Effect of a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on carotid intima-media thickness, endothelial function, and renal function in patients with mild to moderate chronic kidney disease: results from the Anti-Oxidant Therapy in Chronic Renal Insufficiency (ATIC) Study.
BACKGROUND
Patients with chronic kidney disease have an increased risk of cardiovascular disease. Oxidative stress has been proposed to play a role in the development of cardiovascular disease among these patients.


METHODS
We conducted a randomized, double-blind trial in 93 patients (Cockcroft-Gault equation: creatinine clearance, 38+/-15 [mean+/-SD] mL/min per 1.73 m2 [0.63+/-0.25 mL/s per m2]) to investigate the effect of a treatment strategy designed primarily to achieve stepwise oxidative stress reduction on common carotid intima-media thickness (CC-IMT), brachial artery flow-mediated dilatation (BA-FMD), albuminuria, and renal function. The treatment group received a regimen of pravastatin to which vitamin E supplementation was added after 6 months and homocysteine-lowering therapy after another 6 months. Blood pressure in both groups was managed according to a standard protocol. The placebo group received matching placebos. Measurement of CC-IMT and BA-FMD was performed at randomization after 6, 12, and 18 months. Patients were followed up for 2 years. Generalized estimating equations were used for analysis.


RESULTS
Compared with placebo, active treatment was associated with a decrease in CC-IMT (after 18 months: from 0.68 to 0.63 mm in the treatment group and from 0.65 to 0.71 mm in the placebo group; P<.001), an increase in BA-FMD (after 18 months: from 4.66% to 7.56% in the treatment group and from 6.21% to 4.73% in the placebo group; P<.001), and an attenuated increase in urinary albumin excretion over time (P=.04 for between-group difference after 24 months), but no effect was observed on renal function.


CONCLUSIONS
In patients with mild to moderate chronic kidney disease, 18 months of a treatment strategy along with well-controlled blood pressure reduced CC-IMT and urinary albumin excretion and increased BA-FMD.


BACKGROUND
clinicaltrials.gov Identifier: NCT00384618.
Nanayakkara
Prabath W B
PW
Department of Internal Medicine, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, and Amphia Hospital, Breda, the Netherlands. p.nanayakkara@vumc.nl
van Guldener
Coen
C
ter Wee
Piet M
PM
Scheffer
Peter G
PG
van Ittersum
Frans J
FJ
Twisk
Jos W
JW
Teerlink
Tom
T
van Dorp
Wim
W
Stehouwer
Coen D A
CD
D000284:Administration, Oral; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging* / Q000503:physiopathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006710:Homocysteine / Q000037:antagonists & inhibitors* / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D017035:Pravastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D011736:Pyridoxine / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014463:Ultrasonography; D014810:Vitamin E / Q000008:administration & dosage / Q000627:therapeutic use*; D014815:Vitamins / Q000008:administration & dosage / Q000627:therapeutic use*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014815:Vitamins; D006710:Homocysteine; D014810:Vitamin E; D005492:Folic Acid; D011736:Pyridoxine; D017035:Pravastatin