Irisin, a hormone secreted by myocytes induced in exercise, acts as a muscle-derived energy-expenditure signal that binds to undetermined receptors on the white adipose tissue surface, stimulating its browning and uncoupling protein 1 (UCP1) expression. The purpose of this study was to assess the effect of an intradialytic resistance exercise training program (RETP) on plasma irisin levels of hemodialysis (HD) patients and compare the baseline plasma irisin levels of HD patients to healthy subjects. This longitudinal study enrolled 26 patients undergoing HD (50% men, 44.8±14.1 years, body mass index (BMI) 23.5±3.9 kg/m²). The healthy subjects group consisted of 11 women and 7 men with mean age of 50.9±6.6 years and BMI, 24.2±2.7 kg/m². Anthropometric and biochemistry parameters (Irisin by Enzyme-Linked Immunosorbent Assay) were measured at the baseline and after 6 months of RETP (in both lower limbs). There was no difference regarding gender, age, and BMI between HD patients and healthy subjects. Plasma irisin levels in HD patients were lower than in healthy subjects (71.0±41.6 vs. 101.3±12.5 ng/ml, p<0.05). Although the muscle mass increased in consequence of exercise [evaluated by arm muscle area from 27.9 (24.1) to 33.1 (19.0) cm²], plasma irisin did not differ significantly after exercises (71.0±41.6 vs. 73.3±36.0 ng/ml). HD patients seem to have lower plasma irisin when compared to healthy subjects. Moreover, a resistance exercise training program was unable to augment plasma irisin despite increasing muscle mass.

Resistance exercise program for 6 months seems to be effective in reducing inflammation and PEW of HD patients. The universal trial number of this study is U1111-1139-1326.

The discussion about the optimal design of clinical trials reflects the perspectives of theory-based scientists and practice-based clinicians. Scientists compare the theory with published results. They observe a continuum from explanatory to pragmatic trials. Clinicians compare the problem they want to solve by completing a clinical trial with the results they can read in the literature. They observe a mixture of what they want and what they get. None of them can solve the problem without the support of the other. Here, we summarize the results of discussions with scientists and clinicians. All participants were interested to understand and analyze the arguments of the other side. As a result of this process, we conclude that scientists tell what they see, a continuum from clear explanatory to clear pragmatic trials. Clinicians tell what they want to see, a clear explanatory trial to describe the expected effects under ideal study conditions and a clear pragmatic trial to describe the observed effects under real-world conditions. Following this discussion, the solution was not too difficult. When we accept what we see, we will not get what we want. If we discuss a necessary change of management, we will end up with the conclusion that two types of studies are necessary to demonstrate efficacy and effectiveness. Efficacy can be demonstrated in an explanatory, ie, a randomized controlled trial (RCT) completed under ideal study conditions. Effectiveness can be demonstrated in an observational, ie, a pragmatic controlled trial (PCT) completed under real-world conditions. It is impossible to design a trial which can detect efficacy and effectiveness simultaneously. The RCTs describe what we may expect in health care, while the PCTs describe what we really observe.

Cumulative evidence indicates that oxidative stress and inflammation frequently occurs in patients undergoing maintenance hemodialysis (HD) and as a result of overproduction of reactive oxygen species (ROS) and a decrease of antioxidant defenses such as selenium (Se). Previous studies in our laboratory showed that the supplementation of 1 unit of Brazil nut (the richest known food source of Se) a day during 3 months is effective to improve Se status and increase glutathione peroxidase (GPx) levels in HD patients. The aim of this study was to evaluate the effect of Brazil nut supplementation on oxidative stress and inflammation markers in HD patients. Forty HD patients from Rio de Janeiro, Brazil were studied. All patients received one nut per day for 3 months. The Se plasma levels and GPx, 8-isoprostane, 8-hydroxy-2-deoxyguanosine (8-OHdG), and cytokine (TNF-α and IL-6) levels and lipid profile were determined before and after 3 months of supplementation. The plasma Se and GPx activity increased, while cytokines, 8-OHdG, and 8-isoprostane plasma levels decreased significantly after 3 months supplementation. HDL-c levels increased and LDL-c levels decreased significantly. These data suggest that the consumption of only one Brazil nut per day during 3 months was effective to reduce the inflammation, oxidative stress markers, and the atherogenic risk, thereby increasing the antioxidant defenses in HD patients. Our results indicate that Brazil nut as Se source plays an important role as an anti-inflammatory and antioxidant agent in HD patients.

Components present in the diet, L-carnitine, choline, and betaine are metabolized by gut microbiota to produce metabolites such as trimethylamine-N-oxide (TMAO) that appear to promote cardiovascular disease in chronic kidney disease (CKD) patients. The objective of this pilot study was to evaluate the effects of probiotic supplementation for 3 months on plasma TMAO levels in CKD patients on hemodialysis (HD). A randomized, double-blind trial was performed in 21 patients [54.8 ± 10.4 years, nine men, BMI 26.1 ± 4.8 kg/m, dialysis vintage 68.5 (34.2-120.7) months]. Ten patients were randomly allocated to the placebo group and 11 to the probiotic group [three capsules, totaling 9 × 10 colony-forming units per day of Streptococcus thermophilus (KB19), Lactobacillus acidophilus (KB27), and Bifidobacteria longum (KB31). Plasma TMAO, choline, and betaine levels were measured by LC-MS/MS at baseline and after 3 months. While TMAO did not change after probiotic supplementation, there was a significant increase in betaine plasma levels. In contrast, the placebo group showed a significant decrease in plasma choline levels. Short-term probiotic supplementation does not appear to influence plasma TMAO levels in HD patients. Long-term studies are needed to determine whether probiotics may affect TMAO production in CKD patients.

Low-protein diet is the recommended nutritional intervention for nondialysis chronic kidney disease (CKD) patients because excess protein intake can damage kidney function and produce uremic toxins. Some of these toxins are generated from amino acids breakdown by gut microbiota as p-cresyl sulfate and indoxyl sulfate that have been clearly associated with cardiovascular mortality in CKD patients. Another uremic toxin, trimethylamine N-oxide (TMAO), a degradation product of choline and L-carnitine (which come mainly from animal protein such as red meat and eggs) is now considered as a proatherogenic metabolite. In the present review, we will highlight the relationship between TMAO, diet and cardiovascular aspects, and the potential concerns about TMAO in nondialysis CKD patients.

No abstract

Marinho, SM, Moraes, C, Barbosa, JEdSM, Eduardo, JCC, Fouqe, D, Pelletier, S, and Mafra, D. Exercise training alters the bone mineral density of hemodialysis patients. J Strength Cond Res 30(10): 2918-2923, 2016-Patients with chronic kidney disease undergoing hemodialysis (HD) frequently present low bone mineral density (BMD), and exercise may be useful for treating bone loss. This study aimed to assess the effects of an intradialytic resistance exercise training program (RETP) on BMD in HD patients. Twenty-one patients were enrolled into 2 groups; 10 patients performed exercise (80.0% men; 46.9 ± 12.1 years; 27.0 ± 3.4 kg·m) and 11 patients were in the control group (54.5% men; 50.5 ± 11.5 years; 24.1 ± 8.7 kg·m). Dual-energy x-ray absorptiometry was used to measure the BMD, lean mass, and body fat before and after the supervised RETP (performed with elastic bands and ankle cuffs in both lower limbs 3 times a week for 24 weeks-72 sessions). In the exercise group, 30.0% of patients presented with osteopenia and 20.0% osteoporosis and in the control group, 45.5% osteopenia and 36.4% osteoporosis. Only in the exercise group, the osteoporosis percentage was reduced to 10.0% and the femoral neck BMD and T-score improved from 0.89 ± 0.1 to 0.93 ± 0.1 g·cm and from -1.3 ± 0.8 to -1.0 ± 0.8 g·cm (p ≤ 0.05), respectively, after the intervention. In contrast, these parameters were reduced in the control group. The results suggest that resistance exercise may be useful for improving the BMD in HD patients. In summary, 24 weeks of the supervised RETP played a role in improving the BMD of HD patients.