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Unacylated ghrelin and obestatin: promising biomarkers of protein energy wasting in children with chronic kidney disease

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Abstract

Background

Impairment in orexigenic/anorexigenic hormone balance may be key in the pathogenesis of protein energy wasting in children with chronic kidney disease (CKD). Measurement of ghrelin and obestatin concentrations in children with CKD would help assess the potential contribution of these hormones to uremic protein energy wasting.

Methods

This was a cross-sectional case–control study. Acylated and unacylated ghrelin and obestatin were measured in 42 children on conservative treatment (CT), 20 children on hemodialysis, 48 pediatric renal transplant (RTx) recipients and 43 controls (CTR) (mean age 11.9, range 5–20 years). Weight, height and bicipital, tricipital, subscapular and suprailiac folds were measured, and the body mass index-standard deviation score (BMI-SDS), percentage of fat mass and fat-free mass were calculated. Urea and creatinine were measured and the glomerular filtration rate (GFR) calculated.

Results

Unacylated ghrelin level was higher in patients than controls (p = 0.0001), with the highest levels found in hemodialysis patients (p = 0.001 vs. CKD-CT, p = 0.0001 vs. RTx, p < 0.0001 vs. CTR). Obestatin level was significantly higher in patients on hemodialysis than those on conservative treatment, RTx recipients and controls (p < 0.0001 in each case). Unacylated ghrelin negatively correlated with weight-SDS (p < 0.0001), BMI-SDS (p = 0.0005) and percentage fat mass (p = 0.004) and positively correlated with percentage fat-free mass (p = 0.004). Obestatin concentration negatively correlated with weight-SDS (p = 0.007). Unacylated ghrelin and obestatin concentrations positively correlated with creatinine and urea and inversely with eGFR, even after adjustments for gender, age, puberty and BMI-SDS (p < 0.0001 for each model).

Conclusions

Unacylated ghrelin and obestatin, negatively related to renal function, seem to be promising inverse indicators of nutritional status in children with CKD. Potential therapeutic implications in terms of optimization of their removal in patients on hemodialysis could be hypothesized.

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Acknowledgements

The authors wish to thank the patients who took part to the study and all the medical and nursing staff of the Pediatric Nephrology, Dialysis and Transplant Unit of IRCCS Ca′ Granda–Ospedale Maggiore Policlinico, Milan, Italy. Special thanks to Dr. Maria Rosa Grassi, who performed the nutritional evaluations.

Sources of support

This study was supported by the charity organization “Associazione del bambino nefropatico”.

Author information

Authors and Affiliations

  1. Division of Pediatrics, Department of Health Sciences, Università del Piemonte Orientale, V. Solaroli 17, 28100, Novara, Italy

    Alice Monzani, Flavia Prodam, Stefania Moia, Giulia Genoni, Anna Rapa & Gianni Bona

  2. Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione Cà Granda IRCCS, Ospedale Maggiore Policlinico, Milan, Italy

    Michela Perrone, Sara Testa, Fabio Paglialonga, Giovanni Montini & Alberto Edefonti

  3. Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy

    Giovanni Montini

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  1. Alice Monzani
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  2. Michela Perrone
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  3. Flavia Prodam
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  5. Giulia Genoni
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Contributions

AM, FlPr, GM and AE designed research; AM, MP, SM, ST and FaPa conducted research; AM, FlPr, GG and AR analyzed data; AM, GG, GB, GM and AE wrote the paper; AM had primary responsibility for final content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Giulia Genoni.

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Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

The study protocol was approved by the Ethics Committee of the Fondazione IRCCS Ca′ Granda–Ospedale Maggiore Policlinico, Milan, Italy (protocol number 396/2011 bis), and written informed consent was collected from the parents or legal guardians (and patients, where appropriate) of all children. All procedures were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Data

All data generated or analyzed during this study are included in this published article.

Additional information

This study is registered in the public trial registry www.clinicaltrials.com with the ID number NCT03171116.

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Monzani, A., Perrone, M., Prodam, F. et al. Unacylated ghrelin and obestatin: promising biomarkers of protein energy wasting in children with chronic kidney disease. Pediatr Nephrol 33, 661–672 (2018). https://doi.org/10.1007/s00467-017-3840-z

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