title: Tubular injury as a cardinal pathologic feature in human heme oxygenase-1 deficiency.
abstract: Heme oxygenase (HO) catalyzes degradation of heme to biliverdin, iron, and carbon monoxide. It consists of three isoforms: an inducible form (HO-1), a constitutive form (HO-2), and the third isoform (HO-3), with properties similar to HO-2. There is limited evidence to suggest that the induction of HO-1 may have anti-inflammatory effects in an in vivo model of oxidative stress-mediated renal injury. We experienced the first human case of HO-1 deficiency. The patient had persistent proteinuria and hematuria, with biochemical evidence of renal tubular injury. We obtained three consecutive renal specimens: two from renal biopsies at 2 and 5 years of age and the third from autopsy at 6 years of age. The patient had systemic vascular endothelial-cell injury with massive intravascular hemolysis. The serum was loaded with heme and a large amount of heme-conjugated haptoglobin. A high concentration of haptoglobin was also detectable in urine. Mesangial proliferation or change in glomerular capillary-wall thickness was relatively mild to moderate in all specimens. Electron microscopic examination showed widespread endothelial detachment and subendothelial deposits of an unidentifiable material. It was striking that tubulointerstitial injury, with tubular dilatation and/or atrophy, interstitial fibrosis, and inflammatory cell infiltration, advanced progressively. Tubular epithelial cells were injured, and massive deposition of iron and haptoglobin was detectable. Bowman's capsules were dilated significantly, probably secondary to the collapse of atrophic tubuli. This is the first report to show that HO-1 has critical roles in vivo in protecting renal tubuli, in addition to vascular endothelium, from oxidative injury.
authors.affiliation: Department of Pediatrics and Division of Blood Purification, School of Medicine, Kanazawa University, Japan. kohta@med.kanazawa-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Ohta
authors.forename: A
authors.initials: A
authors.lastname: Yachie
authors.forename: K
authors.initials: K
authors.lastname: Fujimoto
authors.forename: H
authors.initials: H
authors.lastname: Kaneda
authors.forename: T
authors.initials: T
authors.lastname: Wada
authors.forename: T
authors.initials: T
authors.lastname: Toma
authors.forename: A
authors.initials: A
authors.lastname: Seno
authors.forename: Y
authors.initials: Y
authors.lastname: Kasahara
authors.forename: H
authors.initials: H
authors.lastname: Yokoyama
authors.forename: H
authors.initials: H
authors.lastname: Seki
authors.forename: S
authors.initials: S
authors.lastname: Koizumi
mesh_terms: D002675:Child, Preschool; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000172:deficiency*; D051547:Heme Oxygenase-1; D006801:Humans; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins
chemical_list: D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1