• 1.

    Johansen KL, Painter P. Exercise in individuals with CKD. Am J Kidney Dis 2012; 59:126134.

  • 2.

    MacKinnon HJ, et al. The association of physical function and physical activity with all-cause mortality and adverse clinical outcomes in nondialysis chronic kidney disease: A systematic review. Ther Adv Chronic Dis 2018; 9:209226.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Lopes AA, et al. Associations of self-reported physical activity types and levels with quality of life, depression symptoms, and mortality in hemodialysis patients: the DOPPS. Clin J Am Soc Nephrol 2014; 9:17021712.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Kutner NG, et al. Gait speed and mortality, hospitalization, and functional status change among hemodialysis patients: A US Renal Data System special study. Am J Kidney Dis 2015; 66:297304.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    London GM, Drueke TB. Atherosclerosis and arteriosclerosis in chronic renal failure. Kidney Int 1997; 51:16781695.

  • 6.

    Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med 1999; 340:115126.

  • 7.

    Zoungas S, et al. Association of carotid intima-medial thickness and indices of arterial stiffness with cardiovascular disease outcomes in CKD. Am J Kidney Dis 2007; 50:622630.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Van Craenenbroeck AH, Van Craenenbroeck EM, Kouidi E, et al. Vascular effects of exercise training in CKD: current evidence and pathophysiological mechanisms. Clin J Am Soc Nephrol 2014; 9:13051318.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Viana JL, et al. Evidence for anti-inflammatory effects of exercise in CKD. J Am Soc Nephrol 2014; 25:21212130.

  • 10.

    Beck DT, et al. Exercise training improves endothelial function in young prehypertensives. Exp Biol Med (Maywood) 2013; 238:433441.

  • 11.

    Hambrecht R, et al. Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation 2003; 107:31523158.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Hambrecht R, et al. Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure. Circulation 1998; 98:27092715.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Kirkman DL, et al. The effects of aerobic exercise on vascular function in non-dialysis chronic kidney disease: A randomized controlled trial. Am J Physiol Renal Physiol 2019.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Van Craenenbroeck AH, Van Craenenbroeck EM, Van Ackeren K, et al. Effect of moderate aerobic exercise training on endothelial function and arterial stiffness in CKD stages 3-4: A randomized controlled trial. Am J Kidney Dis 2015; 66:285296.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Koh KP, et al. Effect of intradialytic versus home-based aerobic exercise training on physical function and vascular parameters in hemodialysis patients: A randomized pilot study. Am J Kidney Dis 2010; 55:8899.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Greenwood SA, et al. Aerobic or resistance training and pulse wave velocity in kidney transplant recipients: A 12-week pilot randomized controlled trial (the exercise in renal transplant (ExeRT) Trial). Am J Kidney Dis 2015; 66:689698.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    O’Connor EM, et al. Long-term pulse wave velocity outcomes with aerobic and resistance training in kidney transplant recipients—A pilot randomised controlled trial. PLoS One 2017; 12:e0171063.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Dickinson HO, et al. Lifestyle interventions to reduce raised blood pressure: a systematic review of randomized controlled trials. J Hypertens 2006; 24:215233.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Thompson S, et al. The effect of exercise on blood pressure in chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials. PLoS One 2019; 14:e0211032.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Vanden Wyngaert K, Van Craenenbroeck AH, Van Biesen W, et al. The effects of aerobic exercise on eGFR, blood pressure and VO2peak in patients with chronic kidney disease stages 3-4: A systematic review and meta-analysis. PLoS One 2018; 13:e0203662.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Greenwood SA, Castle E, Lindup H, et al. Mortality and morbidity following exercise-based renal rehabilitation in patients with chronic kidney disease: the effect of programme completion and change in exercise capacity. Nephrol Dial Transplant 2019; 34:618625.

    • Crossref
    • Search Google Scholar
    • Export Citation

Can Exercise Training Affect Cardiovascular Morbidity in Patients with CKD?

  • 1 Amaryllis H. Van Craenenbroeck, MD, PhD, is with the Department of Microbiology, Immunology and Transplantation, KU, and the Department of Nephrology and Renal Transplantation, University Hospitals, Leuven, Belgium.
Full access

Decreased exercise capacity and cardiovascular risk are integral features of chronic kidney disease (CKD), with a debilitating impact on quality of life and survival.

Exercise capacity (VO2peak) is an objective assessment of physical functioning, which is the ability to perform physical activity. Physical activity (including exercise) is defined as any bodily movement produced by skeletal muscles resulting in energy expenditure (1). Both reduced physical functioning and physical activity are associated with an increased risk of adverse clinical outcomes in both non-dialysis–dependent (2) and dialysis-dependent people with CKD (3, 4).

Independent of this risk, individuals with CKD must cope with an extremely high cardiovascular risk. The pathophysiology and phenotype of vascular disease in CKD patients is unique: both the intimal and medial layer are concomitantly affected, in part by common mechanisms, resulting in different clinical entities (5): endothelial dysfunction (the harbinger of atherosclerosis) (6) and arterial stiffness (7), respectively.

Given the association of both exercise capacity and cardiovascular disease with mortality in CKD, several trials have been conducted to investigate causality and the effectiveness of physical activity interventions to improve outcomes. The outcomes studied in this context are manifold and vary from molecular mechanistic endpoints to survival.

Besides traditional risk factor modification, exercise improves vascular health through increased nitric oxide bioavailability and generalized anti-oxidative and anti-inflammatory effects both in patients with and without CKD (8, 9). For endothelial function in vivo, there is extensive clinical evidence that regular physical training partially corrects endothelial dysfunction in prehypertensive subjects (10) and in patients with coronary artery disease (11) and chronic heart failure (12). However, evidence in CKD from properly conducted randomized clinical trials (RCT) is scarce and conflicting.

In non-dialysis–dependent patients with CKD, a 12-week aerobic exercise training program improved microvascular function, possibly as a consequence of improved redox balance (13). Despite a greater increase in VO2- peak with a similar 12-week aerobic training regimen, another study did not show improvement in flow-mediated dilation, the gold standard of non-invasive endothelial function measurement (14). Neither study observed an effect on pulse wave velocity (PWV), a measurement of arterial stiffness. This finding is in line with findings in dialysis patients, where a 6-month aerobic exercise training program did not affect PWV (15).

In kidney transplant recipients, however, implementation of a regular aerobic or resistance training program for 3 months resulted in a significant improvement of PWV (16). This beneficial effect can be maintained for up to 12 months by self-managed physical activity (17). In line with findings in the general population (18), a recent meta-analysis confirmed the blood pressure–lowering effect of exercise training (combined aerobic and resistance) in hemodialysis patients using data from 1254 patients in 33 trials. The effect in non-dialysis–dependent CKD is less unequivocal, with a significant blood pressure–lowering effect after 24 weeks of aerobic training (19), but no overall effect at 52 weeks (20). Data regarding cardiovascular mortality is derived from only one (retrospective) study, which reported an association of improved cardiovascular outcome after completion of a 3-month rehabilitation program (21).

In conclusion, well-designed large RCTs in CKD with CV primary endpoints are scarce, but clinical evidence on the beneficial effects outweighs data on potential harm. Accordingly, patient counseling to emphasize the importance of regular physical activity has been incorporated in American and European clinical practice guidelines.

The stage has been set to test and formally establish from which type of exercise training, and at what intensity and dose, patients derive the largest benefit in well-designed RCTs with sufficient power.

References

  • 1.

    Johansen KL, Painter P. Exercise in individuals with CKD. Am J Kidney Dis 2012; 59:126134.

  • 2.

    MacKinnon HJ, et al. The association of physical function and physical activity with all-cause mortality and adverse clinical outcomes in nondialysis chronic kidney disease: A systematic review. Ther Adv Chronic Dis 2018; 9:209226.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Lopes AA, et al. Associations of self-reported physical activity types and levels with quality of life, depression symptoms, and mortality in hemodialysis patients: the DOPPS. Clin J Am Soc Nephrol 2014; 9:17021712.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Kutner NG, et al. Gait speed and mortality, hospitalization, and functional status change among hemodialysis patients: A US Renal Data System special study. Am J Kidney Dis 2015; 66:297304.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    London GM, Drueke TB. Atherosclerosis and arteriosclerosis in chronic renal failure. Kidney Int 1997; 51:16781695.

  • 6.

    Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med 1999; 340:115126.

  • 7.

    Zoungas S, et al. Association of carotid intima-medial thickness and indices of arterial stiffness with cardiovascular disease outcomes in CKD. Am J Kidney Dis 2007; 50:622630.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Van Craenenbroeck AH, Van Craenenbroeck EM, Kouidi E, et al. Vascular effects of exercise training in CKD: current evidence and pathophysiological mechanisms. Clin J Am Soc Nephrol 2014; 9:13051318.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Viana JL, et al. Evidence for anti-inflammatory effects of exercise in CKD. J Am Soc Nephrol 2014; 25:21212130.

  • 10.

    Beck DT, et al. Exercise training improves endothelial function in young prehypertensives. Exp Biol Med (Maywood) 2013; 238:433441.

  • 11.

    Hambrecht R, et al. Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation 2003; 107:31523158.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Hambrecht R, et al. Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure. Circulation 1998; 98:27092715.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Kirkman DL, et al. The effects of aerobic exercise on vascular function in non-dialysis chronic kidney disease: A randomized controlled trial. Am J Physiol Renal Physiol 2019.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Van Craenenbroeck AH, Van Craenenbroeck EM, Van Ackeren K, et al. Effect of moderate aerobic exercise training on endothelial function and arterial stiffness in CKD stages 3-4: A randomized controlled trial. Am J Kidney Dis 2015; 66:285296.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Koh KP, et al. Effect of intradialytic versus home-based aerobic exercise training on physical function and vascular parameters in hemodialysis patients: A randomized pilot study. Am J Kidney Dis 2010; 55:8899.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Greenwood SA, et al. Aerobic or resistance training and pulse wave velocity in kidney transplant recipients: A 12-week pilot randomized controlled trial (the exercise in renal transplant (ExeRT) Trial). Am J Kidney Dis 2015; 66:689698.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    O’Connor EM, et al. Long-term pulse wave velocity outcomes with aerobic and resistance training in kidney transplant recipients—A pilot randomised controlled trial. PLoS One 2017; 12:e0171063.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Dickinson HO, et al. Lifestyle interventions to reduce raised blood pressure: a systematic review of randomized controlled trials. J Hypertens 2006; 24:215233.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Thompson S, et al. The effect of exercise on blood pressure in chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials. PLoS One 2019; 14:e0211032.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Vanden Wyngaert K, Van Craenenbroeck AH, Van Biesen W, et al. The effects of aerobic exercise on eGFR, blood pressure and VO2peak in patients with chronic kidney disease stages 3-4: A systematic review and meta-analysis. PLoS One 2018; 13:e0203662.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Greenwood SA, Castle E, Lindup H, et al. Mortality and morbidity following exercise-based renal rehabilitation in patients with chronic kidney disease: the effect of programme completion and change in exercise capacity. Nephrol Dial Transplant 2019; 34:618625.

    • Crossref
    • Search Google Scholar
    • Export Citation
Save