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Longer duration of obesity is associated with a reduction in urinary angiotensinogen in prepubertal children

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Abstract

Background

We aimed to study the impact of obesity on urinary excretion of angiotensinogen (U-AGT) in prepubertal children, focusing on the duration of obesity and gender. Also, we aimed to evaluate whether plasma angiotensinogen (P-AGT) and hydrogen peroxide (H2O2) play a role in the putative association.

Methods

Cross-sectional evaluation of 305 children aged 8–9 years (160 normal weight, 86 overweight, and 59 obese). Anthropometric measurements and 24-h ambulatory blood pressure monitoring were performed. Angiotensinogen (AGT) was determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit and H2O2 by a microplate fluorometric assay.

Results

U-AGT and P-AGT levels were similar across body mass index (BMI) groups and between sexes. However, boys who were overweight/obese since the age of 4 years presented lower levels of U-AGT compared with those of normal weight at the same age. In children who were overweight/obese since the age of 4, urinary H2O2 decreased with P-AGT.

Conclusions

A higher duration of obesity was associated with decreased U-AGT in boys, thus reflecting decreased intrarenal activity of the renin–angiotensin system. Also, children with a longer duration of obesity showed an inverse association between urinary H2O2 and P-AGT. Future studies should address whether these results reflect an early compensatory mechanism to limit obesity-triggered renal dysfunction.

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Acknowledgements

The authors gratefully acknowledge the families enrolled in Generation XXI for their kindness, all members of the research team for their enthusiasm and perseverance and the participating hospitals and their staff for their help and support.

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Author notes

  1. Manuela Morato and Liane Correia-Costa contributed equally as first authors to this paper.

  2. Ana Azevedo and António Albino-Teixeira contributed equally to the supervision and scientific revision of this paper.

Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, Faculty of Medicine of University of Porto, Porto, Portugal

    Manuela Morato, Teresa Sousa, Dina Cosme & António Albino-Teixeira

  2. Department of Drug Sciences, Laboratory of Pharmacology, Faculty of Pharmacy of the University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal

    Manuela Morato

  3. MedInUP - Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal

    Manuela Morato, Teresa Sousa & António Albino-Teixeira

  4. Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy of University of Porto, Porto, Portugal

    Manuela Morato

  5. EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal

    Liane Correia-Costa, Dina Cosme, Alberto Caldas Afonso, Henrique Barros & Ana Azevedo

  6. Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal

    Liane Correia-Costa & Alberto Caldas Afonso

  7. Department of Pediatrics, Faculty of Medicine of University of Porto, Porto, Portugal

    Liane Correia-Costa, António Guerra & Alberto Caldas Afonso

  8. Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany

    Franz Schaefer

  9. Division of Pediatric Cardiology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal

    José Carlos Areias

  10. Division of Pediatric Nutrition, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal

    António Guerra

  11. CINTESIS - Center for Research in Health Technologies and Information Systems, Faculty of Medicine, University of Porto, Porto, Portugal

    António Guerra

  12. Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine of University of Porto, Porto, Portugal

    Henrique Barros & Ana Azevedo

Authors
  1. Manuela Morato
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  2. Liane Correia-Costa
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  3. Teresa Sousa
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  4. Dina Cosme
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  5. Franz Schaefer
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  6. José Carlos Areias
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  7. António Guerra
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  8. Alberto Caldas Afonso
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  9. Henrique Barros
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  10. Ana Azevedo
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  11. António Albino-Teixeira
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Corresponding author

Correspondence to Manuela Morato.

Ethics declarations

The Generation XXI study was approved by the Ethics Committee of Centro Hospitalar São João, E.P.E. and Faculty of Medicine of the University of Porto, Portugal, and by the National Data Protection Commission. It complies with the Helsinki Declaration and the current national legislation. Written informed consent from parents (or their legal substitute) and verbal assent from children was obtained, concerning information and biological samples gathering.

Conflicts of interest

None of the authors have any financial or nonfinancial competing interests concerning the present study.

Sources of funding

This project was supported by funds from Fundo Europeu de Desenvolvimento Regional (FEDER) from Programa Operacional Factores de Competitividade – COMPETE (FCOMP-01-0124-FEDER-028751), by national funds from the Portuguese Foundation for Science and Technology (FCT) (PTDC/DTP-PIC/0239/2012) and by Calouste Gulbenkian Foundation, that granted the study design and data collection and analysis. Liane Correia-Costa was supported by FCT (grant SFRH/SINTD/95898/2013), Teresa Sousa was supported by FCT and POPH/FSE (EC) (Ciência 2008 and SFRH/BPD/112005) and Franz Schaefer was supported by the ERA-EDTA Research Programme and the KfH Foundation for Preventive Medicine. The Epidemiology Research Unit (EPIUnit) is funded by FCT (UID/DTP/04750/2013).

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Morato, M., Correia-Costa, L., Sousa, T. et al. Longer duration of obesity is associated with a reduction in urinary angiotensinogen in prepubertal children. Pediatr Nephrol 32, 1411–1422 (2017). https://doi.org/10.1007/s00467-017-3639-y

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