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[AUTOPHAGY AND DIABETIC NEPHROPATHY].

Evgeny Farber1, Anaam Hanut1, Hagar Tadmor2

  • 1Nephrology and Hypertension Division, The Medical Center in Galilee, Nahariya.

Harefuah
|November 24, 2021
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Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) show promise in managing diabetic nephropathy by reducing albuminuria and preserving kidney function. These drugs may positively influence autophagy, a cellular process crucial for kidney health in diabetes.

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Area of Science:

  • Nephrology
  • Endocrinology
  • Molecular Biology

Background:

  • Diabetes mellitus (DM) is a primary cause of end-stage renal disease, with 40% of patients needing renal replacement therapy within 20 years.
  • Diabetic nephropathy involves hyperfiltration, albuminuria, and is linked to inflammation, oxidative stress, and genetic factors like Haptoglobin 2-2.
  • Autophagy dysfunction under hyperglycemia contributes to diabetic nephropathy, while it's protective under normal glucose levels.

Purpose of the Study:

  • To investigate the role of autophagy in diabetic nephropathy pathogenesis.
  • To evaluate the impact of sodium-glucose cotransporter-2 inhibitors (SGLT2Is) on renal function and albuminuria in diabetic patients.
  • To explore the molecular mechanisms of SGLT2Is, particularly their effect on autophagy in renal cells.

Main Methods:

  • Review of preclinical and clinical studies on SGLT2I treatment in diabetic nephropathy.
  • Analysis of the role of autophagy in renal epithelial cells (podocytes, proximal tubules, mesangial, endothelial cells) under diabetic conditions.
  • Examination of molecular changes induced by SGLT2 inhibition in podocytes and proximal tubule cells.

Main Results:

  • SGLT2Is consistently reduce albuminuria and help maintain renal function in diabetic patients.
  • SGLT2 inhibition normalizes glomerular hyperfiltration characteristic of early diabetic nephropathy.
  • Evidence suggests SGLT2Is positively modulate basal autophagy in podocyte and proximal tubule cells.

Conclusions:

  • SGLT2 inhibitors represent a promising therapeutic strategy for diabetic nephropathy, improving renal outcomes.
  • Modulation of autophagy by SGLT2Is may be a key mechanism underlying their renoprotective effects.
  • Further research into the interplay between SGLT2 inhibition, autophagy, and diabetic kidney disease is warranted.