%0 Journal Article %A Watson, Emma L. %A Kosmadakis, George C. %A Smith, Alice C. %A Viana, Joao L. %A Brown, Jeremy R. %A Molyneux, Karen %A Pawluczyk, Izabella Z. %A Mulheran, Michael %A Bishop, Nicolette C. %A Shirreffs, Susan %A Maughan, Ronald J. %A Owen, Paul J. %A John, Stephen G. %A McIntyre, Christopher W. %A Feehally, John %A Bevington, Alan %D 2013 %T Combined walking exercise and alkali therapy in patients with CKD4-5 regulates intramuscular free amino acid pools and ubiquitin E3 ligase expression. %U https://figshare.le.ac.uk/articles/journal_contribution/Combined_walking_exercise_and_alkali_therapy_in_patients_with_CKD4-5_regulates_intramuscular_free_amino_acid_pools_and_ubiquitin_E3_ligase_expression_/10165784 %2 https://figshare.le.ac.uk/ndownloader/files/18320789 %K Acidosis %K aerobic exercise %K amino acids %K chronic kidney disease %K skeletal muscle %K ubiquitin-proteasome pathway %X 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. %I University of Leicester