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  • Review Article
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Risk-directed management of chronic kidney disease

Nature Reviews Nephrology volume 21, pages 287–298 (2025)Cite this article

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Abstract

The timely and rational institution of therapy is a key step towards reducing the global burden of chronic kidney disease (CKD). CKD is a heterogeneous entity with varied aetiologies and diverse trajectories, which include risk of kidney failure but also cardiovascular events and death. Developments in the past decade include substantial progress in CKD risk prediction, driven in part by the accumulation of electronic health records data. In addition, large randomized clinical trials have demonstrated the effectiveness of sodium–glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antagonists in reducing adverse events in CKD, greatly expanding the options for effective therapy. Alongside angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, these classes of medication have been proposed to be the four pillars of CKD pharmacotherapy. However, all of these drug classes are underutilized, even in individuals at high risk. Leveraging prognostic estimates to guide therapy could help clinicians to prescribe CKD-related therapies to those who are most likely to benefit from their use. Risk-based CKD management thus aligns patient risk and care, allowing the prioritization of absolute benefit in determining therapeutic selection and timing. Here, we discuss CKD prognosis tools, evidence-based management and prognosis-guided therapies.

Key points

  • Widely validated risk tools can quantify the individual absolute risk of chronic kidney disease (CKD) progression, kidney failure, cardiovascular disease and death.

  • Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), sodium–glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 receptor agonists (GLP1RAs) and mineralocorticoid receptor antagonists (MRAs) are highly effective and safe medicines that reduce CKD progression, cardiovascular events and mortality. Although underutilized, these medications are increasingly recognized as the pillars supporting CKD therapy.

  • Combination therapy offers kidney, cardiovascular and overall survival benefits, along with safety advantages.

  • Risk-based CKD care aligns treatment intensity to patient risk and considers medication selection and timing. The largest absolute benefit is expected in patients with the highest risk of adverse outcomes.

  • For people at the highest risk, clinicians should consider initiation of SGLT2 inhibitors, GLP1RAs, ACE inhibitors or ARBs, and MRAs in an accelerated fashion to achieve the largest absolute risk reductions.

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Fig. 1: Application of CKD risk prognosis tools across disease categories and incidence of adverse events.
Fig. 2: Distribution of predicted 2-year risk of kidney failure determined by KFRE across CKD categories.
Fig. 3: Distribution of baseline predicted risk in the CANVAS and CREDENCE clinical trials.
Fig. 4: Distinct and overlapping clinical benefits from CKD pharmacotherapies.
Fig. 5: Stratified absolute change in chronic eGFR slope with canagliflozin initiation in the CANVAS programme.

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Acknowledgements

The authors thank K. Pandit, C. Flaherty and Y. Sang for their assistance in the design of figures for this manuscript before submission.

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  1. University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Matthew F. Blum

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

    Brendon L. Neuen

  3. New York University Grossman School of Medicine, New York, NY, USA

    Morgan E. Grams

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Blum, M.F., Neuen, B.L. & Grams, M.E. Risk-directed management of chronic kidney disease. Nat Rev Nephrol 21, 287–298 (2025). https://doi.org/10.1038/s41581-025-00931-8

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