title: Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression.
abstract: BACKGROUND
  Hypertension is a multi-factorial disease of increasing prevalence and a major risk factor for cardiovascular mortality even in the presence of adequate treatment. Progression of cardiovascular disease (CVD) occurs frequently during chronic renin-angiotensin-system (RAS) suppression, and albuminuria is a marker of CV risk. High prevalence of albuminuria in treated hypertensive patients has been demonstrated, but there are no available markers able to predict evolution. The aim of this study was the identification of novel indicators of albuminuria progression measurable in urine of diabetic and non-diabetic patients.
  
  
  METHODS
  1143 hypertensive patients under chronic treatment were followed for a minimum period of 3 years. Among them, 105 diabetic and non-diabetic patients were selected and classified in three groups according to albuminuria development during follow-up: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Differential urine analysis was performed by 2D gel electrophoresis (2D-DIGE) and further confirmed by liquid chromatography-mass spectrometry. Non-parametric statistical tests were applied.
  
  
  RESULTS
  CD59 glycoprotein and alpha-1 antitrypsin (AAT) resulted already altered in patients developing albuminuria de novo, with a similar response in those with maintained albuminuria. A prospective study in a sub-group of normoalbuminuric patients who were clinically followed up for at least 1 year from urine sampling, revealed CD59 and AAT proteins significantly varied in the urine collected from normoalbuminurics who will negatively progress, serving as predictors of future albuminuria development.
  
  
  CONCLUSIONS
  CD59 and AAT proteins are significantly altered in hypertensive patients developing albuminuria. Interestingly, CD59 and AAT are able to predict, in normoalbuminuric individuals, who will develop albuminuria in the future, being potential predictors of vascular damage and CV risk. These findings contribute to early identify patients at risk of developing albuminuria even when this classical predictor is still in the normal range, constituting a novel strategy towards a prompt and more efficient therapeutic intervention with better outcome.
authors.affiliation: Departamento de Inmunologia, Laboratorio de Inmunoalergia y Proteomica, IIS-Fundacion Jimenez Diaz, UAM, REDinREN, Avda Reyes Catolicos 2, 28040, Madrid, Spain. laura.gcalero@fjd.es.
authors.forename: Laura
authors.initials: L
authors.lastname: Gonzalez-Calero
authors.affiliation: Departamento de Inmunologia, Laboratorio de Inmunoalergia y Proteomica, IIS-Fundacion Jimenez Diaz, UAM, REDinREN, Avda Reyes Catolicos 2, 28040, Madrid, Spain. marta.martin@fjd.es.
authors.forename: Marta
authors.initials: M
authors.lastname: Martin-Lorenzo
authors.affiliation: Laboratorio de Fisiopatologia Vascular, Hospital Nacional de Paraplejicos SESCAM, Toledo, Spain. ferdela@sescam.jccm.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: de la Cuesta
authors.affiliation: Departamento de Inmunologia, Laboratorio de Inmunoalergia y Proteomica, IIS-Fundacion Jimenez Diaz, UAM, REDinREN, Avda Reyes Catolicos 2, 28040, Madrid, Spain. asanzmaroto@gmail.com.
authors.forename: Aroa S
authors.initials: AS
authors.lastname: Maroto
authors.affiliation: Laboratorio de Fisiopatologia Vascular, Hospital Nacional de Paraplejicos SESCAM, Toledo, Spain. m_baldan@msn.com.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baldan-Martin
authors.affiliation: Unidad de Hipertension, Instituto de Investigacion i + 12, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, 28041, Madrid, Spain. gemainfantes@yahoo.es.|Instituto Pluridisciplinar, Universidad Complutense de Madrid, Madrid, Spain. gemainfantes@yahoo.es.
authors.forename: Gema
authors.initials: G
authors.lastname: Ruiz-Hurtado
authors.affiliation: Unidad de Hipertension, Instituto de Investigacion i + 12, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, 28041, Madrid, Spain. helena_p_87@hotmail.com.
authors.forename: Helena
authors.initials: H
authors.lastname: Pulido-Olmo
authors.affiliation: Unidad de Hipertension, Instituto de Investigacion i + 12, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, 28041, Madrid, Spain. hta@juliansegura.com.
authors.forename: Julian
authors.initials: J
authors.lastname: Segura
authors.affiliation: Laboratorio de Fisiopatologia Vascular, Hospital Nacional de Paraplejicos SESCAM, Toledo, Spain. megonzalezb@sescam.jccm.es.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Barderas
authors.affiliation: Unidad de Hipertension, Instituto de Investigacion i + 12, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, 28041, Madrid, Spain. ruilope@ad-hocbox.com.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Ruilope
authors.affiliation: Departamento de Inmunologia, Laboratorio de Inmunoalergia y Proteomica, IIS-Fundacion Jimenez Diaz, UAM, REDinREN, Avda Reyes Catolicos 2, 28040, Madrid, Spain. fvivanco@fjd.es.|Departamento de Bioquimica y Biologia Molecular I, Universidad Complutense de Madrid, Madrid, Spain. fvivanco@fjd.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: Vivanco
authors.affiliation: Departamento de Inmunologia, Laboratorio de Inmunoalergia y Proteomica, IIS-Fundacion Jimenez Diaz, UAM, REDinREN, Avda Reyes Catolicos 2, 28040, Madrid, Spain. galvarez@fjd.es.
authors.forename: Gloria
authors.initials: G
authors.lastname: Alvarez-Llamas
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology / Q000652:urine; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D018957:CD59 Antigens / Q000652:urine*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology / Q000652:urine; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods; D012084:Renin-Angiotensin System / Q000187:drug effects*; D018570:Risk Assessment; D012307:Risk Factors; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D016482:Urinalysis; D000515:alpha 1-Antitrypsin / Q000652:urine*
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D018957:CD59 Antigens; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin; C051590:CD59 protein, human