Anti-Oxidant Therapy In Chronic Renal Insufficiency (ATIC) Study
Anti-Oxidant Therapy In Chronic Renal Insufficiency (ATIC) Study
The ATIC study is a randomised, double- blind, placebo-controlled trial in which the effects
 of oxidative stress-lowering treatment on vascular function and structure are studied in
 patients with chronic non-diabetic renal failure who are free from manifest arterial
 occlusive disease. Participants in the trial were randomised to active treatment consisting
 of add-on therapy with pravastatin, vitamin E and homocysteine-lowering therapy, or to
 placebo. Subjects not using angiotensin converting enzyme inhibitors (ACE-inhibitors) or
 angiotensin receptor blockers (ARBs) at inclusion were put on ACE-inhibitors for at least two
 weeks before the baseline measurement and randomisation. Those who were on ARBs continued
 their ARBs. We excluded individuals with diabetes mellitus (ADA criteria), active vasculitis,
 nephrotic syndrome (>3gr/24hr urine protein), renal transplantation, fasting total
 cholesterol > 7 mmol/L, cholesterol-lowering therapy within three months prior to inclusion
 or known ischemic cardiac, cerebrovascular or peripheral arterial disease. Ninety-three
 patients (out of 118 eligible patients) took part in the study and written informed consent
 was obtained from all participants.
Background: Patients with mild-to-moderate renal failure have an increased risk of
 cardiovascular disease (CVD), which is not fully explained by the presence of classical
 cardiovascular risk factors. Oxidative stress has been proposed to play a major role in the
 development of CVD among renal failure patients. We investigated, in patients with
 mild-to-moderate chronic kidney disease (CKD), the effect of an oxidative-stress-lowering
 therapy with pravastatin, vitamin E and homocysteine-lowering on carotid intima-media
 thickness and endothelial function (two strong surrogate markers of cardiovascular risk), and
 renal function.

 Methods: 93 patients with CKD (Cockcroft-Gault equation; mean: 41±17 ml / min per 1.73 m2)
 who were free of manifest arterial occlusive disease and diabetes mellitus were included in
 the Anti-oxidant Therapy In Chronic renal insufficiency (ATIC) study, a randomized,
 double-blind, placebo-controlled trial. The active treatment group received pravastatin 40
 mg/day to which after 6 months vitamin E 300 mg/day was added and after another 6 months
 homocysteine-lowering therapy (folic acid 5 mg/day, pyridoxine 100 mg, vitamin B-12 1
 mg/day). The placebo group received matching placebos at onset, and 6 and 12 months later.
 Blood pressure in both groups was managed according to a standard protocol to achieve a blood
 pressure of < 140/90 mmHg. Patients were followed up for two years. Measurements of common
 carotid artery intima-media thickness (CCA-IMT) and brachial artery endothelium-dependent,
 flow-mediated dilatation (BA-FMD) were performed at randomisation and after 6, 12 and 18
 months. Plasma oxidized LDL (oxLDL) and plasma malondialdehyde (MDA) were measured as markers
 of oxidative stress at randomisation and after 6, 12, 18 and 24 months. We used generalized
 estimating equations (GEE) for data analysis.
Inclusion Criteria:chronic

 -  kidney disease (clearence between 15-70ml/min)

 Exclusion Criteria:

 -  diabetes mellitus (ADA criteria), active vasculitis, nephrotic syndrome (>3g
 protein/24h urine), renal transplantation, fasting total cholesterol > 7 mmol/L,
 cholesterol-lowering therapy within three months prior to inclusion or known ischaemic
 coronary, cerebrovascular or peripheral arterial disease