Chronic kidney disease (CKD) is a prevalent disorder and a major health concern. Cardiovascular disease is the most prevailing and life-threatening complication observed in patients with CKD. The diagnosis of CKD places a patient at the highest cardiovascular risk level irrespective of the stage of renal decline. Therefore, fatal cardiovascular events are more likely to occur than the evolution to final stages of kidney disease with the need for dialysis. Counter intuitively, treatment of classical cardiovascular risk factors does not affect cardiovascular prognosis in CKD, which suggests that the missing link between these two entities has not been elucidated yet.

In the present project, the investigators focus on endothelial dysfunction in patients with CKD. Endothelial dysfunction precedes overt atherosclerotic changes by many years. In the absence of structural changes, endothelial dysfunction is still reversible, which offers therapeutic perspectives to tackle the progression towards atherosclerosis in an early stage.

The purpose of this study is to determine whether an exercise training program is effective in ameliorating endothelial dysfunction in patients with chronic kidney disease.

Inclusion Criteria:

• patients with CKD stage 3-4 (eGFR (15-59 ml/min/1.73m2) without cardiovascular disease.

Exclusion Criteria:

• patients < 18 years
• pregnancy
• warfarin therapy
• glucocorticoid therapy
• clinically active malignant disease
• heart failure (ejection fraction < 50%)
• peripheral vascular disease, defined as a history of intermittent claudication, abnormal peripheral angiography or Doppler ultrasound, lower limb artery bypass surgery/angioplasty/stenting or non-traumatic lower extremity amputation
• cerebrovascular disease, defined as a history of transient ischemic attack (TIA) or stroke, significant stenosis of the A. carotis on ultrasound/CT angiography or carotid endarterectomy/stenting
• coronary artery disease (CAD), defined as a history of myocardial infarction, coronary artery angioplasty/stenting/bypass surgery, significant structural coronary lesions on angiography or high suspicion of CAD on a maximal exercise test