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European Journal of Applied Physiology

, Volume 113, Issue 8, pp 2111–2124 | Cite as

Combined walking exercise and alkali therapy in patients with CKD4–5 regulates intramuscular free amino acid pools and ubiquitin E3 ligase expression

  • Emma L. Watson
  • George C. Kosmadakis
  • Alice C. Smith
  • Joao L. Viana
  • Jeremy R. Brown
  • Karen Molyneux
  • Izabella Z. A. Pawluczyk
  • Michael Mulheran
  • Nicolette C. Bishop
  • Susan Shirreffs
  • Ronald J. Maughan
  • Paul J. Owen
  • Stephen G. John
  • Christopher W. McIntyre
  • John Feehally
  • Alan BevingtonEmail author
Original Article
First Online:

Abstract

Muscle-wasting in chronic kidney disease (CKD) arises from several factors including sedentary behaviour and metabolic acidosis. Exercise is potentially beneficial but might worsen acidosis through exercise-induced lactic acidosis. We studied the chronic effects of exercise in CKD stage 4–5 patients (brisk walking, 30 min, 5 times/week), and non-exercising controls; each group receiving standard oral bicarbonate (STD), or additional bicarbonate (XS) (Total n = 26; Exercising + STD n = 9; Exercising +XS n = 6; Control + STD n = 8; Control + XS n = 3). Blood and vastus lateralis biopsies were drawn at baseline and 6 months. The rise in blood lactate in submaximal treadmill tests was suppressed in the Exercising + XS group. After 6 months, intramuscular free amino acids (including the branched chain amino acids) in the Exercising + STD group showed a striking chronic depletion. This did not occur in the Exercising + XS group. The effect in Exercising + XS patients was accompanied by reduced transcription of ubiquitin E3-ligase MuRF1 which activates proteolysis via the ubiquitin–proteasome pathway. Other anabolic indicators (Akt activation and suppression of the 14 kDa actin catabolic marker) were unaffected in Exercising + XS patients. Possibly because of this, overall suppression of myofibrillar proteolysis (3-methylhistidine output) was not observed. It is suggested that alkali effects in exercisers arose by countering exercise-induced acidosis. Whether further anabolic effects are attainable on combining alkali with enhanced exercise (e.g. resistance exercise) merits further investigation.

Keywords

Acidosis Aerobic exercise Amino acids Chronic kidney disease Skeletal muscle Ubiquitin–proteasome pathway 
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Notes

Acknowledgments

This work was partly supported by Kidney Research UK Grant RP33/1/2007. George Kosmadakis was supported by the Hellenic Society of Nephrology, and João Viana by the Portuguese Foundation for Science and Technology. Part of the patient characteristic data in Tables 1 and 3 has been published previously (Kosmadakis et al. 2011). Part of this data has been presented in abstract form previously; “Collapse of intramuscular free amino acid pools in patients with CKD4–5 after 6 months of walking exercise is prevented by alkali supplements”. Presented at the International congress on nutrition and metabolism in renal disease, Lausanne, 2010.

Conflict of interest

None to declare.

Supplementary material

421_2013_2628_MOESM1_ESM.doc (47 kb)
Supplementary material 1 (DOC 47 kb)
421_2013_2628_MOESM2_ESM.doc (113 kb)
Supplementary material 2 (DOC 113 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Emma L. Watson
    • 1
  • George C. Kosmadakis
    • 2
  • Alice C. Smith
    • 1
    • 2
  • Joao L. Viana
    • 3
    • 4
  • Jeremy R. Brown
    • 2
  • Karen Molyneux
    • 1
    • 2
  • Izabella Z. A. Pawluczyk
    • 1
  • Michael Mulheran
    • 5
  • Nicolette C. Bishop
    • 3
  • Susan Shirreffs
    • 3
  • Ronald J. Maughan
    • 3
  • Paul J. Owen
    • 6
  • Stephen G. John
    • 6
  • Christopher W. McIntyre
    • 6
  • John Feehally
    • 1
    • 2
  • Alan Bevington
    • 1
    Email author
  1. 1.Department of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences BuildingUniversity of LeicesterLeicesterUK
  2. 2.John Walls Renal UnitUniversity Hospitals of Leicester NHS TrustLeicesterUK
  3. 3.School of Sport, Exercise and Health SciencesLoughborough UniversityLoughboroughUK
  4. 4.Research Centre in Sports, Health Sciences and Human Development (CIDESD), Higher Education Institute of Maia (ISMAI)MaiaPortugal
  5. 5.Department of Medical and Social Care EducationUniversity of LeicesterLeicesterUK
  6. 6.School of Graduate Entry Medicine and HealthUniversity of NottinghamDerbyUK

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