title: Expression of age-related factors during the development of renal damage in patients with IgA nephropathy.
abstract: BACKGROUND
  Chronic kidney disease patients share clinical and pathological features with the general aging population. Increased oxidative DNA damage, accumulation of cell cycle-arrested cells and decreased Klotho expression are assumed to be age-related factors that are reportedly linked to kidney disease. This study sought to determine the association between these age-related factors and renal damage in patients with IgA nephropathy (IgAN).
  
  
  METHODS
  We performed a cross-sectional analysis of 71 patients who were diagnosed with IgAN by renal biopsy. Expression of 8-hydroxydeoxyguanosine (8-OHdG, a marker of oxidative DNA damage), p16 (a marker of cell cycle-arrest) and Klotho (an anti-aging protein) were evaluated by immunohistochemical staining of renal biopsy samples. We correlated the changes in expression of these markers with Lee's pathologic grades and the Oxford classification. We also investigated the independent association between these markers and interstitial fibrosis using multiple linear regression analysis.
  
  
  RESULTS
  8-OHdG and p16 increased but Klotho decreased with progression of pathologic grade. Expression of 8-OHdG and p16 increased with the deterioration of mesangial hypercellularity and segmental glomerulosclerosis. In addition, p16 increased but Klotho decreased with progression of tubular atrophy/interstitial fibrosis. In univariate regression analysis, age, body mass index, systolic blood pressure, urinary protein excretion and expression of 8-OHdG, p16 and Klotho showed significant correlations with interstitial fibrosis. Multivariable regression analyses revealed that aging, increased renal expression of p16 and decreased expression of Klotho were independently correlated with interstitial fibrosis.
  
  
  CONCLUSIONS
  The age-related factors might play important roles in the development of IgAN.
authors.affiliation: Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. sdoi@hiroshima-u.ac.jp.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Doi
authors.affiliation: Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Department of Regeneration and Medicine, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Nakashima
authors.affiliation: Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kawaoka
authors.affiliation: Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Doi
authors.affiliation: Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yokoyama
authors.affiliation: Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Arihiro
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
authors.affiliation: Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Masaki
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000375:Aging / Q000473:pathology; D059447:Cell Cycle Checkpoints; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D005922:Glomerulonephritis, IGA / Q000473:pathology*; D005966:Glucuronidase / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000473:pathology*; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005966:Glucuronidase; D000090265:Klotho Proteins; D003849:Deoxyguanosine
keywords: Aging; Cell cycle arrest; IgA nephropathy; Klotho; Oxidative DNA damage