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Updated: Nov 18, 2025

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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Pathophysiology of diabetic kidney disease: impact of SGLT2 inhibitors

Ralph A DeFronzo1, W Brian Reeves2, Alaa S Awad2

  • 1Division of Diabetes, University of Texas Long School of Medicine, San Antonio, TX, USA. defronzo@uthscsa.edu.

Nature Reviews. Nephrology
|February 6, 2021
PubMed

Insights

Diabetic kidney disease (DKD) is a major cause of kidney failure. While hyperglycemia drives DKD, multiple factors contribute, necessitating combination therapies for effective treatment.

Area of Science:

  • Nephrology
  • Endocrinology
  • Diabetology

Background:

  • Diabetic kidney disease (DKD) is the leading cause of kidney failure globally, with prevalence increasing over 30 years.
  • Hyperglycemia is the primary driver of DKD, leading to numerous pathophysiological disturbances.
  • These include hypertension, renal hypoxia, inflammation, and podocyte injury, contributing to progressive kidney damage.

Purpose of the Study:

  • To review the multifactorial pathophysiology of diabetic kidney disease.
  • To discuss the role of hyperglycemia and associated disturbances in DKD progression.
  • To evaluate the potential of combination therapies for managing DKD.

Main Methods:

  • Literature review of studies on diabetic kidney disease pathophysiology.
  • Analysis of the impact of hyperglycemia and related factors on kidney function.
  • Examination of the therapeutic effects of Sodium-glucose co-transporter 2 (SGLT2) inhibitors.

Main Results:

  • Hyperglycemia initiates a cascade of pathophysiological events in DKD.
  • Multiple factors like hypertension, inflammation, and mitochondrial dysfunction exacerbate kidney damage.
  • Sodium-glucose co-transporter 2 (SGLT2) inhibitors show promise in addressing some of these abnormalities.

Conclusions:

  • Diabetic kidney disease progression is driven by complex, multifactorial pathophysiological processes.
  • Effective management likely requires combination therapies targeting multiple pathways.
  • Further research is needed to determine the optimal combination strategies for DKD.

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