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Is There a Role for SGLT2 Inhibitors in Patients with End-Stage Kidney Disease?

Rehma Siddiqui1, Yoshitsugu Obi2, Neville R Dossabhoy1

  • 1Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, USA.

Current Hypertension Reports
|June 24, 2024
PubMed

Insights

Sodium-glucose transporter 2 (SGLT2) inhibitors show promise for dialysis patients at high cardiovascular risk. These drugs may offer direct cardiac benefits by reducing inflammation and oxidative stress, addressing an unmet need in end-stage kidney disease (ESKD) treatment.

Area of Science:

  • Nephrology
  • Cardiology
  • Pharmacology

Background:

  • End-stage kidney disease (ESKD) significantly increases cardiovascular disease (CVD) risk, the primary cause of death in dialysis patients.
  • Existing therapies inadequately manage this elevated CVD risk, indicating a need for novel treatments.
  • Sodium-glucose transporter 2 (SGLT2) inhibitors have shown cardiovascular and renal benefits in other populations but lack data in ESKD.

Purpose of the Study:

  • To review the potential cardiovascular benefits of SGLT2 inhibitors in patients with ESKD.
  • To explore the direct cardiac effects of SGLT2 inhibitors in the context of dialysis.
  • To examine current evidence and ongoing research regarding SGLT2 inhibitors for dialysis patients.

Main Methods:

  • Review of recent clinical and preclinical studies on SGLT2 inhibitors in dialysis patients.
  • Analysis of proposed mechanisms for direct cardiac benefits, including effects on intracellular ion levels, inflammation, autophagy, oxidative stress, and endoplasmic reticulum stress.
  • Examination of current clinical evidence, experimental data, safety concerns, and ongoing trials.

Main Results:

  • Preclinical and clinical data suggest SGLT2 inhibitors may benefit dialysis patients' cardiovascular health.
  • Potential benefits include indirect effects (preserving kidney function, improving anemia) and direct cardiac effects (reducing inflammation, oxidative stress, ER stress).
  • Ongoing trials are investigating the safety and efficacy of SGLT2 inhibitors in the dialysis population.

Conclusions:

  • SGLT2 inhibitors present a potential therapeutic strategy for improving cardiovascular outcomes in dialysis patients.
  • Further research, including dedicated clinical trials, is essential to confirm the safety and effectiveness of SGLT2 inhibitors in ESKD.
  • Addressing the high cardiovascular mortality in dialysis patients remains a critical unmet need that SGLT2 inhibitors may help fulfill.
Abstract

Keywords:
AutophagyChronic kidney diseaseDialysisEnd-stage kidney diseaseHeart failureInflammationMortalityOxydative stressResidual kidney functionSodium-glucose cotransporter-2 inhibitors

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