Urinary measurements of markers of oxidative stress
and damage to lipids and proteins appear to be more sensitive than plasma measurements in patients with
8. Agarwal, R. JOURNAL NAME- Am J Physiol Renal Physiol VOL.
284 2003 Apr PP. F863-9 DOCUMENT TYPE- Clinical Trial; Journal Article; Randomized Controlled Trial JOURNAL
CODE- 100901990 ISSN- 0363-6127 CORPORATE AUTHOR- Indiana University School of Medicine and Richard L.
Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana 46202, USA. email@example.com PUBLICATION
COUNTRY- United States LANGUAGE- English Oxidative stress plays an important role in causing progressive
chronic kidney disease (CKD). We examined the influence of add-on ANG II receptor blockade administered as
losartan (50 mg/day for 1 mo) on oxidative stress and proinflammatory state of the kidney in patients with
CKD. All subjects were taking an angiotensin-converting enzyme inhibitor plus other antihypertensive agents.
Oxidative stress to lipids and proteins was measured by an HPLC assay for malondialdehyde (MDA) and carbonyl
concentration, respectively. Urinary inflammation was measured by monocyte chemotactic protein-1 (MCP-1)
excretion rate. The etiology of CKD was type 2 diabetes mellitus in 12 and glomerulonephritis in 4 patients.
There was no change in proteinuria or 24-h ambulatory blood pressure (BP) with add-on ANG II receptor blockade
with losartan therapy. Before losartan therapy, urinary protein and albumin oxidation were 99 and 71% higher,
respectively, compared with in plasma (P 60 0.05). There was a 35% reduction in urinary oxidized albumin with
add-on losartan therapy (P = 0.036). Urinary and plasma MDA were elevated compared with age-matched controls.
Urinary MDA was significantly reduced from 4.75 +/- 3.23 to 3.39 +/- 2.17 micromol/g creatinine with add-on
losartan therapy. However, plasma MDA or oxidized proteins did not change in response to additional ANG II
blockade. A good correlation was seen between the change in urinary oxidized albumin and MCP-1 levels (r =
0.61, P = 0.012). These data demonstrate that oxidative damage to urinary protein and lipids can be reduced
with additional ANG II receptor blockade, independently of reductions in proteinuria or BP. Urinary
measurements of markers of oxidative damage to lipids and proteins appear to be more sensitive than plasma
measurements in patients with CKD. The significant association of the change in urinary MCP-1 with a reduction
in oxidative stress supports the role of the redox state in the kidney with renal fibrosis and progressive
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to Free Radical Laboratory Validation 1.