title: Oxidative stress, macrophage infiltration and CD163 expression are determinants of long-term renal outcome in macrohematuria-induced acute kidney injury of IgA nephropathy.
abstract: BACKGROUND
  Macroscopic hematuria (MH) may cause acute kidney injury (AKI) in IgA nephropathy. Up to 25% of patients with MH-associated AKI do not recover baseline renal function. Our objective was to identify subjects at high risk for an adverse renal function.
  
  
  METHODS
  We examined macrophages, oxidative stress markers (NADPH-p22 and HO-1) and the hemoglobin scavenger receptor (CD163) in renal biopsy specimens from 33 MH-AKI patients with complete recovery (CR, n = 17) or incomplete recovery (IR, n = 16) of renal function after 6.72 (range 0.5-21.5) years of follow-up.
  
  
  RESULTS
  CD163-expressing macrophages, HO-1 and NADPH-p22 expression were located in areas surrounding tubules with iron deposits and filled with erythrocyte casts. CD163-positive macrophages score and HO-1- and p22-positive staining correlated positively with percentage of tubules with erythrocyte casts and tubular necrosis. Macrophage infiltration, CD163-positive macrophage score, NADPH-p22- and HO-1-positive staining areas were significantly greater in IR patients when compared with CR patients. The CD163-positive macrophage score and oxidative stress markers (p22 and HO-1) were negatively correlated with renal function outcome, as determined by estimated glomerular filtration rate (eGFR) and proteinuria, at the end of the follow-up period. In multivariate analysis, the CD163-positive macrophage score remained significantly associated with final eGFR and proteinuria after adjustment by age, gender, duration of MH, initial eGFR and proteinuria.
  
  
  CONCLUSIONS
  Increased macrophage infiltration, CD163 expression and oxidative stress are significant prognostic factors for an IR of renal function in patients with MH-associated AKI. These molecular pathways may be involved in the renal response to injury and could be useful to improve diagnosis and therapeutics.
authors.affiliation: Department of Nephrology, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gutiérrez
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.forename: Alfonso
authors.initials: A
authors.lastname: Rubio-Navarro
authors.forename: Irene
authors.initials: I
authors.lastname: Buendía
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Blanco Colio
authors.forename: Oscar
authors.initials: O
authors.lastname: Toldos
authors.forename: Felix
authors.initials: F
authors.lastname: Manzarbeitia
authors.forename: Alberto
authors.initials: A
authors.lastname: de Lorenzo
authors.forename: Rosa
authors.initials: R
authors.lastname: Sanchez
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.forename: Manuel
authors.initials: M
authors.lastname: Praga
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Moreno
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D000704:Analysis of Variance; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002465:Cell Movement; D016009:Chi-Square Distribution; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000150:complications* / Q000473:pathology; D006417:Hematuria / Q000150:complications*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D011956:Receptors, Cell Surface / Q000378:metabolism; D020127:Recovery of Function; D018709:Statistics, Nonparametric; D013997:Time Factors; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; D051547:Heme Oxygenase-1; D019255:NADPH Oxidases; C086986:CYBA protein, human