Dapagliflozin in focal segmental glomerulosclerosis: a combined human-rodent pilot study

DOI Web Site 被引用文献1件
  • Harindra Rajasekeran
    Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Heather N. Reich
    Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Michelle A. Hladunewich
    Department of Medicine, Division of Nephrology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
  • Daniel Cattran
    Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Julie A. Lovshin
    Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Yuliya Lytvyn
    Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Petter Bjornstad
    Department of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, Colorado
  • Vesta Lai
    Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Josephine Tse
    Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Leslie Cham
    Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Syamantak Majumder
    Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada
  • Bridgit B. Bowskill
    Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada
  • M. Golam Kabir
    Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada
  • Suzanne L. Advani
    Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada
  • Ian W. Gibson
    Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada
  • Manish M. Sood
    Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
  • Andrew Advani
    Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada
  • David Z. I. Cherney
    Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada

説明

<jats:p>Focal segmental glomerulosclerosis (FSGS) is an important cause of nondiabetic chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibition (SGLT2i) therapy attenuates the progression of diabetic nephropathy, but it remains unclear whether SGLT2i provides renoprotection in nondiabetic CKD such as FSGS. The primary aim of this pilot study was to determine the effect of 8 wk of dapagliflozin on glomerular filtration rate (GFR) in humans and in experimental FSGS. Secondary end points were related to changes in renal hemodynamic function, proteinuria, and blood pressure (BP). GFR (inulin) and renal plasma flow (para-aminohippurate), proteinuria, and BP were measured in patients with FSGS ( n = 10), and similar parameters were measured in subtotally nephrectomized (SNx) rats. In response to dapagliflozin, changes in GFR, renal plasma flow, and 24-h urine protein excretion were not statistically significant in humans or rats. Systolic BP (SBP) decreased in SNx rats (196 ± 26 vs. 165 ± 33 mmHg; P < 0.001), whereas changes were not statistically significant in humans (SBP 112.7 ± 8.5 to 112.8 ± 11.2 mmHg, diastolic BP 71.8 ± 6.5 to 69.6 ± 8.4 mmHg; P = not significant), although hematocrit increased (0.40 ± 0.05 to 0.42 ± 0.05%; P = 0.03). In archival kidney tissue from a separate patient cohort, renal parenchymal SGLT2 mRNA expression was decreased in individuals with FSGS compared with controls. Short-term treatment with the SGLT2i dapagliflozin did not modify renal hemodynamic function or attenuate proteinuria in humans or in experimental FSGS. This may be related to downregulation of renal SGLT2 expression. Studies examining the impact of SGLT2i on markers of kidney disease in patients with other causes of nondiabetic CKD are needed.</jats:p>

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