Inflammatory Response to Exercise Training in Chronic Kidney Disease

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Excessive inflammation associated with chronic kidney disease (CKD) is believed to contribute to a variety of CKD co-morbidities, including renal osteodystrophy and cardiovascular disease. Endurance exercise training has anti-inflammatory effects in healthy populations, but little is known about the effects of exercise on inflammation in the setting of CKD. Here we present data examining the effects of 4 months of endurance exercise training on inflammation and associated disease risk factors in a mouse model of CKD and in renal disease patients receiving hemodialysis treatment. METHODS. Animal study: Uremia was surgically induced in ApoE-/- mice by 5/6th nephrectomy, then mice were randomly assigned to a sedentary (SED) or exercise training (EX) group for 4 months; EX mice ran on a treadmill 5 days/week for 45 minutes at ∼ 15 meters/min for 4 months. At sacrifice, circulating pro- and anti-inflammatory cytokine levels, aortic atherosclerosis and vascular calcification, and bone density (femur) was measured. Human study: 16 hemodialysis patients were randomly assigned to a SED or EX group for 4 months; those in the EX group cycled 3 days per week during their dialysis session for 45 minutes at a moderate intensity. Blood samples collected at baseline and after the intervention were used to measure circulating inflammatory variables (C-reactive protein; CRP), and markers of oxidative stress (TBARS, lipid peroxidation, and paraoxonase activity). In addition, ultrasound was used to measure arterial and cardiac structure and function. RESULTS: Exercise training had little effect on circulating inflammatory markers, aortic atherosclerosis, or vascular calcification in uremic mice. In dialysis patients, TBARS and lipid peroxidation were both significantly reduced in EX (65% and 12%, respectively, p< 0.05 for both), but did not change in SED, and there was a trend for a reduction in CRP levels in EX (p = 0.08), but not SED. Furthermore, the thickness of epicardial fat, a highly pro-inflammatory visceral fat depot related to cardiovascular disease risk, was also reduced in dialysis patients in EX (12%, p< 0.05), but not SED. CONCLUSIONS: These data suggest that endurance exercise training has modest or no effects on circulating markers of inflammation in either uremic mice or dialysis patients, possibly to the excessive inflammation in CKD, yet may still improve other factors related to inflammation and CVD risk in dialysis patients.