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A Framework for Risk-Based Implementation of Combination Therapy in CKD: Who, Why, When, and How?

Emily K Yeung1, Janani Rangaswami2,3, Katherine R Tuttle4,5

  • 1The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.

Clinical Journal of the American Society of Nephrology : CJASN
|June 23, 2026
PubMed

Insights

New combination therapies, including SGLT2 inhibitors and MRAs, offer improved outcomes for chronic kidney disease (CKD) patients. A risk-based approach guides treatment intensity for better kidney and cardiovascular health.

Area of Science:

  • Nephrology
  • Cardiology
  • Pharmacology

Background:

  • Chronic kidney disease (CKD) management has evolved with new therapeutic classes.
  • Significant residual kidney and cardiovascular risk persists despite existing treatments.

Purpose of the Study:

  • To review the expanding therapeutic landscape for CKD.
  • To evaluate the role of combination therapy in reducing residual risk.
  • To outline a risk-based approach for guiding treatment decisions.

Main Methods:

  • Analysis of evidence from large randomized trials and meta-analyses.
  • Review of data on sodium-glucose co-transporter 2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (MRAs), and glucagon-like peptide-1 (GLP-1) receptor agonists.
  • Assessment of risk-based stratification using albuminuria and validated risk equations.

Main Results:

  • SGLT2 inhibitors, MRAs, and GLP-1 receptor agonists demonstrate independent and additive benefits in CKD.
  • Certain combinations show potential for improved safety profiles.
  • A risk-based approach aids in guiding treatment intensity and timely initiation of multidrug regimens.

Conclusions:

  • Combination therapy represents a significant advancement in managing CKD.
  • Risk stratification is crucial for optimizing treatment strategies.
  • Addressing implementation barriers and advancing combination therapies are key to improving long-term CKD outcomes.
Keywords:
ACE inhibitorsCKDGLP-1 receptor agonistsSGLT2 inhibitorsalbuminuriadiabetic kidney disease

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