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.

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.

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

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.