title: Inhibition of Sodium-Glucose Cotransporter 2 with Dapagliflozin in Han: SPRD Rats with Polycystic Kidney Disease.
abstract: OBJECTIVE
  Dapagliflozin (DAPA) is a selective inhibitor of the sodium-glucose cotransporter 2 (SGLT2) which induces glucosuria and osmotic diuresis. The therapeutic effect of DAPA in progressing stages of polycystic kidney disease (PKD) has not been studied.
  
  
  METHODS
  We examined the effect of DAPA in the Han: SPRD rat model of PKD. DAPA (10 mg/kg/day) or vehicle (VEH) was administered orally via gavage to 5 week old male Han: SPRD (Cy/+) or control (+/+) rats (n = 8-9 per group) for 5 weeks. Blood and urine were collected at baseline and after 2.5 and 5 weeks of treatment to assess renal function and albuminuria. At the end of the treatment, rats were sacrificed and kidneys were excised for histological analysis.
  
  
  RESULTS
  After 5 weeks of treatment, DAPA-treated Cy/+ and +/+ rats exhibited significantly higher glucosuria, water intake and urine output than VEH-treated rats. DAPA-treated Cy/+ rats also exhibited significantly higher clearances for creatinine and BUN and less albuminuria than VEH-treated Cy/+ rats. DAPA treatment for 5 weeks resulted in a significant increase of the kidney weight in Cy/+ rats but no change in cyst growth. The degree of tubular epithelial cell proliferation, macrophage infiltration and interstitial fibrosis was also similar in DAPA-and VEH-treated Cy/+ rats.
  
  
  CONCLUSIONS
  The induction of glucosuria with the SGLT2-specific inhibitor DAPA was associated with improved renal function and decreased albuminuria, but had no effect on cyst growth in Cy/+ rats. Overall the beneficial effects of DAPA in this PKD model were weaker than the previously described effects of the combined SGLT1/2 inhibitor phlorizin.
authors.affiliation: Division of Nephrology, University Hospital, Zx00FC;rich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rodriguez
authors.forename: Sarika
authors.initials: S
authors.lastname: Kapoor
authors.forename: Ilka
authors.initials: I
authors.lastname: Edenhofer
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
authors.forename: Meliana
authors.initials: M
authors.lastname: Riwanto
authors.forename: Anja
authors.initials: A
authors.lastname: Kipar
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Changlin
authors.initials: C
authors.lastname: Mei
authors.forename: Rudolf P
authors.initials: RP
authors.lastname: Wüthrich
mesh_terms: D000419:Albuminuria / Q000209:etiology; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D004231:Diuresis / Q000187:drug effects; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D006029:Glycosuria / Q000652:urine; D007668:Kidney / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D009929:Organ Size; D007690:Polycystic Kidney Diseases / Q000150:complications* / Q000473:pathology; D051381:Rats; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D014563:Urodynamics / Q000187:drug effects
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; C490300:Slc5a2 protein, rat; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C529054:dapagliflozin