title: Combined walking exercise and alkali therapy in patients with CKD4-5 regulates intramuscular free amino acid pools and ubiquitin E3 ligase expression.
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.
authors.affiliation: Department of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester, Leicester, LE1 9HN, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Watson
authors.forename: George C
authors.initials: GC
authors.lastname: Kosmadakis
authors.forename: Alice C
authors.initials: AC
authors.lastname: Smith
authors.forename: Joao L
authors.initials: JL
authors.lastname: Viana
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Brown
authors.forename: Karen
authors.initials: K
authors.lastname: Molyneux
authors.forename: Izabella Z A
authors.initials: IZ
authors.lastname: Pawluczyk
authors.forename: Michael
authors.initials: M
authors.lastname: Mulheran
authors.forename: Nicolette C
authors.initials: NC
authors.lastname: Bishop
authors.forename: Susan
authors.initials: S
authors.lastname: Shirreffs
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Maughan
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Owen
authors.forename: Stephen G
authors.initials: SG
authors.lastname: John
authors.forename: Christopher W
authors.initials: CW
authors.lastname: McIntyre
authors.forename: John
authors.initials: J
authors.lastname: Feehally
authors.forename: Alan
authors.initials: A
authors.lastname: Bevington
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000378:metabolism*; D001639:Bicarbonates / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000628:therapy*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D016138:Walking
chemical_list: D000596:Amino Acids; D001639:Bicarbonates; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; D019344:Lactic Acid; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases; D051057:Proto-Oncogene Proteins c-akt