title: Renoprotection by continuous erythropoietin receptor activator in puromycin aminonucleoside-induced nephrotic syndrome.
abstract: OBJECTIVE
  Recent studies have demonstrated that erythropoiesis-stimulating agents (ESAs) induce a tissue-protective effect in the kidney. In this study, we examined whether continuous erythropoietin receptor activator (CERA), a long-acting ESA, could prevent kidney injury, especially podocyte damage, in a rat model of nephrotic syndrome induced by puromycin aminonucleoside (PAN).
  
  
  METHODS
  Rats were injected with CERA (30 µg/kg) or vehicle 4 h before the injection of PAN (50 mg/kg). Renal function, kidney injury, and podocyte damage were assessed at 7 days.
  
  
  RESULTS
  The levels of proteinuria, BUN, and plasma creatinine significantly increased in rats with PAN-induced nephrosis. Treatment with CERA significantly prevented these deteriorations induced by PAN. Glomerular lesions, especially vacuolation of podocytes, and the increase of desmin expression in PAN-treated rats were significantly ameliorated by treatment with CERA. Treatment with CERA also significantly prevented the decrease in the protein productions of nephrin and podocin in the kidneys of PAN-treated rats. We found persistent activation of the Akt signaling pathway in the kidneys of CERA-treated rats.
  
  
  CONCLUSIONS
  CERA could ameliorate renal dysfunction in PAN-induced nephrosis, which might be due to the amelioration of podocyte injury. CERA inhibited the depletion of nephrin and podocin, key components of the glomerular filtration barrier, and alleviated proteinuria. Activation of the Akt signaling pathway might be involved in the renoprotective effect of CERA.
authors.affiliation: Product Research Department, Chugai Pharmaceutical Co., Ltd, Gotemba, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Aizawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeda
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Tashiro
authors.forename: Keigo
authors.initials: K
authors.lastname: Yorozu
authors.forename: Michinori
authors.initials: M
authors.lastname: Hirata
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kanada
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Moriguchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Endo
mesh_terms: D000818:Animals; D004921:Erythropoietin / Q000627:therapeutic use*; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000517:prevention & control*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011692:Puromycin Aminonucleoside; D051381:Rats; D017208:Rats, Wistar
chemical_list: C508420:continuous erythropoietin receptor activator; D004921:Erythropoietin; D011092:Polyethylene Glycols; D011692:Puromycin Aminonucleoside