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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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.
KeywordsAcidosis Aerobic exercise Amino acids Chronic kidney disease Skeletal muscle Ubiquitin–proteasome pathway
This work was partly supported by Kidney Research UK Grant RP33/1/2007. George Kosmadakis was supported by the Hellenic Society of Nephrology, and João Viana by the Portuguese Foundation for Science and Technology. Part of the patient characteristic data in Tables 1 and 3 has been published previously (Kosmadakis et al. 2011). Part of this data has been presented in abstract form previously; “Collapse of intramuscular free amino acid pools in patients with CKD4–5 after 6 months of walking exercise is prevented by alkali supplements”. Presented at the International congress on nutrition and metabolism in renal disease, Lausanne, 2010.
Conflict of interest
None to declare.
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