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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

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Sodium-glucose cotransporter 2 inhibitors: extending the indication to non-diabetic kidney disease?

Claire C J Dekkers1, Ron T Gansevoort2

  • 1Departments of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|February 1, 2020
PubMed

Insights

Sodium-glucose cotransporter 2 (SGLT2) inhibitors like canagliflozin show significant renal and cardiovascular benefits in patients with diabetic nephropathy. These SGLT2 inhibitors may offer greater cardiovascular protection in patients with lower kidney function.

Area of Science:

  • Nephrology
  • Cardiology
  • Endocrinology

Background:

  • The CREDENCE trial evaluated the renal effects of sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin in diabetic patients with kidney disease.
  • Previous studies focused on glucose-lowering effects, but recent trials highlight broader cardio-renal benefits.

Purpose of the Study:

  • To review the CREDENCE trial results on canagliflozin's renal outcomes.
  • To analyze cardiovascular outcome trials of SGLT2 inhibitors, particularly in relation to kidney function.
  • To explore potential mechanisms of action and applicability in non-diabetic chronic kidney disease.

Main Methods:

  • Analysis of the CREDENCE trial data for renal endpoints.
  • Meta-analysis of cardiovascular outcome trials involving SGLT2 inhibitors.
  • Review of post hoc analyses on glucose-independent effects.
  • Discussion of proposed mechanisms of action.

Main Results:

  • Canagliflozin significantly reduced the risk of end-stage renal disease, creatinine doubling, or renal death by 34% compared to placebo.
  • Cardiovascular benefits of SGLT2 inhibitors may be more pronounced in patients with lower estimated glomerular filtration rate (eGFR).
  • The cardio- and renoprotective effects appear independent of glucose-lowering efficacy.

Conclusions:

  • SGLT2 inhibitors demonstrate significant cardio-renal protective effects in diabetic nephropathy.
  • These benefits may extend to patients with non-diabetic chronic kidney diseases, warranting further investigation.
  • The glucose-independent mechanisms underlying these effects are a key area for future research.
Keywords:
CKDGFRcardiovascularclinical trialdiabetes mellitus

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