University of Leicester
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Combined walking exercise and alkali therapy in patients with CKD4-5 regulates intramuscular free amino acid pools and ubiquitin E3 ligase expression.

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posted on 2013-04-23, 14:14 authored by Emma L. Watson, George C. Kosmadakis, Alice C. Smith, Joao L. Viana, Jeremy R. Brown, Karen Molyneux, Izabella Z. Pawluczyk, Michael Mulheran, Nicolette C. Bishop, Susan Shirreffs, Ronald J. Maughan, Paul J. Owen, Stephen G. John, Christopher W. McIntyre, John Feehally, Alan Bevington
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.



European Journal of Applied Physiology and Occupational Physiology, 2013, available online in advance of print

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation


  • AM (Accepted Manuscript)

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European Journal of Applied Physiology and Occupational Physiology


Springer Verlag





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