Oxidative stress plays an important role in causing progressive kidney disease. However, it is not known if the oxidative stress and the proinflammatory state of the kidney can be favorably influenced without the reduction in blood pressure or improvement in proteinuria. We examined the influence of add-on angiotensin II receptor blockade administered as losartan 50 mg per day for one month on the oxidative stress and proinflammatory state of the kidney in patients with chronic kidney disease (CKD). All subjects were taking an angiotensin converting-enzyme inhibitor, lisinopril 40 mg per day in addition to other antihypertensive agents. Oxidative stress to lipids and proteins was measured by a HPLC assay for malondialdheyde and carbonyl concentration respectively. In addition, oxidative stress to proteins was measured by western blotting of urinary and plasma proteins after derivatizing with dinitrophenylhydrazine. Urinary inflammation was measured by MCP-1 excretion rate. Sixteen patients (10 Blacks, 6 Whites; 14 males), of average age 53 ± 9 years completed the trial. The etiology of CKD was Type 2 diabetes mellitus in 12 and glomerulonephritis in the remaining. Seated BP at baseline was 156 ± 18/88 ± 12 mm Hg requiring 3.13 ± 1.2 antihypertensive drugs, creatinine was 2.0 ± 0.8 mg/dL and proteinuria 3.6 ± 0.71 g/g creatinine/24 hours. There was no change in proteinuria or 24 hour ambulatory blood pressure with add-on angiotensin II receptor blockade with losartan therapy. Prior to losartan, urinary protein oxidation was 99% higher compared to plasma (p=0.008). Urinary albumin oxidation was 71% higher than plasma albumin (p=0.045). There was a 35% reduction in urinary albumin oxidative state with add-on losartan therapy (p=0.036). Urine malondialdehyde and plasma MDA were elevated compared to age matched controls. Urinary MDA was significantly reduced from 4.75 ± 3.23 µmol/g creatinine to 3.39 ± 2.17 µmol/g creatinine with add-on losartan therapy. However, plasma malondialdehyde or plasma oxidized proteins did not change in response to additional angiotensin II blockade. A good correlation was seen between change in urinary oxidized albumin and urinary MCP-1 level (r=0.61, p=0.012). These data demonstrate that oxidant damage to urinary protein and lipids can be reduced with additional angiotensin II receptor blockade, independent of reductions in proteinuria or blood pressure. Urinary measurements of markers of oxidative damage, both protein carbonyls and lipid hydroperoxides are more sensitive than plasma measurements in patients with CKD. The significant association of the change in MCP1 in the urine with reduction in oxidative stress supports experimental data in animals that demonstrate the important role of the redox state in the kidney with renal fibrosis and progressive kidney damage.