Metabolic Effects of Diet and Exercise in Patients with Moderate to Severe CKD: A Randomized Clinical Trial

Abstract

CKD is steadily increasing along with obesity worldwide. Furthermore, obesity is a proinflammatory risk factor for progression of CKD and cardiovascular disease. We tested the hypothesis that implementation of caloric restriction and aerobic exercise is feasible and can improve the proinflammatory metabolic milieu in patients with moderate to severe CKD through a pilot, randomized, 2×2 factorial design trial. Of 122 participants consented, 111 were randomized to receive caloric restriction and aerobic exercise, caloric restriction alone, aerobic exercise alone, or usual care. Of those randomized, 42% were women, 25% were diabetic, and 91% were hypertensive; 104 started intervention, and 92 completed the 4-month study. Primary outcomes were a change from baseline in absolute fat mass, body weight, plasma F-isoprostane concentrations, and peak oxygen uptake (VO). Compared with usual care, the combined intervention led to statistically significant decreases in body weight and body fat percentage. Caloric restriction alone also led to significant decreases in these measures, but aerobic exercise alone did not. The combined intervention and each independent intervention also led to significant decreases in F-isoprostane and IL-6 concentrations. No intervention produced significant changes in VO, kidney function, or urine albumin-to-creatinine ratio. In conclusion, 4-month dietary calorie restriction and aerobic exercise had significant, albeit clinically modest, benefits on body weight, fat mass, and markers of oxidative stress and inflammatory response in patients with moderate to severe CKD. These results suggest healthy lifestyle interventions as a nonpharmacologic strategy to improve markers of metabolic health in these patients.

Bioactive food and exercise in chronic kidney disease: Targeting the mitochondria

“…A recent study in patients with moderate‐to‐severe CKD investigated the effect of caloric restriction, aerobic exercise (alternating treadmill, elliptical cross‐trainer, Nu‐Step cross‐trainer and recumbent stationary bicycle) or a combination of interventions during a 4‐month period. All groups displayed reduced oxidative stress although the combined intervention (diet + exercise) proved most efficient . These findings suggest that such interventions could ameliorate mitochondrial dysfunction.…”

“…All groups displayed reduced oxidative stress although the combined intervention (diet + exercise) proved most efficient. 107 These findings suggest that such interventions could ameliorate mitochondrial dysfunction.…”

Obesity as a barrier to kidney transplantation: Time to eliminate the body weight bias?

“…More modest weight loss has been recorded with lifestyle approaches including dietary intervention with or without exercise. Weight management approaches in the CKD population are most frequently assessed prior to dialysis and appear to promote weight loss in a range of 2%‐10%, sustained for up to 24 months . In this weight loss range, several studies have demonstrated improved metabolic health .…”

“…Weight management approaches in the CKD population are most frequently assessed prior to dialysis and appear to promote weight loss in a range of 2%-10%, sustained for up to 24 months. 25,26 In this weight loss range, several studies have demonstrated improved metabolic health. 25,26 However, this field is limited by small RCTs with high risk of bias, with limited focus on transplant listing as outcomes.…”

Dietary intake regulates the circulating inflammatory monocyte pool

“…Clinical studies performed in overweight or obese individuals undergoing caloric restriction showed a reduction of pro-inflammatory cytokines in the blood (Ho et al, 2015;Ikizler et al, 2018;Imayama et al, 2012;Loria-Kohen et al, 2013;Oh et al, 2013;Ott et al, 2017;Ramel et al, 2010;Tajik et al, 2013), and diet-induced weight loss has a superior 20 benefit on patient systemic inflammation compared to interventional weight loss due to gastric bypass surgery (Lips et al, 2016). Although little data is available on the effect of caloric restriction on inflammation in normal-weight individuals, prior studies have shown that individuals undergoing intermittent or religious fasting have reduced basal levels of circulating pro-inflammatory cytokines including TNFα, IL-6, and IL-1β (Aksungar et al,25 2007; Faris et al, 2012;Moro et al, 2016).…”