The Effects of Exercise and Sport in Solid Organ Transplant Recipients: A Review.

Solid organ transplantation is the criterion standard treatment for many with end-organ failure and can offer a new independence from the burden of disease. However solid organ transplant recipients (SOTRs) remain at high risk of cardiovascular (CV) disease, and poor quality of life and physical functioning. Increasing physical activity and exercise can improve the health of the general population; however, the effects on those with a transplant remain unclear. Intensive exercise and sporting activity has the potential to be beneficial, although there remain concerns particularly around the effects on immune function and the CV system. This review summarizes what is known about the effects of exercise on determinants of health in SOTRs and then collates the available literature investigating the consequences of intensive exercise and sport on the health of SOTR. There is a paucity of high-quality research, with most evidence being case studies or anecdotal; this is understandable given the relatively few numbers of SOTRs who are performing sport and exercise at a high level. However, if suitable evidence-based guidelines are to be formed and SOTRs are to be given reassurances that their activity levels are not detrimental to their transplanted organ and overall health, then more high-quality studies are required

Inflammatory factors and exercise in chronic kidney disease.

Patients with chronic kidney disease frequently present with chronic elevations in markers of inflammation, a condition that appears to be exacerbated by disease progression and onset of haemodialysis. Systemic inflammation is interlinked with malnutrition and muscle protein wasting and is implicated in a number of morbidities including cardiovascular disease: the most common cause of mortality in this population. Research in the general population and other chronic disease cohorts suggests that an increase in habitual activity levels over a prolonged period may help redress basal increases in systemic inflammation. Furthermore, those populations with the highest baseline levels of systemic inflammation appear to have the greatest improvements from training. On the whole, the activity levels of the chronic kidney disease population reflect a sedentary lifestyle, indicating the potential for increasing physical activity and observing health benefits. This review explores the current literature investigating exercise and inflammatory factors in the chronic kidney disease population and then attempts to explain the contradictory findings and suggests where future research is required

Regular exercise during haemodialysis promotes an anti-inflammatory leukocyte profile

Background: Cardiovascular disease is the most common cause of mortality in haemodialysis (HD) patients and is highly predicted by markers of chronic inflammation. Regular exercise may have beneficial anti-inflammatory effects, but this is unclear in HD patients. This study assessed the effect of regular intradialytic exercise on soluble inflammatory factors and inflammatory leucocyte phenotypes. Methods: Twenty-two HD patients from a centre where intradialytic cycling was offered thrice weekly and 16 HD patients receiving usual care volunteered. Exercising patients aimed to cycle for 30 min at rating of perceived exertion of ‘somewhat hard’. Baseline characteristics were compared with 16 healthy age-matched individuals. Physical function, soluble inflammatory markers and leucocyte phenotypes were assessed again after 6 months of regular exercise. Results: Patients were less active than their healthy counterparts and had significant elevations in measures of inflammation [interleukin-6 (IL-6), C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), intermediate and non-classical monocytes; all P < 0.001]. Six months of regular intradialytic exercise improved physical function (sit-to-stand 60). After 6 months, the proportion of intermediate monocytes in the exercising patients reduced compared with non-exercisers (7.58 ± 1.68% to 6.38 ± 1.81% versus 6.86 ± 1.45% to 7.88 ± 1.66%; P < 0.01). Numbers (but not proportion) of regulatory T cells decreased in the non-exercising patients only (P < 0.05). Training had no significant effect on circulating IL-6, CRP or TNF-α concentrations. Conclusions: These findings suggest that regular intradialytic exercise is associated with an anti-inflammatory effect at a circulating cellular level but not in circulating cytokines. This may be protective against the increased risk of cardiovascular disease and mortality that is associated with chronic inflammation and elevated numbers of intermediate monocytes

The influence of acute moderate-to-high intensity aerobic exercise on markers of immune function and microparticles in renal transplant recipients.

Renal transplant recipients (RTRs) and non-dialysis chronic kidney disease (ND-CKD) patients display elevated circulating microparticle (MP) counts, whilst RTRs display immunosuppression-induced infection susceptibility. The impact of aerobic exercise on circulating immune cells and microparticles is unknown in RTRs. Fifteen RTRs (age 52.8±14.5 years, estimated glomerular filtration rate [eGFR] 51.7±19.8 ml/min/1.73m2 [mean ± SD]), 16 ND-CKD patients (54. ± 6.3 years, eGFR 61.9±21.0 ml/min/1.73m2, acting as a uremic control group), and 16 HCs (52.2±16.2 years, eGFR 85.6±6.1 ml/min/1.73m2) completed 20 minutes of walking at 60-70% VO2 peak. Venous blood samples were taken pre, post, and 1h post-exercise. Leukocytes and MPs were assessed using flow cytometry. Exercise increased classical (p = 0.001) and non-classical (p = 0.002) monocyte subset proportions but decreased the intermediate subset (p < 0.001) in all groups. Exercise also decreased the percentage of platelet-derived MPs that expressed tissue factor (TF+) in all groups (p = 0.01), though no other exercise-dependent effects were observed. The exercise-induced reduction in intermediate monocyte percentage suggests an anti-inflammatory effect, though this requires further investigation. The reduction in the percentage of TF+ platelet-derived MPs suggests reduced pro-thrombotic potential, though further functional assays are required. Exercise did not cause aberrant immune cell activation, suggesting its safety from an immunological standpoint (ISRCTN38935454)

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

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