title: Passive immunization against marinobufagenin attenuates renal fibrosis and improves renal function in experimental renal disease.
abstract: BACKGROUND
  We have shown that the cardiotonic steroid marinobufagenin (MBG) is elevated in clinical and experimental renal disease, and significantly contributes to the development of experimental uremic cardiomyopathy induced by removal of five-sixths of the kidney (5/6 nephrectomy; PNx) in the rat. We have demonstrated that both active and passive immunization against MBG with an anti-MBG monoclonal antibody (mAb 3E9) significantly attenuated cardiac fibrosis following PNx. In the present study we sought to determine whether the use of mAb 3E9 could improve renal function following PNx.
  
  
  METHODS
  Sprague-Dawley rats were treated with either mAb 3E9 or with DigiFab (an affinity-purified anti-digoxin antibody formerly named Digibind) during the fourth week after PNx. Sham-operated animals and PNx animals treated with an IgG antibody served as controls. Plasma, urine, and renal tissue were collected at the completion of the study to determine the effects of antibody treatment on renal function.
  
  
  RESULTS
  In PNx rats, treatments with mAb 3E9 and DigiFab, respectively, significantly reduced plasma creatinine, improved creatinine clearance, and reduced proteinuria below the values of these three measures in IgG-treated PNx controls. Additionally, treatment with mAb 3E9 and DigiFab significantly reduced renal fibrosis as measured with Western blotting and Sirius red/Fast green staining.
  
  
  CONCLUSIONS
  Passive immunization against MBG significantly improved renal function and markedly reduced renal fibrosis following the experimental induction of renal disease. The work in the study reported here adds to a growing body of knowledge implicating MBG in the development of chronic renal disease. Passive immunization against cardiotonic steroids may serve as a promising treatment for chronic renal disease.
authors.affiliation: Department of Medicine, University of Toledo, Toledo, Ohio;
authors.forename: Steven T
authors.initials: ST
authors.lastname: Haller
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Drummond
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yan
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.forename: Jiang
authors.initials: J
authors.lastname: Tian
authors.forename: Deepak
authors.initials: D
authors.lastname: Malhotra
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002018:Bufanolides / Q000276:immunology*; D002301:Cardiac Glycosides / Q000276:immunology; D005355:Fibrosis; D007116:Immunization, Passive; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D007668:Kidney; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000911:Antibodies, Monoclonal; D002018:Bufanolides; D002301:Cardiac Glycosides; D007140:Immunoglobulin Fab Fragments; C050199:digoxin antibodies Fab fragments; C093896:marinobufagenin
keywords: blood pressure; cardiotonic steroids; hypertension; marinobufagenin; renal disease; renal fibrosis.