BACKGROUND/AIMS: 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. CONCLUSION: 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.
BACKGROUND/AIMS: 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. CONCLUSION: 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: Harindra Rajasekeran; Heather N Reich; Michelle A Hladunewich; Daniel Cattran; Julie A Lovshin; Yuliya Lytvyn; Petter Bjornstad; Vesta Lai; Josephine Tse; Leslie Cham; Syamantak Majumder; Bridgit B Bowskill; M Golam Kabir; Suzanne L Advani; Ian W Gibson; Manish M Sood; Andrew Advani; David Z I Cherney Journal: Am J Physiol Renal Physiol Date: 2017-11-15
Authors: Carsten Bergmann; Lisa M Guay-Woodford; Peter C Harris; Shigeo Horie; Dorien J M Peters; Vicente E Torres Journal: Nat Rev Dis Primers Date: 2018-12-06 Impact factor: 52.329
Authors: Olha Kravtsova; Ruslan Bohovyk; Vladislav Levchenko; Oleg Palygin; Christine A Klemens; Timo Rieg; Alexander Staruschenko Journal: Am J Physiol Renal Physiol Date: 2022-04-25
Authors: Carmen Berghaus; Ann-Christin Groh; Davorka Breljak; Giuliano Ciarimboli; Ivan Sabolić; Hermann Pavenstädt; Thomas Weide Journal: Front Mol Biosci Date: 2022-02-16