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Title: Combined walking exercise and alkali therapy in patients with CKD4-5 regulates intramuscular free amino acid pools and ubiquitin E3 ligase expression.
Authors: Watson, Emma L.
Kosmadakis, George C.
Smith, Alice C.
Viana, Joao L.
Brown, Jeremy R.
Molyneux, Karen
Pawluczyk, Izabella Z.
Mulheran, Michael
Bishop, Nicolette C.
Shirreffs, Susan
Maughan, Ronald J.
Owen, Paul J.
John, Stephen G.
McIntyre, Christopher W.
Feehally, John
Bevington, Alan
First Published: 17-Apr-2013
Publisher: Springer Verlag
Citation: European Journal of Applied Physiology and Occupational Physiology, 2013, available online in advance of print
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.
DOI Link: 10.1007/s00421-013-2628-5
ISSN: 1439-6319
eISSN: 1439-6327
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © Springer-Verlag Berlin Heidelberg 2013. Deposited with reference to the publisher's archiving policy available on the SHERPA/RoMEO website. The final publication is available at
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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