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Salivary metabolic profile of children and adolescents after hemodialysis

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Abstract

Introduction

The application of metabolomic analysis in the pediatric nephrology field may offer an innovative approach to profile analysis of renal diseases.

Objective

We aimed to analyze the salivary the major metabolites in the saliva of children and adolescents with chronic kidney disease (CKD) before and after hemodialysis.

Method

Thirty-six children diagnosed with CKD and forty healthy children were recruited for the study. 1H-NMR spectra were analyzed using multivariate and univariate approaches.

Results

The CKD and the healthy control groups presented with similar numbers of dental caries (p > 0.05) as determined by the number of decayed, missing, or filled deciduous teeth (0.87 ± 2.2 and 0.67 ± 2.1, respectively) or permanent teeth (0.79 ± 1.30 and 0.90 ± 1.7, respectively). The amount of dental calculus was significantly higher in the CKD group than in the healthy control group (p < 0.001). Multivariate analyses using PLS-DA and O-PLS-DA demonstrated differences in the salivary metabolome of CKD patients before and after hemodialysis, as well as between post-dialysis CKD patients and healthy controls, suggesting that HD was not able to recover oral homeostasis. PLS-DA and OPLS-DA models showed satisfactory accuracy (ACC = 0.72) and prediction (0.64). On multivariate and univariate analyses, urea, acetate, ethanol, and fatty acid were significantly decreased in CKD saliva after hemodialysis. By contrast, saliva from the healthy controls had significantly higher levels of acetate and propionate and lower levels of ethanol, lactate, butyrate, phenylalanine, and creatinine than saliva from post-dialysis CKD patients.

Conclusion

Our results demonstrate that hemodialysis alters the expression of salivary metabolites; however, this alteration does not reestablish the healthy salivary metabolome, as the salivary metabolomic profile of healthy children is significantly different from that of children and adolescents with CKD, both before and after hemodialysis. The unique salivary characteristics of children with CKD may influence their oral health status.

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Abbreviations

CKD:

Chronic kidney disease

CRR:

Creatinine reduction rate

CPMG:

Carr-Purcell-Meiboom-Gill

dmft:

Decayed, missing, or filled deciduous teeth

DMFT:

Decayed, missing, or filled permenant teeth

HD:

Hemodialysis

HD-A:

After hemodialysis

HD-B:

Before hemodialysis

NMR:

Nuclear magnetic resonance

O-PLS-DA:

Orthogonal partial least squares discriminant analysis

PLS-DA:

Partial least squares discriminant analysis

TOCSY:

Total correlation spectroscopy

URR:

Urea reduction rate

VIP:

Variable importance in projection

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Acknowledgements

The authors acknowledge the hemodialysis centers and the doctors Alberto Zagury and Gisella Pires Mello for their medical support.

Funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq (306214/2013; 303785/2014-4; 426265/2016-5), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ (201.278/2014; 620.012/2015; 202.902/2015), Centro Nacional de Ressonância Magnética Nuclear (CNRMN), and Instituto Nacional de Ciência and Tecnologia de Biologia Estrutural e Bioimagem (InBEB).

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All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.

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Correspondence to Ivete P. R. Souza or Ana Paula Valente.

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Ethical approval

This study analyzes collected data which involved human participants. This study was approved by the Local Ethical Committee (Comitê de Ética em Pesquisa do Hospital Federal de Bonsucesso - CEP-HFB 28/10).

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Written informed consent was obtained from all participants or their respective legal representative.

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Almeida, P.A., Fidalgo, T.K.S., Freitas-Fernandes, L.B. et al. Salivary metabolic profile of children and adolescents after hemodialysis. Metabolomics 13, 141 (2017). https://doi.org/10.1007/s11306-017-1283-y

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