4C: The Cardiovascular Comorbidity in Children With Chronic Kidney Disease Study

Sponsor

Heidelberg University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01046448

Collaborator

KfH Foundation for Preventive Medicine (Other), German Federal Ministry of Education and Research (Other)

650

Enrollment

Locations

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease Pediatric Cardiovascular Disease

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

650 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

The Cardiovascular Morbidity in Children With Chronic Renal Failure Study

Study Start Date :

Jul 1, 2009

Anticipated Primary Completion Date :

Apr 1, 2014

Anticipated Study Completion Date :

Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
4C Children with chronic kidney disease stage IIIb to V (GFR 10 to 45 ml/min/1.73m²) at screening.

Outcome Measures

Primary Outcome Measures

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 [3 years]

Secondary Outcome Measures

Genetic risk factors for early manifesting progressive vascular lesions and progressive kidney disease by the genome-wide SNP-screening and haplotype analysis. [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Medical University of Vienna	Vienna	Austria	1010
2	UZ Gent	Gent	Belgium	9000
3	University Hospital Motol	Prague	Czech Republic	15006
4	Service de Pédiatrie & Inserm U820	Lyon	France	69677
5	Hôpital de Hautepierre	Strasbourg	France	67098
6	Charité Children's Hospital	Berlin	Germany	13353
7	University Children's Hospital	Cologne	Germany	50937
8	University Children's Hospital	Erlangen	Germany	91054
9	University Children's Hospital	Essen	Germany	45122
10	Center for Pediatrics and Adolescent Medicine	Freiburg	Germany	79106
11	UKE University Children's Hospital	Hamburg	Germany	20246
12	Hannover Medical School	Hannover	Germany	30625
13	Center for Pediatrics and Adolescent Medicine	Heidelberg	Germany	69120
14	City Hospital St. Georg	Leipzig	Germany	04129
15	KfH Kidney Center for Children	Marburg	Germany	35043
16	University Children's Hospital	Münster	Germany	48149
17	Children's Hospital	Rostock	Germany	18057
18	Semmelweis University	Budapest	Hungary	1083
19	S. Orsola-Malphighi Hospital	Bologna	Italy	40123
20	Istituto Giannina Gaslini	Genova	Italy	16147
21	Fondazione OSP Maggiore Policlinico	Milano	Italy	20122
22	University of Padova	Padova	Italy	35128
23	Bambino Gesu	Rome	Italy	00163
24	Regina Margherita Children's Hospital	Torino	Italy	10126
25	Vilnius University Children's Hospital	Vilnius	Lithuania	08406
26	Medical University Gdansk	Gdansk	Poland	80211
27	University Children's Hospital	Krakow	Poland	30-663
28	Clinic of Pediatrics	Szczecin	Poland	71-344
29	Children's Memorial Health Institute	Warsaw	Poland	04-730
30	Hospital Sao Joao	Porto	Portugal	4200
31	University Children's Hospital	Belgrade	Serbia	11000
32	Karolinska University Hospital	Stockholm	Sweden	14186
33	Inselspital	Bern	Switzerland	3010
34	University Children's Hospital	Zurich	Switzerland	8032
35	Cukurova Universitesi	Adana	Turkey	01330
36	Ankara University of Medicine	Ankara	Turkey	06100
37	Hacettepe Medical Faculty	Ankara	Turkey	06100
38	Gazi University Hospital	Ankara	Turkey	06500
39	Baskent University, Faculty of Medicine	Ankara	Turkey
40	Diskapi Childrens Hospital	Ankara	Turkey
41	Sami Ulus Childrens Hospital	Ankara	Turkey
42	Cerrahpasa Tip Fakultesi	Istanbul	Turkey	34303
43	Istanbul Medical Faculty	Istanbul	Turkey	34360
44	Bakirkoy Children's Hospital	Istanbul	Turkey
45	Goztepe Educational and Research Hospital	Istanbul	Turkey
46	Haseki Educational and Research Hospital	Istanbul	Turkey
47	Marmara University Medical Faculty	Istanbul	Turkey
48	Sisli Educational and Research Hospital	Istanbul	Turkey
49	Ege University	Izmir	Turkey	35100
50	Great Ormond Street Hospital	London	United Kingdom	WC1N3JH

Sponsors and Collaborators

Heidelberg University
KfH Foundation for Preventive Medicine
German Federal Ministry of Education and Research

Investigators

Principal Investigator: Franz Schaefer, MD, Center for Pediatric and Adolescent Medicine, University of Heidelberg, Germany
Principal Investigator: Uwe Querfeld, MD, Klinik für Pädiatrie m.S. Nephrologie, Charite, 13353 Berlin, Germany