results

Conclusions

Publications

Differences in the urinary metabolome and proteome between wet and dry nights in children with monosymptomatic nocturnal enuresis and nocturnal polyuria.

Similar Datasets

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