Development of albuminuria and enhancement of oxidative stress during chronic renin-angiotensin system suppression

Objective: Albuminuria has been recently described in hypertensive patients under chronic renin-angiotensin system (RAS) suppression. We investigated whether this fact could be related to an increase in oxidative stress. Methods: We examined normoalbuminuric and albuminuric patients in stage 2 chronic kidney disease, both with more than 2 years of RAS blockade. The relationship between albuminuria and circulating biomarkers for both oxidative damage, that is carbonyl and malondialdehyde, as well as antioxidant defense, that is reduced glutathione, thiol groups, uric acid, bilirubin, or catalase, and superoxide scavenging activity, was assessed. Results: We found that only patients with albuminuria showed an important increase in carbonyls (P < 0.001) and malondialdehyde (P < 0.05) compared to normoalbuminuric patients. This increase in oxidative damage was also accompanied by a rise in catalase activity (P < 0.05) and low-molecular-weight antioxidants only when they were measured as total antioxidant capacity (P < 0.01). In order to establish the specific oxidative status of each group, new indexes of oxidative damage and antioxidant defense were calculated with all these markers following a mathematical and statistical approach. Although both pro-oxidant and antioxidant indexes were significantly increased in patients with albuminuria, only the oxidative damage index positively correlated with the increase of albumin/creatinine ratio (P = 0.0024). Conclusions: We conclude that albuminuria is accompanied by an amplified oxidative damage in patients in early stages of chronic kidney disease. These results indicate that chronic RAS protection must be directed to avoid development of albuminuria and oxidative damage.