title: Myeloperoxidase deficiency ameliorates progression of chronic kidney disease in mice.
abstract: Myeloperoxidase (MPO) is an enzyme expressed in neutrophils and monocytes/macrophages. Beside its well-defined role in innate immune defence, it may also be responsible for tissue damage. To identify the role of MPO in the progression of chronic kidney disease (CKD), we investigated CKD in a model of renal ablation in MPO knockout and wild-type mice. CKD was induced by 5/6 nephrectomy. Mice were followed for 10 wk to evaluate the impact of MPO deficiency on renal morbidity. Renal ablation induced CKD in wild-type mice with increased plasma levels of MPO compared with controls. No difference was found between MPO-deficient and wild-type mice regarding albuminuria 1 wk after renal ablation, indicating similar acute responses to renal ablation. Over the next 10 wk, however, MPO-deficient mice developed significantly less albuminuria and glomerular injury than wild-type mice. This was accompanied by a significantly lower renal mRNA expression of the fibrosis marker genes plasminogen activator inhibitor-I, collagen type III, and collagen type IV as well as matrix metalloproteinase-2 and matrix metalloproteinase-9. MPO-deficient mice also developed less renal inflammation after renal ablation, as indicated by a lower infiltration of CD3-positive T cells and F4/80-positive monocytes/macrophages compared with wild-type mice. In vitro chemotaxis of monocyte/macrophages isolated from MPO-deficient mice was impaired compared with wild-type mice. No significant differences were observed for mortality and blood pressure after renal ablation. In conclusion, these results demonstrate that MPO deficiency ameliorates renal injury in the renal ablation model of CKD in mice.
authors.affiliation: Division of Nephrology, Department of Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany;
authors.forename: Alexander
authors.initials: A
authors.lastname: Lehners
authors.affiliation: Division of Nephrology, Department of Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany;
authors.forename: Sascha
authors.initials: S
authors.lastname: Lange
authors.affiliation: Division of Nephrology, Department of Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany;
authors.forename: Gianina
authors.initials: G
authors.lastname: Niemann
authors.affiliation: Division of Nephrology, Department of Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany;
authors.forename: Alva
authors.initials: A
authors.lastname: Rosendahl
authors.affiliation: Division of Nephrology, Department of Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany;
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyer-Schwesinger
authors.affiliation: Division of Nephrology, Department of Pediatrics, University Hospital Hamburg-Eppendorf, Hamburg, Germany;
authors.forename: Jun
authors.initials: J
authors.lastname: Oh
authors.affiliation: Division of Nephrology, Department of Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany;
authors.forename: Rolf
authors.initials: R
authors.lastname: Stahl
authors.affiliation: Department of Physiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany;
authors.forename: Heimo
authors.initials: H
authors.lastname: Ehmke
authors.affiliation: Clinical Pharmacology, University of Halle, Halle, Germany; and.
authors.forename: Ralf
authors.initials: R
authors.lastname: Benndorf
authors.affiliation: Division of Cardiology, University of Cologne, Cologne, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Klinke
authors.affiliation: Division of Cardiology, University of Cologne, Cologne, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Baldus
authors.affiliation: Division of Nephrology, Department of Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany; wenzel@uke.de.
authors.forename: Ulrich Otto
authors.initials: UO
authors.lastname: Wenzel
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D008297:Male; D008661:Metabolism, Inborn Errors / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D009392:Nephrectomy; D009195:Peroxidase / Q000097:blood; D051436:Renal Insufficiency, Chronic / Q000473:pathology / Q000517:prevention & control*
chemical_list: D009195:Peroxidase
keywords: 5/6 nephrectomy; albuminuria; chronic kidney disease; glomerular sclerosis; myeloperoxidase