Renal effects of long-term darbepoetin alpha treatment in hypertensive TGR(mRen2)27 rats

Anne-Roos S. Frenay*, Willem-Peter T. Ruifrok, Marian Bulthuis, Sippie Huitema, Rudolf A. de Boer, Harry van Goor

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
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Abstract

Introduction: 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.

Materials and 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-3 alpha 1 and kidney injury molecule-1 (KIM-1).

Results: DA had no effect on SBP, serum creatinine and proteinuria. Interstitial and glomerular alpha-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 alpha-SMA and KIM-1 expression.

Conclusion: 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.

Original languageEnglish
Pages (from-to)232-238
Number of pages7
JournalJournal of the Renin-Angiotensin-Aldosterone System
Volume13
Issue number2
DOIs
Publication statusPublished - Jun-2012

Keywords

  • ACEi
  • darbepoetin alpha
  • hypertension
  • kidney
  • renin-angiotensin system
  • Ren2
  • ERYTHROPOIETIN PROTECTS
  • HOMOZYGOUS TGR(MREN2)27
  • BLOOD-PRESSURE
  • KIDNEY INJURY
  • MAP-KINASE
  • CELL-DEATH
  • FAILURE
  • PROGRESSION
  • ISCHEMIA
  • BLOCKADE

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