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Salt and chronic kidney disease

Nature Reviews Nephrology (2026) Cite this article

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An Author Correction to this article was published on 06 May 2026

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Abstract

Disruption of sodium homeostasis has a central role in the development and progression of chronic kidney disease (CKD). Excess dietary sodium can overwhelm regulatory mechanisms and amplify pathways that promote kidney injury, hypertension and cardiovascular disease. In CKD, altered sodium handling has haemodynamic effects, leads to activation of the renin–angiotensin–aldosterone system and contributes to tissue sodium accumulation, endothelial dysfunction and inflammatory responses that further accelerate disease progression. Emerging evidence suggests that variability in these pathways — shaped by genetic predisposition and heterogeneous CKD phenotypes — may influence individual susceptibility to sodium-mediated damage and responses to therapeutic interventions. Although dietary sodium restriction remains a cornerstone of CKD management, improved understanding of sodium homeostasis as a multidimensional driver of CKD provides a broader framework for understanding disease mechanisms and may help to refine risk stratification and treatment strategies to enable maximal clinical benefit for patients at a high risk of sodium-mediated complications.

Key points

  • A high-salt diet contributes to haemodynamic overload, reduced renal autoregulatory function and, eventually, hypertension and glomerular hyperfiltration.

  • High dietary salt intake and impaired sodium homeostasis result in sodium overload and tissue sodium accumulation, which interferes with endothelial function and contributes to systemic and renal inflammation.

  • Genetic background influences individual susceptibility to progressive renal impairment as a consequence of high dietary salt intake.

  • Chronic kidney disease-associated renal autoregulatory dysfunction, renin–angiotensin–aldosterone system dysregulation, endothelial dysfunction and systemic inflammation contribute to sensitivity of blood pressure to changes in dietary salt intake.

  • Pharmacological interventions for renoprotection, including renin–angiotensin–aldosterone system inhibitors, sodium–glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists, contribute to restoration of sodium homeostasis, thus alleviating the negative impact of excessive dietary salt on blood pressure and proteinuria.

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Fig. 1: The mosaic model applied to salt and chronic kidney disease.
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Fig. 2: A simplified framework of renin–angiotensin–aldosterone system dysregulation in chronic kidney disease.
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Fig. 3: Factors that contribute to salt sensitivity of blood pressure in chronic kidney disease.
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Fig. 4: Immune cells as sodium sensors and sodium as a driver of systemic and renal inflammation.
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Acknowledgements

The authors’ work was supported and made possible by funding from the Dutch Kidney Foundation (Senior Kolff grant number 18OKG12 to L.V.). The authors would like to thank Allan Detsky for his contributions to the clarity and structure of the manuscript.

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Authors and Affiliations

  1. Amsterdam UMC location University of Amsterdam, Department of Internal Medicine, Section of Nephrology, Meibergdreef 9, Amsterdam, The Netherlands

    Jacob Murray, Roos F. Marsman, Rik H. Olde Engberink & Liffert Vogt

  2. Amsterdam Cardiovascular Sciences, Diabetes and Hypertensive Diseases, Amsterdam UMC location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands

    Jacob Murray, Roos F. Marsman, Rik H. Olde Engberink & Liffert Vogt

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J.M. researched the data and wrote the article. All authors contributed substantially to discussion of the content and reviewed and/or edited the manuscript before submission.

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Correspondence to Liffert Vogt.

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Nature Reviews Nephrology thanks Matthew Bailey, who co-reviewed with Jessica Ivy; Christian Delles; and Jens Titze for their contribution to the peer review of this work.

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Glossary

Endothelial dysfunction

Impaired endothelial cell activity characterized by vasomotor dysregulation and reduced barrier function.

Relative hyperfiltration

An increase in single nephron glomerular filtration in response to a reduced number of nephrons. This response maintains total glomerular filtration rate.

Salt sensitivity of blood pressure

(SSBP). The magnitude of the rise in blood pressure that occurs following a salt load.

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Murray, J., Marsman, R.F., Engberink, R.H.O. et al. Salt and chronic kidney disease. Nat Rev Nephrol (2026). https://doi.org/10.1038/s41581-026-01076-y

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