DKD treatment has evolved from RAAS inhibitors alone to four therapeutic pillars (RAAS, SGLT2i, finerenone, GLP-1 RA), each targeting distinct pathophysiological mechanisms for comprehensive nephroprotection.
30 years, 4 pillarsDKD treatment evolved from one drug class to four complementary pillars, each discovered through landmark trials over three decades
What the researchers found
DKD treatment evolved over 30 years from RAAS inhibitors alone to four pillars (RAAS, SGLT2i, finerenone, GLP-1 RA), each targeting distinct mechanisms: hemodynamic, glucose-mediated, mineralocorticoid, and metabolic/inflammatory.
Why it matters
DKD affects hundreds of millions. Understanding the four-pillar framework ensures patients receive maximum kidney protection.
How the study worked
Historical review of DKD therapeutic evolution with evidence from landmark trials establishing each treatment pillar.
What this study cannot tell us
Optimal combination and sequencing of four pillars not established by trials. Cost of four-drug therapy is significant.
How to read the evidence
Historical review of landmark trials establishing each pillar. Evidence base is strong for individual pillars.
When this study was published
Published in 2025.
The bigger picture
The DKD treatment paradigm now mirrors cardiovascular disease — multiple complementary drug classes targeting different disease mechanisms for optimal outcomes.
Questions still open
- Should all DKD patients receive all four pillars?
- What is the optimal sequencing of the four therapies?
- Will a fifth pillar emerge?
Common questions
What are the four pillars of kidney disease treatment in diabetes?
Do I need all four drugs?
Read the original research
Therapeutic Advances in Diabetic Kidney Disease: 30 Years of Evidence and the Rise of the "Fantastic Four" in Nephrology.
Cardiorenal medicine, 16(1), 44-57
Citation
Husain-Syed, Faeq; Yuecel, Goekhan; Daschner, Clara; Jochims, Jan; Yazdani, Babak. (2026). Therapeutic Advances in Diabetic Kidney Disease: 30 Years of Evidence and the Rise of the "Fantastic Four" in Nephrology.. Cardiorenal medicine, 16(1), 44-57. https://doi.org/10.1159/000550423