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.
Highlights
Patients with Chronic Kidney Disease (CKD) have poor physical functioning and low exercise capacity (Johansen. 2007; Painter. 2005) arising from inactivity (Tawney et al 2003), muscle-wasting and reduced muscle function (Diesel et al 1990), inflammation (Kaizu et al 2003) and anaemia (Painter and Moore. 1994)
We have recently reported a controlled study of 6-months home walking exercise in pre-dialysis CKD patients stage 4-5 (Kosmadakis et al 2011)
This study aimed to test the hypothesis that exercise plus additional alkali exerts beneficial effects on muscle amino acid and protein metabolism which are not obtained with exercise alone
Summary
Patients with Chronic Kidney Disease (CKD) have poor physical functioning and low exercise capacity (Johansen. 2007; Painter. 2005) arising from inactivity (Tawney et al 2003), muscle-wasting and reduced muscle function (Diesel et al 1990), inflammation (Kaizu et al 2003) and anaemia (Painter and Moore. 1994). Benefits for pre-dialysis patients are potentially significant in view of the large patient numbers and prospect of earlier intervention to prevent e.g. cardiovascular disease For such exercise to be practical and sustainable, it should be sufficiently straightforward to be performed at home without specialised training or equipment. We have recently reported a controlled study of 6-months home walking exercise in pre-dialysis CKD patients stage 4-5 (Kosmadakis et al 2011) This demonstrated improved exercise tolerance and quality of life, reduced frequency and severity of uraemic symptoms, protection from deteriorating cardiovascular reactivity, and improved blood pressure control (Kosmadakis et al 2011)
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