title: Development of albuminuria and enhancement of oxidative stress during chronic renin-angiotensin system suppression.
abstract: 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.
authors.affiliation: aUnidad de Hipertensión. Instituto de Investigación imas12. Hospital Universitario 12 de Octubre bInstituto Pluridisciplinar and Facultad de Farmacia, Universidad Complutense de Madrid cDepartamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid dDepartamento de Bioquímica, Facultad de Farmacia, Universidad Complutense de Madrid eDivision of Nephrology, Instituto de Investigación imas12, Hospital Universitario 12 de Octubre, Madrid, Spain *Gema Ruiz-Hurtado and Luis Miguel Ruilope contributed equally to the writing of this article.
authors.forename: Gema
authors.initials: G
authors.lastname: Ruiz-Hurtado
authors.forename: Luis
authors.initials: L
authors.lastname: Condezo-Hoyos
authors.forename: Helena
authors.initials: H
authors.lastname: Pulido-Olmo
authors.forename: Isabel
authors.initials: I
authors.lastname: Aranguez
authors.forename: Maria
authors.initials: M
authors.lastname: Del Carmen Gónzalez
authors.forename: Silvia
authors.initials: S
authors.lastname: Arribas
authors.forename: César
authors.initials: C
authors.lastname: Cerezo
authors.forename: Julián
authors.initials: J
authors.lastname: Segura
authors.forename: Manuel
authors.initials: M
authors.lastname: Praga
authors.forename: Maria S
authors.initials: MS
authors.lastname: Fernández-Alfonso
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Ruilope
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000175:diagnosis* / Q000209:etiology; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002374:Catalase / Q000097:blood; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D051436:Renal Insufficiency, Chronic / Q000150:complications; D012084:Renin-Angiotensin System / Q000187:drug effects*; D014527:Uric Acid / Q000097:blood
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D017382:Reactive Oxygen Species; D014527:Uric Acid; D008315:Malondialdehyde; D002374:Catalase