Watson, Emma L.Kosmadakis, George C.Smith, Alice C.Viana, Joao L.Brown, Jeremy R.Molyneux, KarenPawluczyk, Izabella Z. A.Mulheran, MichaelBishop, Nicolette C.Shirreffs, SusanMaughan, Ronald J.Owen, Paul J.John, Stephen G.McIntyre, Christopher W.Feehally, JohnBevington, Alan2021-04-282021-04-282013http://hdl.handle.net/10400.24/1770Muscle-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.engAdultAgedAged, 80 and overAmino AcidsBicarbonatesCombined Modality TherapyFemaleHumansLactic AcidMaleMiddle AgedMuscle ProteinsMuscle, SkeletalProto-Oncogene Proteins c-aktRenal Insufficiency, ChronicTripartite Motif ProteinsUbiquitin-Protein LigasesExercise TherapyWalkingjournal article10.1007/s00421-013-2628-5