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The effect of a multidisciplinary weight loss program on renal circadian rhythm in obese adolescents

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Abstract

Adolescent obesity is a serious health problem associated with many comorbidities. Obesity-related alterations in circadian rhythm have been described for nocturnal blood pressure and for metabolic functions. We believe renal circadian rhythm is also disrupted in obesity, though this has not yet been investigated. This study aimed to examine renal circadian rhythm in obese adolescents before and after weight loss.

In 34 obese adolescents (median age 15.7 years) participating in a residential weight loss program, renal function profiles and blood samples were collected at baseline, after 7 months, and again after 12 months of therapy. The program consisted of dietary restriction, increased physical activity, and psychological support. The program led to a median weight loss of 24 kg and a reduction in blood pressure. Initially, lower diurnal free water clearance (− 1.08 (− 1.40–− 0.79) mL/min) was noticed compared with nocturnal values (0.75 (− 0.89–− 0.64) mL/min). After weight loss, normalization of this inverse rhythm was observed (day − 1.24 (− 1.44–1.05) mL/min and night − 0.98 (− 1.09–− 0.83) mL/min). A clear circadian rhythm in diuresis rate and in renal clearance of creatinine, solutes, sodium, and potassium was seen at all time points. Furthermore, we observed a significant increase in sodium clearance. Before weight loss, daytime sodium clearance was 0.72 mL/min (0.59–0.77) and nighttime clearance was 0.46 mL/min (0.41–0.51). After weight loss, daytime clearance increased to 0.99 mL/min (0.85–1.17) and nighttime clearance increased to 0.78 mL/min (0.64–0.93).

Conclusion: In obese adolescents, lower diurnal free water clearance was observed compared with nocturnal values. Weight loss led to a normalization of this inverse rhythm, suggesting a recovery of the anti-diuretic hormone activity. Both before and after weight loss, clear circadian rhythm of diuresis rate and renal clearance of creatinine, solutes, sodium, and potassium was observed.

What is Known:

• Obesity-related alterations in circadian rhythm have been described for nocturnal blood pressure and for metabolic functions. We believe renal circadian rhythm is disrupted in obesity, though this has not been investigated yet.

What is New:

• In obese adolescents, an inverse circadian rhythm of free water clearance was observed, with higher nighttime free water clearance compared with daytime values. Weight loss led to a normalization of this inverse rhythm, suggesting a recovery of the anti-diuretic hormone activity.

• Circadian rhythm in diuresis rate and in the renal clearance of creatinine, solutes, sodium, and potassium was preserved in obese adolescents and did not change after weight loss.

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Abbreviations

ACE:

Angiotensin-converting enzyme

ADH:

Anti-diuretic hormone

AGT:

Angiotensinogen

AngII:

Angiotensin II

BMI:

Body mass index

BP:

Blood pressure

BSA:

Body surface area

DM:

Diabetes mellitus

eGFR:

Estimated glomerular filtration rate

FWC:

Free water clearance

GFR:

Glomerular filtration rate

RAAS:

Renin-angiotensin-aldosterone system

RFP:

Renal function profile

RPF:

Renal plasma flow

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Funding

Kim Pauwaert has received research grants from Ferring Pharmaceuticals.

Elke Bruneel has received research grants from Ferring Pharmaceuticals.

Johan Vande Walle has received consulting fees and travel reimbursements from Ferring Pharmaceuticals and payment for lectures from Ferring Pharmaceuticals and Astellas Pharma.

Karel Everaert has received research grants and payment for lectures all in contract with his institution from Ferring Pharmaceuticals, Medtronic and Astellas Pharma.

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Author notes

  1. Kim Pauwaert and Sarah Dejonckheere contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium

    Kim Pauwaert, Elke Bruneel, Jolien Van Der Jeugt, Saskia Roggeman & Karel Everaert

  2. Department of Pediatric Nephrology, Ghent University Hospital, Ghent, Belgium

    Sarah Dejonckheere, Ann De Guchtenaere & Johan Vande Walle

  3. Faculty of Medicine, Ghent University, Ghent, Belgium

    Sarah Dejonckheere & Laura Keersmaekers

  4. Medical Pediatric Rehabilitation Center, Zeepreventorium, De Haan, Belgium

    Ann De Guchtenaere

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Contributions

Kim Pauwaert had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Vande Walle, Everaert, De Guchtenaere

Acquisition of data: Dejonckheere, Bruneel, Keersmaeckers, De Guchtenaere

Database work-up: Pauwaert, Dejonckheere, Bruneel, Van der Jeugt

Statistical analysis: Pauwaert, Dejonckheere, Bruneel, Keersmaeckers

Drafting of the manuscript: Pauwaert, Dejonckheere

Critical revision of the manuscript for important intellectual content: Everaert, Vande Walle, Roggeman, De Guchtenaere

Corresponding author

Correspondence to Kim Pauwaert.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ghent University Hospital review board (EC 2015/1438). The Declaration of Helsinki was followed and conducted in accordance with the legal regulations in Belgium.

Informed consent

Informed consent was obtained from all individual participants and their parents included in the study.

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Communicated by Mario Bianchetti

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Pauwaert, K., Dejonckheere, S., Bruneel, E. et al. The effect of a multidisciplinary weight loss program on renal circadian rhythm in obese adolescents. Eur J Pediatr 178, 1849–1858 (2019). https://doi.org/10.1007/s00431-019-03456-y

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