title: Aldosterone synthase gene polymorphism and renal histopathologic changes in kidney transplant patients receiving a calcineurin inhibitor.
abstract: BACKGROUND
  Aldosterone participates in the pathogenesis of calcineurin inhibitor nephrotoxicity (CIN), producing renal vasoconstriction and transforming growth factor beta (TGFß) expression. The objective of this study was to assess aldosterone polymorphisms and relationships to plasma aldosterone levels and the development of renal histological lesions in kidney transplant patients.
  
  
  METHODS
  Patients with kidney graft biopsy were divided according to the presence or absence of CIN. We determined aldosterone synthase (AS) -344 T/C and int 2 W/C gene polymorphisms and plasma aldosterone levels. Histological, biochemical and clinical variables were measured.
  
  
  RESULTS
  Calcineurin inhibitor (CI) levels were significantly higher in patients with the int 2 WW genotype than in patients with WC or CC genotypes. There was a greater degree of interstitial fibrosis in patients with int 2 CC genotype. No relationship was found between the different polymorphisms and a higher degree and/or frequency of CIN. There was also no relationship with plasma aldosterone levels.
  
  
  CONCLUSIONS
  The frequency of the different polymorphisms studied was not related to plasma aldosterone levels or the development of CIN; however, the int 2 CC genotype was related to a greater degree of interstitial fibrosis, whereas the WW genotype was related to higher CI serum levels.
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Ruiz-Palacios
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico.
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Rodríguez-Castellanos
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mancilla-Urrea
authors.affiliation: Department of Pathology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico.
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: Avila-Casado
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico.
authors.forename: Mónica X
authors.initials: MX
authors.lastname: Inofuentes-Rivero
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico.
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodriguez-Illana
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico.
authors.forename: José M
authors.initials: JM
authors.lastname: Fragoso
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico gvargas63@yahoo.com.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vargas-Alarcón
mesh_terms: D000293:Adolescent; D000328:Adult; D065095:Calcineurin Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005260:Female; D005355:Fibrosis / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D019405:Cytochrome P-450 CYP11B2