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Updated: May 20, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
10:31

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

Published on: May 2, 2025

2012 update on diabetic kidney disease: the expanding spectrum, novel pathogenic insights and recent clinical trials

B Fernández Fernández1, U Elewa, M D Sánchez-Niño

  • 1Nephrology, IIS-Fundación Jiménez Díaz, Madrid, Spain.

Minerva Medica
|July 19, 2012
PubMed

Insights

Diabetic kidney disease (DKD) treatments targeting the renin-angiotensin-aldosterone system (RAAS) are insufficient. New therapeutic targets like TRAIL, CD74, and BASP1 show promise for managing DKD progression.

Area of Science:

  • Nephrology
  • Diabetology
  • Pharmacology

Background:

  • Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, with current renin-angiotensin-aldosterone system (RAAS) targeting therapies proving insufficient.
  • Podocyte injury and albuminuria are key DKD indicators, but 30% of diabetic patients show impaired kidney function without significant albuminuria, suggesting additional pathogenic factors.
  • The limitations of RAAS blockade, including disappointing clinical trial outcomes and safety concerns with dual blockade, necessitate exploration of alternative therapeutic strategies.

Purpose of the Study:

  • To review the current understanding of Diabetic Kidney Disease (DKD) pathogenesis and treatment limitations.
  • To highlight emerging therapeutic targets and diagnostic approaches beyond traditional RAAS blockade.
  • To discuss the potential of novel agents and biomarkers for improved DKD management.

Main Methods:

  • Review of current literature on DKD pathophysiology and treatment.
  • Analysis of clinical trial outcomes for various DKD interventions.
  • -Omics approaches (proteomics) and identification of novel biomarkers and therapeutic targets.

Main Results:

  • Current RAAS-targeting therapies are insufficient for preventing or reversing DKD, especially in cases lacking significant albuminuria.
  • Alternative therapeutic targets, including cytokine TRAIL, MIF receptor CD74, and protein BASP1, have been identified through -omics studies.
  • Urinary proteomics revealed a peptidomic fingerprint for DKD progression preceding microalbuminuria, with ongoing validation for early treatment.

Conclusions:

  • DKD management requires novel therapeutic strategies beyond RAAS blockade due to treatment limitations and evolving understanding of the disease spectrum.
  • Emerging targets and early diagnostic biomarkers, such as the urinary peptidomic fingerprint, offer potential for improved patient outcomes.
  • Further research and clinical trials are essential to validate new therapeutic agents like bardoxolone methyl and to re-evaluate others for advanced DKD treatment.

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