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Exercise and chronic kidney disease: potential mechanisms underlying the physiological benefits

Nature Reviews Nephrology volume 19, pages 244–256 (2023)Cite this article

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Abstract

Increasing evidence indicates that exercise has beneficial effects on chronic inflammation, cardiorespiratory function, muscle and bone strength and metabolic markers in adults with chronic kidney disease (CKD), kidney failure or kidney transplants. However, the mechanisms that underlie these benefits have received little attention, and the available clinical evidence is mainly from small, short-duration (<12 weeks) exercise intervention studies. The available data, mainly from patients with CKD or on dialysis, suggest that exercise-mediated shifts towards a less inflammatory immune cell profile, enhanced activity of the NRF2 pathway and reduced monocyte infiltration into adipose tissue may underlie improvements in inflammatory biomarkers. Exercise-mediated increases in nitric oxide release and bioavailability, reduced angiotensin II accumulation in the heart, left ventricular remodelling and reductions in myocardial fibrosis may contribute to improvements in left ventricular hypertrophy. Exercise stimulates an anabolic response in skeletal muscle in CKD, but increases in mitochondrial mass and satellite cell activation seem to be impaired in this population. Exercise-mediated activation of the canonical wnt pathway may lead to bone formation and improvements in the levels of the bone-derived hormones klotho and fibroblast growth factor 23 (FGF23). Longer duration studies with larger sample sizes are needed to confirm these mechanisms in CKD, kidney failure and kidney transplant populations and provide evidence for targeted exercise interventions.

Key points

  • Shifts towards a less inflammatory monocyte and T cell profile, enhanced activity of the NRF2 pathway and reduced monocyte infiltration into adipose tissue might underlie exercise-mediated improvements in inflammatory biomarkers in people with chronic kidney disease (CKD) or on dialysis.

  • Exercise-mediated enhancements in nitric oxide release and bioavailability, reduced angiotensin II accumulation in the heart, left ventricular remodelling and reductions in myocardial fibrosis might improve left ventricular hypertrophy in CKD and kidney failure.

  • Few studies have examined the effects of exercise training on insulin resistance in people with CKD; however, early evidence suggests that a 6-month exercise intervention might have beneficial effects.

  • Exercise, particularly resistance exercise, stimulates an anabolic response in skeletal muscle in people with CKD; exercise-induced increases in mitochondrial mass and satellite cell activation seem to be impaired in this population.

  • Exercise-mediated activation of the canonical wnt pathway may lead to bone formation in CKD; reduced fibroblast growth factor-23 (FGF23) release and increased klotho release in bone might also contribute to improved bone mineral density and reduced bone loss.

  • Studies with longer durations and larger sample sizes are needed to confirm these potential mechanisms in all CKD and kidney failure populations and provide evidence to enable the development of effective targeted exercise interventions.

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Fig. 1: Potential mechanisms that could underlie the anti-inflammatory effects of exercise in non-dialysis chronic kidney disease and haemodialysis populations.
Fig. 2: Key effects of exercise on skeletal muscle in CKD.
Fig. 3: Potential mechanisms that could underlie the physiological benefits of aerobic and resistance exercise in CKD.

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Acknowledgements

The authors’ work is supported by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. J.L.V’s work is supported by the Portuguese Foundation of Science and Technology (UID/04045/2020) and the Portuguese Society of Nephrology.

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Authors and Affiliations

  1. School of Sport, Exercise and Health Sciences and National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK

    Nicolette C. Bishop, James O. Burton & David J. Stensel

  2. National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and University of Leicester, Leicester, UK

    Nicolette C. Bishop, James O. Burton, Matthew P. M. Graham-Brown, David J. Stensel & Emma L. Watson

  3. Department of Cardiovascular Sciences, University of Leicester, Leicester, UK

    James O. Burton, Matthew P. M. Graham-Brown & Emma L. Watson

  4. John Walls Renal Unit, University Hospitals of Leicester NHS Trust, Leicester, UK

    James O. Burton & Matthew P. M. Graham-Brown

  5. Faculty of Sport Sciences, Waseda University, Tokorozawa, Japan

    David J. Stensel

  6. Department of Sports Science and Physical Education, The Chinese University of Hong Kong, Hong Kong, China

    David J. Stensel

  7. Research Centre in Sports Sciences, Health Sciences and Human Development, University of Maia, Maia, Portugal

    João L. Viana

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All authors researched data for the article, wrote the article and reviewed and/or edited the manuscript before submission. N.C.B. contributed substantially to discussion of the content.

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Glossary

Accelerometery

An objective measurement of movement (acceleration) that is used to quantify the volume and intensity of physical activity.

Blood flow restriction training

A technique that combines low-intensity exercise with blood flow occlusion through the application of a cuff or band with the aim of producing comparable effects with high-intensity exercise.

Dynamic resistance exercise

Effort against a constant force that involves movement of a joint through the range of motion, for example, lifting weights or press ups.

Isometric resistance exercise

Static contractions of a specific muscle or group of muscles with no resultant change in muscle length or joint movement.

Mechanotransduction

The conversion of mechanical loading into biochemical signalling.

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Bishop, N.C., Burton, J.O., Graham-Brown, M.P.M. et al. Exercise and chronic kidney disease: potential mechanisms underlying the physiological benefits. Nat Rev Nephrol 19, 244–256 (2023). https://doi.org/10.1038/s41581-022-00675-9

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