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  • Review Article
  • Published:

Kidney–brain crosstalk in the acute and chronic setting

Nature Reviews Nephrology volume 11, pages 707–719 (2015)Cite this article

Subjects

Key Points

  • The majority of patients with chronic kidney disease (CKD) incur neurological complications that might improve following renal transplantation

  • Proteinuria, decreased glomerular filtration rate (GFR), and increased cystatin C are risk factors for cerebrovascular disease, which is in turn a risk factor for ongoing kidney dysfunction

  • Stroke is a major complication of CKD in elderly patients undergoing dialysis; conventional ischaemic risk factors, as well as dialysis itself, can contribute to the development of stroke

  • Patients undergoing dialysis often develop delirium after dialysis sessions, as well as chronic dementia, with prominent deficits in executive function and memory that are independent of age

  • Systemic inflammation, oxidative stress, and dysregulation of sodium, potassium, and water channels in acute kidney injury can lead to brain injury, dysfunction, and oedema

Abstract

Patients with kidney disease often exhibit multiple organ dysfunction that is caused, in part, by marked connectivity between the kidney and other organs and tissues. Substantial crosstalk occurs between the kidney and the brain, as indicated by the frequent presentation of neurological disorders, such as cerebrovascular disease, cognitive impairment, and neuropathy during the natural history of chronic kidney disease. The underlying pathophysiology of such comorbid neurological disorders in kidney disease is governed by shared anatomic and vasoregulatory systems and humoral and non-humoral bidirectional pathways that affect both the kidney and the brain. During acute kidney injury, the brain and kidney might interact through the amplification of cytokine-induced damage, extravasation of leukocytes, oxidative stress, and dysregulation of sodium, potassium, and water channels. The advent of dialysis and renal transplantation programmes has led to a reduction in the rate of neurological complications associated with uraemia, but a new set of complications have arisen as a consequence of the effects of dialysis on the central nervous system over the short and long term. This Review discusses the clinical complications of acute and chronic renal failure from a neurologic perspective, and highlights current understanding of the underlying pathophysiologies.

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Figure 1: MRI showing subclinical brain lesions in patients with chronic kidney disease.
Figure 2: Mechanisms of kidney–brain crosstalk during chronic and acute kidney disease.
Figure 3: Inflammatory processes that contribute to acute kidney injury (AKI) and other co-morbidities.
Figure 4: Innate immune signalling pathways in acute kidney injury (AKI) leading to brain inflammation.

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Acknowledgements

The authors would like to acknowledge that this Review was initiated during the international fellowship of R.L. at the Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, Vicenza, Italy.

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Authors and Affiliations

  1. Department of Nephrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Pu Jian Road 160, Shanghai, 200127, China

    Renhua Lu

  2. Brain & Mind Research Institute, Sydney Medical School, University of Sydney, 100 Mallett Street, Camperdown, 2050, NSW, Australia

    Matthew C. Kiernan

  3. Department of Medicine, Geriatrics Division, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, 55415, MN, USA

    Anne Murray

  4. Division of Nephrology, University of Virginia Health System, 1215 Lee Street, Charlottesville, 22908, VA, USA

    Mitchell H. Rosner

  5. Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, International Renal Research Institute of Vicenza, Viale Rodolfi 37, Vicenza, 36100, Italy

    Claudio Ronco

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  1. Renhua Lu
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  2. Matthew C. Kiernan
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Contributions

C.R. and R.L. researched the data for this article. R.L. and M.H.R. provided substantial contribution to the discussion of content. C.R., R.L., M.C.K. and A.M. contributed to the writing. All authors reviewed and/or edited the manuscript before submission.

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Correspondence to Claudio Ronco.

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Lu, R., Kiernan, M., Murray, A. et al. Kidney–brain crosstalk in the acute and chronic setting. Nat Rev Nephrol 11, 707–719 (2015). https://doi.org/10.1038/nrneph.2015.131

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