The Effect of Childhood Dyslipidemia on Endothelial and Renal Function

Early Markers of Endothelial and Renal Dysfunction in Children With Dyslipidemia

The aim of the study is to assess if abnormal lipid levels in childhood could cause early damage of the inner layer of the vessels, the endothelium. Dysfunction of the endothelium is the first event in the development of atherosclerosis, is present at all stages of atherosclerosis and is potentially reversible in childhood. It has been suggested that dyslipidemia, via its detrimental effects on endothelium, could impair renal function. This study will assess the dysfunction of the kidneys in children with dyslipidemia.

Study Overview

• Status: Completed
• Conditions: Dyslipidemias; Endothelial Dysfunction; Children, Only; Renal Dysfunction; Hypercholesteremia in Children

Detailed Description

In children recruited in the study, family history of dyslipidemia or premature cardiovascular disease will be recorded. Furthermore, anthropometric and clinical characteristics will be noted and lipid measurements will be obtained at recruitment after a fasting period.

The investigators will test in children the flow-mediated dilation (FMD) which assesses the vasodilation due to the production of nitric oxide from the endothelium in response to occlusion-induced hyperaemia of the branchial artery and the carotid intima-media thickness (cIMT). These non-invasive ultrasound indices detect early vascular damage.

Renal function will be assessed in children with dyslipidemia by a new marker in serum, cystatin C, which is more accurate and reliable than creatinine. Also, creatinine serum levels and estimated glomerular filtration rate (eGFR) will be evaluated. Additionally, total protein, albumin, electrolyte and β2-microglobulin excretion in urine will be measured.

• Study Type: Observational
• Enrollment (Actual): 200

Contacts and Locations

Study Locations

• Greece
  • Ioánnina, Greece, 45500
    • University of Ioannina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 17 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The group of children with dyslipidemia will be selected from children referred to the Outpatient Lipid Clinic for Children and Adolescents and to the Pediatric Nephrology Department of the University Hospital of Ioannina. These are centers of excellence for assessing children with dyslipidemia and renal function in Northwestern Greece.

The referrals are due to abnormal lipid levels in routine blood samples or family history of dyslipidemia and/or family history of premature cardiovascular disease.

The group of controls will be selected from children attending the Outpatient Pediatric Clinic of University Hospital of Ioannina for follow-up of headache, heart murmur, constipation and loss of consciousness.

Description

Inclusion Criteria:

• Children and adolescents aged 7 to 17 years
• Dyslipidemia (serum levels of LDL-cholesterol ≥95th percentile or serum levels of triglycerides ≥95th percentile or serum levels of HDL-cholesterol ≤5th percentile for age and sex)

Exclusion Criteria:

• History of renal disease
• Dyslipidemia caused by nephrotic syndrome or chronic kidney disease
• Chronic use of medication
• Acute or chronic inflammatory process

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Dyslipidemia group; Children and adolescents with dyslipidemia
Control group; Children and adolescents without dyslipidemia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow-mediated dilation of the branchial artery	Non-invasive ultrasound assessment of endothelial function.	At subject enrollment
Carotid intima-media thickness	Non-invasive ultrasound assessment of early vascular disease.	At subject enrollment
Measurement of cystatin C in serum	Cystatin C is a marker for assessing renal function	At subject enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with abnormal levels of lipoprotein a.		At subject enrollment
Levels of β2-microglobulin in urine	Assessment of tubular function of the kidneys.	At subject enrollment
Serum creatinine levels	Assessment of renal function	At subject enrollment
Assessment of eGFR		At subject enrollment

Collaborators and Investigators

• Sponsor: University of Ioannina
• Collaborators: University Hospital, Ioannina

Publications and helpful links

General Publications

• Kosmeri C, Siomou E, Vlahos AP, Milionis H. Review shows that lipid disorders are associated with endothelial but not renal dysfunction in children. Acta Paediatr. 2019 Jan;108(1):19-27. doi: 10.1111/apa.14529. Epub 2018 Aug 22.
• Kosmeri C, Milionis H, Vlahos AP, Benekos T, Bairaktari E, Cholevas V, Siomou E. The impact of dyslipidemia on early markers of endothelial and renal dysfunction in children. J Clin Lipidol. 2021 Mar-Apr;15(2):292-300. doi: 10.1016/j.jacl.2020.12.003. Epub 2020 Dec 11.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2017
• Primary Completion (Actual): April 3, 2020
• Study Completion (Actual): April 3, 2020

Study Registration Dates

• First Submitted: February 20, 2019
• First Submitted That Met QC Criteria: February 26, 2019
• First Posted (Actual): February 27, 2019

Study Record Updates

• Last Update Posted (Actual): November 3, 2020
• Last Update Submitted That Met QC Criteria: November 2, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Renal Insufficiency; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: 234

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No