title: Renal effects of long-term darbepoetin alpha treatment in hypertensive TGR(mRen2)27 rats.
abstract: BACKGROUND
  Erytropoietin (EPO) has cytoprotective and angiogenic properties and has a beneficial effect in ischaemic conditions. Since the development of renal interstitial abnormalities are often associated with ischaemia, we studied the effects of the long-acting EPO analogue darbepoetin alpha (DA) on kidney damage in TGR(mRen2)27 (Ren2) rats.
  
  
  METHODS
  Ren2 rats were randomised to DA or vehicle (VEH) or to DA + angiotensin converting enzyme inhibitor (ACEi) or VEH + ACEi. Sprague Dawley (SD) rats served as controls. Blood pressure was measured weekly and 24-h urine was collected to measure proteinuria. Blood samples were collected for creatinine and haematocrit. Kidneys were studied for inflammation and pre-fibrosis. Renal mRNA expression was studied for EPO, EPO-receptor, collagen-3α1 and kidney injury molecule-1 (KIM-1).
  
  
  RESULTS
  DA had no effect on SBP, serum creatinine and proteinuria. Interstitial and glomerular α-SMA expression was significantly increased in Ren2. ACEi but not DA improved the increased renal inflammatory and pro-fibrotic profile in Ren2 rats. DA on top of ACEi further reduced glomerular α-SMA and KIM-1 expression.
  
  
  CONCLUSIONS
  Long-term DA treatment has no beneficial effects on renal structural and functional changes in TGR(mRen2)27 rats in the time frame studied and the dose provided.
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands. a.s.frenay@umcg.nl
authors.forename: Anne-Roos S
authors.initials: AR
authors.lastname: Frenay
authors.forename: Willem-Peter T
authors.initials: WP
authors.lastname: Ruifrok
authors.forename: Marian
authors.initials: M
authors.lastname: Bulthuis
authors.forename: Sippie
authors.initials: S
authors.lastname: Huitema
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D000068256:Darbepoetin alfa; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D024061:Collagen Type III; D000068256:Darbepoetin alfa; D004921:Erythropoietin; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; C110936:Havcr1 protein, rat; C498862:Acta2 protein, rat