Evidence for anti-inflammatory effects of exercise in CKD.

CKD is associated with a complex state of immune dysfunction characterized by immune depression, predisposing patients to infections, and immune activation, resulting in inflammation that associates with higher risk of cardiovascular disease. Physical exercise may enhance immune function and exert anti-inflammatory effects, but such effects are unclear in CKD. We investigated the separate effects of acute and regular moderate-intensity aerobic exercise on neutrophil degranulation (elastase release), activation of T lymphocytes (CD69 expression) and monocytes (CD86 and HLA-DR expression), and plasma inflammatory markers (IL-6, IL-10, soluble TNF-receptors, and C-reactive protein) in patients with predialysis CKD. A single 30-minute (acute) bout of walking induced a normal pattern of leukocyte mobilization and had no effect on T-lymphocyte and monocyte activation but improved neutrophil responsiveness to a bacterial challenge in the postexercise period. Furthermore, acute exercise induced a systemic anti-inflammatory environment, evidenced by a marked increase in plasma IL-10 levels (peaked at 1 hour postexercise), that was most likely mediated by increased plasma IL-6 levels (peaked immediately postexercise). Six months of regular walking exercise (30 min/d for 5 times/wk) exerted anti-inflammatory effects (reduction in the ratio of plasma IL-6 to IL-10 levels) and a downregulation of T-lymphocyte and monocyte activation, but it had no effect on circulating immune cell numbers or neutrophil degranulation responses. Renal function, proteinuria, and BP were also unaffected. These findings provide compelling evidence that walking exercise is safe with regard to immune and inflammatory responses and has the potential to be an effective anti-inflammatory therapy in predialysis CKD.

Combined walking exercise and alkali therapy in patients with CKD4-5 regulates intramuscular free amino acid pools and ubiquitin E3 ligase expression.

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.

Benefits of regular walking exercise in advanced pre-dialysis chronic kidney disease.

BACKGROUND: There is increasing evidence of the benefit of regular physical exercise in a number of long-term conditions including chronic kidney disease (CKD). In CKD, this evidence has mostly come from studies in end stage patients receiving regular dialysis. There is little evidence in pre-dialysis patients with CKD Stages 4 and 5. METHODS: A prospective study compared the benefits of 6 months regular walking in 40 pre-dialysis patients with CKD Stages 4 and 5. Twenty of them were the exercising group and were compared to 20 patients who were continuing with usual physical activity. In addition, the 40 patients were randomized to receive additional oral sodium bicarbonate (target venous bicarbonate 29 mmol/L) or continue with previous sodium bicarbonate treatment (target 24 mmol/L). RESULTS: Improvements noted after 1 month were sustained to 6 months in the 18 of 20 who completed the exercise study. These included improvements in exercise tolerance (reduced exertion to achieve the same activity), weight loss, improved cardiovascular reactivity, avoiding an increase in blood pressure medication and improvements in quality of health and life and uraemic symptom scores assessed by questionnaire. Sodium bicarbonate supplementation did not produce any significant alterations. CONCLUSIONS: This study provides further support for the broad benefits of aerobic physical exercise in CKD. More studies are needed to understand the mechanisms of these benefits, to study whether resistance exercise will add to the benefit and to evaluate strategies to promote sustained lifestyle changes, that could ensure continued increase in habitual daily physical activity levels.