Exercise plus caloric restriction lowers soluble RAGE in adults with chronic kidney disease

Abstract

Introduction: The incidence of chronic kidney disease (CKD) has increased in recent years. CKD is associated with obesity, type 2 diabetes, and cardiovascular disease, although the mechanism remains unclear. Elevated soluble form of the receptor for advanced glycation end products ( RAGE) is related to proinflammatory signaling pathways that may promote diabetic nephropathy and vascular dysfunction. Because lifestyle modification reduces systematic inflammation in adults with obesity and hyperglycaemia, the hypothesis that exercise plus caloric restriction would lower soluble RAGE in adults with CKD was tested in this study. Methods: Eight adults (n = 6 females; age: 56.3 ± 2.8 y; BMI: 43.7 ± 2.2 kg/m 2 ; 2-h OGTT glucose: 215 ± 9.8 mg/dL; eGFR: 49.6 ± 3.3 mL/min/1.73 m 2 ) were enrolled in a 12-week pilot lifestyle intervention (supervised aerobic exercise [5 d/wk, up to 60 min/d at approximately 65%-85% HR max ] plus low-fat dietary counseling). Body composition (DXA), aerobic fitness (VO 2 max), insulin sensitivity (120 min 75 g OGTT; Matsuda Index), plasma levels of soluble RAGE and fetuin-A were measured before and after the intervention.Results: Exercise reduced body weight, fasting glucose, and fetuin-A as well as increased VO 2 max, glucose tolerance, and insulin sensitivity (all P < .05). Lifestyle intervention decreased plasma soluble RAGE (pre: 1018.1 ± 163 vs post: 810.6 ± 119.6 ng/mL; P = .02), and the decrease was associated with a lower 2-hour blood glucose (r = 0.76, P = .03) and with increased insulin sensitivity (r = −0.90, P < .01).Conclusions: Exercise and caloric restriction are effective at lowering soluble RAGE in relation to glucose regulation in patients with CKD.

NADH/NAD+ Redox Imbalance and Diabetic Kidney Disease

“…Such responses include AMPK activation, autophagy, ROS elimination, Nrf2 signaling pathway activation and enhancement of antioxidative capacity in the kidney [ 231 , 232 , 233 , 234 , 235 ]. In certain studies, exercise has been shown to have a synergistic effect on CR [ 236 , 237 ]. Therefore, CR and exercise may be applied simultaneously to enhance kidney function in diabetes [ 238 , 239 ].…”

Exercise tolls the bell for key mediators of low-grade inflammation in dysmetabolic conditions

“…In interventional models, training was indeed shown to efficiently decrease AGEs in obese-diabetic rodents [164,167]. Similarly, in humans, the practice of regular exercise was demonstrated to be effective in lowering AGEs levels in chronic inflammation [166] and soluble RAGEs in obese-dysglycemic patients [165] .…”

“…Exercise, by activating muscle glucose uptake, contributes to glucose balance and to enhance glycemic control in humans [163], blunting the formation of AGEs. The higher energy requirement, in trained organisms, diminishes the availability of glycating intermediates deriving from glycolytic (glucose-6-phosphate; fructose-6phosphate) and polyol (fructose-3-phosphate; 3-deoxyglucosone) pathways [13,164,165]. Higher levels of Inflammation and the activation of immune cells represent a potential trigger for the increase in oxidative stress.…”

Physical activity as a proxy to ameliorate inflammation in patients with type 2 diabetes and periodontal disease at high cardiovascular risk

“…The increased uptake and oxidation of circulating FFAs during exercise also contribute to reduce muscle and liver inflammation, and insulin resistance [35]. Lastly, regular exercise was shown to efficiently decrease AGEs in obese-diabetic animal models [68,79] and in humans [80]. AGEs production is mainly triggered by hyperglycemia and oxidative stress, and contributes to increase organ-specific and systemic inflammation [81].…”