Clinical trial NCT01046448: The Cardiovascular Comorbidity in Children With Chronic Kidney Disease Study
Official title: The Cardiovascular Morbidity in Children With Chronic Renal Failure Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Kidney Disease
Pediatric
Cardiovascular Disease
Keywords: Children
chronic renal failure
chronic kidney disease
cardiovascular disease
cardiovascular morbidity
left ventricular hypertrophy
carotid intima media thickness
arterial stiffness
pulse wave velocity
augmentation index
left ventricular cardiac function
progression
genetic risk factors
vasculopathy
cardiopathy
whole genome analysis
haplotype analysis
SNP-screening
Lead sponsor: Heidelberg University
Sponsor class: OTHER
Collaborators: name: KfH Foundation for Preventive Medicine
name: German Federal Ministry of Education and Research
First posted: 2010-01-12
Enrollment: 650
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 650 children with CKD stage IIIb to V (GFR 10-45 ml/min/1.73m²). Children who reach end-stage renal disease will be continuously followed while on renal replacement therapy.

Brief summary: Children and adolescents with chronic kidney disease (CKD) are at high risk for cardiovascular (CV) morbidity and mortality. Recent studies suggest that pediatric patients with even moderately impaired kidney function may be afflicted with significant early cardiac and vascular abnormalities.

The pathogenesis and the natural course of CV comorbidity in pediatric CKD patients is still elusive. In this multicenter, prospective, observational study the prevalence, degree and progression of CV comorbidity in children will be characterized and related to CKD progression. The morphology and function of the heart and vessels will be monitored by sensitive, non-invasive methods and will be compared with aged matched healthy controls. Multiple potential clinical, anthropometric, biochemical, and pharmacological risk factors will be monitored prospectively and will be related to CV status. Genotyping might identify predisposing genetic factors for progression of CV comorbidity and underlying nephropathies.

Detailed description: Adult patients with CKD are at markedly increased risk of dying from cardiovascular events. The risk is most dramatically increased in young patients with end-stage renal disease, who are almost as likely to die from cardiovascular causes as elderly individuals in the general population.

Early morphological and functional vascular abnormalities can be detected even in adolescents with CKD, but information about the prevalence, severity and natural course of vascular lesions in different stages of renal failure is lacking and the factors predisposing to an early onset and rapid progression of cardiovascular morbidity are still elusive.

The pediatric population appears uniquely suited to study the effects of CKD on the cardiovascular system due to the virtual absence of vascular morbidity related to ageing, diabetes and smoking.

In order to improve our understanding of the causes and consequences of cardiovascular comorbidity in children with progressive CKD, a consortium of pediatric nephrologists in Europe has joined to perform a long-term prospective observational study following the cardiovascular health of children as they advance through successive stages of CKD.

The 4C Study will follow up at least 625 patients aged 6 to 17 years with a glomerular filtration rate of 10 to 45 ml/min/1.73 m² in more than 40 pediatric nephrology units in 14 European countries.

The morphology and function of the heart and the large arteries is regularly assessed by sensitive, non-invasive methods and the findings compared to a large group of healthy children.

Multiple potential clinical, anthropometric, biochemical, and pharmacological risk factors are monitored prospectively and will be related to the cardiovascular status of the patients.

A whole genome association study will be performed to identify genetic variants associated with the progression of cardio-vascular alterations and renal failure.

Eligibility criteria: Inclusion Criteria:

* Age 6 to 17 years
* GFR 10 to 45 ml/min/1.73m² (CKD stage IIIb to V);

Exclusion Criteria:

* Active systemic vasculitis
* Diabetes mellitus
* Renal vascular anomalies
* Anomalies of the limbs preventing standardized diagnostic procedures

Primary outcomes:
measure: Functional and morphological evidence of cardiovascular disease progression (arterial stiffness, myocardial dysfunction, cIMT, LVMI) and association with clinical, anamnestic, anthropometric, biochemical, drug-related and genetic risk factors
timeFrame: 3 years
Secondary outcomes:
measure: Genetic risk factors for early manifesting progressive vascular lesions and progressive kidney disease by the genome-wide SNP-screening and haplotype analysis.
timeFrame: 3 years
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Gent
country: Belgium
facility: UZ Gent
city: Prague
country: Czech Republic
facility: University Hospital Motol
city: Lyon
country: France
facility: Service de Pédiatrie & Inserm U820
city: Strasbourg
country: France
facility: Hôpital de Hautepierre
city: Berlin
country: Germany
facility: Charité Children's Hospital
city: Cologne
country: Germany
facility: University Children's Hospital
city: Erlangen
country: Germany
facility: University Children's Hospital
city: Essen
country: Germany
facility: University Children's Hospital
city: Freiburg
country: Germany
facility: Center for Pediatrics and Adolescent Medicine
city: Hamburg
country: Germany
facility: UKE University Children's Hospital
city: Hannover
country: Germany
facility: Hannover Medical School
city: Heidelberg
country: Germany
facility: Center for Pediatrics and Adolescent Medicine
city: Leipzig
country: Germany
facility: City Hospital St. Georg
city: Marburg
country: Germany
facility: KfH Kidney Center for Children
city: Münster
country: Germany
facility: University Children's Hospital
city: Rostock
country: Germany
facility: Children's Hospital
city: Budapest
country: Hungary
facility: Semmelweis University
city: Bologna
country: Italy
facility: S. Orsola-Malphighi Hospital
city: Genova
country: Italy
facility: Istituto Giannina Gaslini
city: Milano
country: Italy
facility: Fondazione OSP Maggiore Policlinico
city: Padova
country: Italy
facility: University of Padova
city: Rome
country: Italy
facility: Bambino Gesu
city: Torino
country: Italy
facility: Regina Margherita Children's Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Children's Hospital
city: Gdansk
country: Poland
facility: Medical University Gdansk
city: Krakow
country: Poland
facility: University Children's Hospital
city: Szczecin
country: Poland
facility: Clinic of Pediatrics
city: Warsaw
country: Poland
facility: Children's Memorial Health Institute
city: Porto
country: Portugal
facility: Hospital Sao Joao
city: Belgrade
country: Serbia
facility: University Children's Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Bern
country: Switzerland
facility: Inselspital
city: Zurich
country: Switzerland
facility: University Children's Hospital
city: Adana
country: Turkey
facility: Cukurova Universitesi
city: Ankara
country: Turkey
facility: Ankara University of Medicine
city: Ankara
country: Turkey
facility: Hacettepe Medical Faculty
city: Ankara
country: Turkey
facility: Gazi University Hospital
city: Ankara
country: Turkey
facility: Baskent University, Faculty of Medicine
city: Ankara
country: Turkey
facility: Diskapi Childrens Hospital
city: Ankara
country: Turkey
facility: Sami Ulus Childrens Hospital
city: Istanbul
country: Turkey
facility: Cerrahpasa Tip Fakultesi
city: Istanbul
country: Turkey
facility: Istanbul Medical Faculty
city: Istanbul
country: Turkey
facility: Bakirkoy Children's Hospital
city: Istanbul
country: Turkey
facility: Goztepe Educational and Research Hospital
city: Istanbul
country: Turkey
facility: Haseki Educational and Research Hospital
city: Istanbul
country: Turkey
facility: Marmara University Medical Faculty
city: Istanbul
country: Turkey
facility: Sisli Educational and Research Hospital
city: Izmir
country: Turkey
facility: Ege University
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
Study officials:
affiliation: Center for Pediatric and Adolescent Medicine, University of Heidelberg, Germany
name: Franz Schaefer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinik für Pädiatrie m.S. Nephrologie, Charite, 13353 Berlin, Germany
name: Uwe Querfeld, MD
role: PRINCIPAL_INVESTIGATOR
References: