International Urology and Nephrology

, Volume 50, Issue 3, pp 527–534 | Cite as

Acute exercise during hemodialysis prevents the decrease in natural killer cells in patients with chronic kidney disease: a pilot study

  • Maria Isabel Fuhro
  • Gilson P. Dorneles
  • Francini P. Andrade
  • Pedro R. T. Romão
  • Alessandra Peres
  • Mariane B. Monteiro
Nephrology - Original Paper



To evaluate the acute response of natural killer (NK) cell subsets of chronic kidney disease patients submitted to intradialytic exercise in a randomized crossover study.


Nine patients were submitted to a single bout of 20-min intradialytic exercise and a control hemodialysis (HD) session with an interval of 7 days between them. Peripheral blood sample was collected at baseline, during HD and immediately after HD in each trial to evaluate the peripheral frequency of NK cells and their subsets (CD3-CD56bright and CD3-CD56dim), systemic cortisol concentrations, C-reactive protein (CRP), creatine kinase activity (CK), and urea and creatinine levels.


HD therapy induced a significant decrease in NK cells frequency (p = 0.039), NK CD3-CD56bright cells (p = 0.04), and CD3-CD56dim cells (p = 0.036). On the other hand, no significant alterations were observed in NK cells and NK subsets during and after intradialytic exercise trial (p > 0.05). Neither trial altered CRP levels or serum CK activity during and after HD therapy (p > 0.05). However, HD therapy increased cortisol concentrations after HD therapy (p = 0.034).


This study suggests the potential role of intradialytic exercise to prevent the decrease in peripheral frequency of NK cell subsets during HD therapy. Moreover, moderate intensity intradialytic exercise did not exacerbate the systemic inflammation or induce muscle damage during HD therapy.


Inflammation Hemodialysis Exercise NK cells Immune response 



This study was funded by Brazilian agencies Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (MCTI/2014), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS).

Compliance with ethical standards

Conflict of interest

The authors declared they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study protocol was approved by the Ethics Committee of the Methodist University Center IPA. This study was registered in Registro Brasileiro de Ensaios Clínicos (U1111-1172-9511).

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Romão JR (2004) Chronic kidney disease: definition, epidemiology and classification. Bras J Nephrol 26:1–3Google Scholar
  2. 2.
    Nitta K, Akiba T, Kawashima A, Kimata N, Miwa N, Nishida E, Uchida K, Honda K, Yumura W, Nihei H (2002) Characterization of th1/th2 profile in uremic patients. Nephron J 91(3):492–495CrossRefGoogle Scholar
  3. 3.
    Stinghen AE, Bucharles S, Riella MC, Pecoits-Filho R (2010) Immune mechanisms involved in cardiovascular complications of chronic kidney disease. Blood Purif 29:114–120CrossRefPubMedGoogle Scholar
  4. 4.
    Meijer RW, Litjens NH, de Wit EA, Langerak AW, Baan CC, Betjes MG (2014) Uremia-associated immunological aging is stably imprinted in the T-cell system and not reversed by kidney transplantation. Transpl Int 27:1272–1284CrossRefGoogle Scholar
  5. 5.
    Panichi V, Migliori M, De Pietro S, Taccola D, Bianchi AM, Norpoth M, Metelli MR, Giovannini L, Tetta C, Palla R (2001) C reactive protein in patients with chronic renal diseases. Ren Fail 23:551–562CrossRefPubMedGoogle Scholar
  6. 6.
    Stuveling EM, Hillege HL, Bakker SJL, Gans RO, De Jong PE, De Zeeuw D (2003) C-reactive protein is associated with renal function abnormalities in a non-diabetic population. Kidney Int 63:654–661CrossRefPubMedGoogle Scholar
  7. 7.
    Betjes MG (2013) Immune cell dysfunction and inflammation in end-stage renal disease. Nat Rev Nephrol 9:255–265CrossRefPubMedGoogle Scholar
  8. 8.
    Moretta L, Bottino C, Pende D, Vitale M, Mingari MC, Moretta A (2005) Human natural killer cells: molecular mechanisms controlling NK cell activation and tumor cell lysis. Immunol Lett 100:7–13CrossRefPubMedGoogle Scholar
  9. 9.
    Cooper MA, Fehniger TA, Caligiuri MA (2001) The biology of human natural killer-cell subsets. Trends Immunol 22:633–640CrossRefPubMedGoogle Scholar
  10. 10.
    Poli A, Michel T, Thérésine M, Andrès E, Hentges F, Zimmer J (2009) CD56 bright natural killer (NK) cells: an important NK cell subset. Immunology 126:458–465CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Xiang FF, Zhu JM, Cao XS, Shen B, Zou JZ, Liu ZH, Zhang H, Teng J, Liu H, Ding XQ (2015) Lymphocyte depletion and subset alteration correlate to renal function in chronic kidney disease patients. Ren Fail 5:1–8Google Scholar
  12. 12.
    Vacher-Coponat H, Brunet C, Lyonnet L, Bonnet E, Loundou A, Sampol J, Moal V, Dussol B, Brunet P, Berland Y, Dignat-George F, Paul P (2008) Natural killer cell alterations correlate with loss of renal function and dialysis duration in uraemic patients. Nephrol Dial Transpl 23:1406–1414CrossRefGoogle Scholar
  13. 13.
    Peraldi MN, Berrou J, Dulphy N, Seidowsky A, Haas P, Boissel N, Metivier F, Randoux C, Kossari N, Guérin A, Geffroy S, Delavaud G, Marin-Esteban V, Glotz D, Charron D, Toubert A (2009) Oxidative stress mediates a reduced expression of the activating receptor NKG2D in NK cells from end-stage renal disease patients. J Immunol 182:1696–1705CrossRefPubMedGoogle Scholar
  14. 14.
    Law BMP, Wilkinson R, Wang X, Kildey K, Lindner M, Rist MJ, Beagley K, Healy H, Kassianos AJ (2017) Interferon-γ production by tubulointerstitial human CD56 bright natural killer cells contributes to renal fibrosis and chronic kidney disease progression. Kidney Int 92:79–88CrossRefPubMedGoogle Scholar
  15. 15.
    Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA (2011) The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol 11:607–615CrossRefPubMedGoogle Scholar
  16. 16.
    Ploeger HE, Takken T, De Greef MH, Timmons BW (2009) The effects of acute and chronic exercise on inflammatory markers in children and adults with a chronic inflammatory disease: a systematic review. Exerc Immunol Rev 15:6–41PubMedGoogle Scholar
  17. 17.
    Avesani CM, Trolonge S, Deleaval P, Baria F, Mafra D, Faxén-Irving G, Chauveau P, Teta D, Kamimura MA, Cuppari L, Chan M, Heimbürger O, Fouque D (2012) Physical activity and energy expenditure in haemodialysis patients: an international survey. Nephrol Dial Transpl 27:2430–2434CrossRefGoogle Scholar
  18. 18.
    Torino C, Manfredini F, Bolignano D, Aucella F, Baggetta R, Barillà A, Battaglia Y, Bertoli S, Bonanno G, Castellino P, Ciurlino D, Cupisti A, D’Arrigo G, De Paola L, Fabrizi F, Fatuzzo P, Fuiano G, Lombardi L, Lucisano G, Messa P, Rapanà R, Rapisarda F, Rastelli S, Rocca-Rey L, Summaria C, Zuccalà A, Tripepi G, Catizone L, Zoccali C, Mallamaci F, EXCITE Working Group (2014) Physical performance and clinical outcomes in dialysis patients: a secondary analysis of the EXCITE trial. Kidney Blood Press Res 39:205–211CrossRefPubMedGoogle Scholar
  19. 19.
    Sheng K, Zhang P, Chen L, Cheng J, Wu C, Chen J (2014) Intradialytic exercise in hemodialysis patients: a systematic review and meta-analysis. Am J Nephrol 40:478–490CrossRefPubMedGoogle Scholar
  20. 20.
    Peres A, Perotto DL, Dorneles GP, Fuhro MI, Monteiro MB (2015) Effects of intradialytic exercise on systemic cytokine in patients with chronic kidney disease. Ren Fail 37:1430–1434CrossRefPubMedGoogle Scholar
  21. 21.
    Cheema BS, Abas H, Smith BC (2011) Effect of resistance training during hemodialysis on circulating cytokines: a randomized controlled trial. Eur J Appl Physiol 111:1437–1445CrossRefPubMedGoogle Scholar
  22. 22.
    Dungey M, Bishop NC, Young HM, Burton JO, Smith AC (2015) The impact of exercising during haemodialysis on blood pressure, markers of cardiac injury and systemic inflammation—preliminary results of a pilot study. Kidney Blood Press Res 40:593–604CrossRefPubMedGoogle Scholar
  23. 23.
    Borg G (1985) An introduction to Borg’s RPE scale. Movement Publications, IthacaGoogle Scholar
  24. 24.
    Timmons BW, Cieslak T (2008) Human natural killer cell subsets and acute exercise: a brief review. Exerc Immunol Rev 14:8–23PubMedGoogle Scholar
  25. 25.
    Griveas I, Visvardis G (2005) Comparative analysis of immunophenotypic abnormalities in cellular immunity of uremic patients undergoing either hemodialysis or continuous ambulatory peritoneal dialysis. Ren Fail 27:279–282CrossRefPubMedGoogle Scholar
  26. 26.
    Eleftheriadis T, Kartsios C, Yannki E, Kazila P, Antoniadi G, Liakopoulos V, Markala D (2008) Chronic inflammation and CD16+ natural killer cell zeta-chain downregulation in hemodialysis patients. Blood Purific 26:317–321CrossRefGoogle Scholar
  27. 27.
    Zaoui P, Hakim RM (1993) Natural killer-cell function in hemodialysis patients: effect of the dialysis membrane. Kidney Int 43:1298–1305CrossRefPubMedGoogle Scholar
  28. 28.
    Pedersen L, Idorn M, Olofsson GH, Lauenborg B, Nookaew I, Hansen RH, Johannesen HH, Becker JC, Pedersen KS, Dethlefsen C, Nielsen J, Gehl J, Pedersen BK, Thor Straten P, Hojman P (2016) Voluntary running suppresses tumor growth through epinephrine- and IL-6-dependent NK cell mobilization and redistribution. Cell Metab 23:554–562CrossRefPubMedGoogle Scholar
  29. 29.
    Campbell JP, Riddell NE, Burns VE, Turner M, van Zanten JJ, Drayson MT, Bosch JA (2009) Acute exercise mobilises CD8+ T lymphocytes exhibiting an effector-memory phenotype. Brain Behav Immun 23:767–775CrossRefPubMedGoogle Scholar
  30. 30.
    Timmons BW, Tarnopolsky MA, Snider DP, Bar-Or O (2006) Puberty effects on NK cell responses to exercise and carbohydrate intake in boys. Med Sci Sports Exerc 38:864–874CrossRefPubMedGoogle Scholar
  31. 31.
    Millard AL, Valli PV, Stussi G, Mueller NJ, Yung GP, Seebach JD (2013) Brief exercise increases peripheral blood NK cell counts without immediate functional changes, but impairs their responses to ex vivo stimulation. Front Immunol 4:125CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Zimmer P, Schenk A, Kieven M, Holthaus M, Lehmann J, Lovenich L, Bloch W (2017) Exercise induced alterations in NK-cell cytotoxicity—methodological issues and future perspectives. Exerc Immunol Rev 23:66–81PubMedGoogle Scholar
  33. 33.
    Bigley AB, Rezvani K, Chew C, Sekine T, Pistillo M, Crucian B, Bollard CM, Simpson RJ (2014) Acute exercise preferentially redeploys NK-cells with a highly-differentiated phenotype and augments cytotoxicity against lymphoma and multiple myeloma target cells. Brain Behav Immun 39:160–171CrossRefPubMedGoogle Scholar
  34. 34.
    Lau KK, Obeid J, Breithaupt P, Belostotsky V, Arora S, Nguyen T, Timmons BW (2015) Effects of acute exercise on markers of inflammation in pediatric chronic kidney disease: a pilot study. Pediatr Nephrol 30:615–621CrossRefPubMedGoogle Scholar
  35. 35.
    Russcher M, Chaves I, Lech K, Koch BC, Nagtegaal JE, Dorsman KF, Jong A, Kayser M, van Faassen HM, Kema IP, van der Horst GT, Gaillard CA (2015) An observational study on disturbed peripheral circadian rhythms in hemodialysis patients. Chronobiol Int 32:848–857CrossRefPubMedGoogle Scholar
  36. 36.
    Gracia-Iguacel C, González-Parra E, Egido J, Lindholm B, Mahillo I, Carrero JJ, Ortiz A (2014) Cortisol levels are associated with mortality risk in hemodialysis patients. Clin Nephrol 82:247–256CrossRefPubMedGoogle Scholar
  37. 37.
    Afsar B (2014) The relationship of serum cortisol levels with depression, cognitive function and sleep disorders in chronic kidney disease and hemodialysis patients. Psychiatr Q 85:479–486CrossRefPubMedGoogle Scholar
  38. 38.
    Gatti C, Cavallo R, Sartori ML, Del Ponte D, Masera R, Salvadori A, Carignola R, Angeli A (1987) Inhibition by cortisol of human natural killer (NK) cell activity. J Steroid Biochem 26:49–58CrossRefPubMedGoogle Scholar
  39. 39.
    Smith C, Myburgh KH (2006) Are the relationships between early activation of lymphocytes and cortisol or testosterone influenced by intensified cycling training in men? Appl Physiol Nutr Metab 31:226–234CrossRefPubMedGoogle Scholar
  40. 40.
    Okutsu M, Ishii K, Niu K, Nagatomi R (2014) Cortisol is not the primary mediator for augmented CXCR4 expression on natural killer cells after acute exercise. J Appl Physiol 117:199–204CrossRefPubMedGoogle Scholar
  41. 41.
    Krukowski K, Eddy J, Kosik KL, Konley T, Janusek LW, Mathews HL (2011) Glucocorticoid dysregulation of natural killer cell function through epigenetic modification. Brain Behav Immun 25:239–249CrossRefPubMedGoogle Scholar
  42. 42.
    Gatti G, Cavallo R, Sartori ML, del Ponte D, Masera R, Salvadori A, Carignola R, Angeli A (1987) Inhibition by cortisol of human natural killer (NK) cell activity. J Steroid Biochem 26:49–58CrossRefPubMedGoogle Scholar
  43. 43.
    Giraldo E, Garcia JJ, Hinchado MD (2009) Exercise intensity-dependent changes in the inflammatory response in sedentary women: role of neuroendocrine parameters in the neutrophil phagocytic process and the pro-/anti-inflammatory cytokine balance. Neuro Immunol Modul 16:237–244Google Scholar
  44. 44.
    Nagao F, Suzui M, Takeda K, Yagita H, Okumura K (2000) Mobilization of NK cells by exercise: down modulation of adhesion molecules on NK cells by catecholamines. Am J Physiol Regul Integr Comp Physiol 279:R1251–E1256CrossRefPubMedGoogle Scholar
  45. 45.
    Campos C, Pera A, Lopez-Fernandez I, Alonso C, Tarazona R, Solana R (2014) Proinflammatory status influences NK cells subsets in the elderly. Immunol Lett 162:298–302CrossRefPubMedGoogle Scholar
  46. 46.
    Esgalhado M, Stockler-Pinto MB, de França Cardoso LF, Costa C, Barboza JE, Mafra D (2015) Effect of acute intradialytic strength physical exercise on oxidative stress and inflammatory responses in hemodialysis patients. Kidney Res Clin Pract 34:35–40CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Cheema BS, Smith BC, Singh MA (2005) A rationale for intradialytic exercise training as standard clinical practice in ESRD. Am J Kidney Dis 45:912–926CrossRefPubMedGoogle Scholar
  48. 48.
    Bohm J, Monteiro MB, Andrade FP, Veronese F, Thomé FS (2017) Acute effects of intradialytic aerobic exercise on solute removal, blood gases and oxidative stress in patients with chronic kidney disease. J Bras Nefrol 27:0Google Scholar
  49. 49.
    Musavian AS, Soleimani A, Masoudi Alavi N, Baseri A, Savari F (2015) Comparing the effects of active and passive intradialytic pedaling exercises on dialysis efficacy, electrolytes, hemoglobin, hematocrit, blood pressure and health-related quality of life. Nurs Midwifery Stud 4:e25922CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Kirkman DL, Roberts LD, Kelm M, Wagner J, Jibani MM, Macdonald JH (2013) Interaction between intradialytic exercise and hemodialysis adequacy. Am J Nephrol 38:475–482CrossRefPubMedGoogle Scholar
  51. 51.
    Orcy R, Antunes MF, Schiller T, Seus T, Bohlke M (2014) Aerobic exercise increases phosphate removal during hemodialysis: a controlled trial. Hemodial Int 18:450–458CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2017

Authors and Affiliations

  1. 1.Research CenterMethodist University Center IPAPorto AlegreBrazil
  2. 2.Graduate Program in Health Sciences, Laboratory of Cellular and Molecular ImmunologyFederal University of Health Sciences of Porto Alegre (UFCSPA)Porto AlegreBrazil
  3. 3.Federal University of Rio Grande do SulPorto AlegreBrazil
  4. 4.Physical Therapy DepartmentFederal University of Health Sciences of Porto Alegre (UFCSPA)Porto AlegreBrazil

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