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Role of apoptosis in the pathogenesis of acute renal failure

Ramon Bonegio1, Wilfred Lieberthal

  • 1Renal Section, Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.

Current Opinion in Nephrology and Hypertension
|May 1, 2002
PubMed

Insights

Acute tubular necrosis involves both apoptosis and necrosis. Growth factors aid recovery by reducing apoptosis, while rapamycin hinders it, delaying renal function recovery.

Area of Science:

  • Nephrology
  • Cell Biology
  • Pathology

Background:

  • Renal tubular cells undergo apoptosis and necrosis in acute kidney injury (AKI).
  • The precise contribution of apoptosis to tubular cell loss in AKI remains unclear.
  • Growth factors show therapeutic benefits in AKI, likely via anti-apoptotic and proliferative effects.

Purpose of the Study:

  • To investigate the role of apoptosis in acute tubular necrosis.
  • To evaluate the impact of rapamycin on renal tubular cell apoptosis and regeneration.
  • To explore the therapeutic potential of targeting the apoptotic pathway in AKI.

Main Methods:

  • Utilized experimental models of ischemic and toxic acute renal failure.
  • Administered growth factors and rapamycin to assess their effects on renal function and cell death.
  • Examined the effects of caspase inhibitors on ischemia-reperfusion injury.

Main Results:

  • Rapamycin inhibits growth factor-induced proliferation and survival, increasing tubular cell apoptosis and delaying renal recovery.
  • Caspase inhibitors show protective effects in ischemia-reperfusion injury, but the mechanisms (reduced inflammation vs. reduced apoptosis) are uncertain.
  • The apoptotic pathway presents multiple targets for therapeutic intervention in AKI.

Conclusions:

  • Apoptosis significantly contributes to renal tubular cell loss in AKI.
  • Targeting apoptotic pathways, beyond caspase inhibition, offers promising therapeutic strategies for AKI.
  • Understanding the balance between apoptosis and regeneration is crucial for AKI treatment.

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