Denise Mafra

Nutrition and chronic kidney disease.

The incidence of malnutrition disorders in chronic kidney disease (CKD) appears unchanged over time, whereas patient-care and dialysis techniques continue to progress. Despite some evidence for cost-effective treatments, there are numerous caveats to applying these research findings on a daily care basis. There is a sustained generation of data confirming metabolic improvement when patients control their protein intake, even at early stages of CKD. A recent protein-energy wasting nomenclature allows a simpler approach to the diagnosis and causes of malnutrition. During maintenance dialysis, optimal protein and energy intakes have been recently challenged, and there is no longer an indication to control hyperphosphatemia through diet restriction. Recent measurements of energy expenditure in dialysis patients confirm very low physical activity, which affects energy requirements. Finally, inflammation, a common state during CKD, acts on both nutrient intake and catabolism, but is not a contraindication to a nutritional intervention, as patients do respond and improve their survival as well as do noninflamed patients.

Nutritional strategies to modulate inflammation and oxidative stress pathways via activation of the master antioxidant switch Nrf2

The nuclear factor E2-related factor 2 (Nrf2) plays an important role in cellular protection against cancer, renal, pulmonary, cardiovascular and neurodegenerative diseases where oxidative stress and inflammation are common conditions. The Nrf2 regulates the expression of detoxifying enzymes by recognizing the human Antioxidant Response Element (ARE) binding site and it can regulate antioxidant and anti-inflammatory cellular responses, playing an important protective role on the development of the diseases. Studies designed to investigate how effective Nrf2 activators or modulators are need to be initiated. Several recent studies have shown that nutritional compounds can modulate the activation of Nrf2-Keap1 system. This review aims to discuss some of the key nutritional compounds that promote the activation of Nrf2, which may have impact on the human health.

Nrf2–keap1 system versus NF-κB: The good and the evil in chronic kidney disease?

Inflammation and oxidative stress are two major components involved in the atherogenic process generated by the innate immune response to lipoprotein peroxidation, which is accelerated in patients with chronic kidney disease (CKD). Whereas the redox-sensitive transcription factor nuclear factor-κB (NF-κB) plays an important role in the coordinated expression of inflammatory genes, the nuclear factor E2-related factor 2 (Nrf2) is the transcription factor that is responsible for both constitutive and inducible expression of antioxidant response element (ARE)-regulated genes. Thus, Nrf2 can regulate antioxidant and anti-inflammatory cellular responses of this system, playing an important protective role on the development of the uremic phenotype. This review describes the Nrf2 system and its possible role in CKD patients.

Use of handgrip strength in the assessment of the muscle function of chronic kidney disease patients on dialysis: a systematic review

BACKGROUND Even though handgrip strength (HGS) is considered a simple and reliable method to evaluate muscle function and, indirectly, the nutritional status in clinical settings, there is still no consensus concerning its use in patients with chronic kidney disease (CKD) undergoing dialysis. This study presents a systematic review of the literature on the use of HGS as a parameter for nutritional assessment and a prognostic marker in patients on dialysis. METHODS The MEDLINE database (1966 to October 2009) was consulted for this systematic review by using the search terms hand strength or muscle strength dynamometer and dialysis. Eighteen articles were identified and included in the analysis. RESULTS Similar to the general population, HGS values were associated with age and gender. The analysed studies showed correlation between muscle function estimated by HGS and variables used in the assessment of muscle mass and nutritional status, as well as the prediction of clinical complications. CONCLUSIONS The analysis indicates that HGS is a useful tool for continuous and systematic assessment of muscle mass related to nutritional status in patients on dialysis. However, it is still necessary to standardize the techniques used for HGS, especially with respect to the position of measurement, the evaluation period, the choice of arm side and the diagnostic criterion.

Body mass index, muscle and fat in chronic kidney disease: questions about survival

The human body can be roughly divided into two major compartments, fat mass and lean body mass. Adipose tissue is now considered to be a highly active tissue and, in addition to storing calories as triglycerides, it also secretes a large variety of compounds, including cytokines, chemokines and hormone-like factors such as leptin, adiponectin and resistin. On the other hand, muscle plays a central role in whole-body protein metabolism by serving as the principal provider for amino acids to maintain protein synthesis in vital tissues and organs and by providing hepatic gluconeogenic precursors. Although not a good indicator of body composition, the Quetelet index, also called body mass index (BMI), is often used for practical reasons. It is well known that high BMI predicts mortality and cardiovascular disease (CVD) in the general population. However, observational reports in the dialysis population have suggested that obesity is associated with improved survival, a phenomenon that is not well understood and subject to controversies. This review describes the characteristics of BMI in the general population and in chronic kidney disease (CKD) patients, as well as the respective role of muscle, whole body fat and fat distribution towards mortality, with particular emphasis on patients with CKD.

Role of altered intestinal microbiota in systemic inflammation and cardiovascular disease in chronic kidney disease

The normal intestinal microbiota plays a major role in the maintenance of health and disease prevention. In fact, the alteration of the intestinal microbiota has been shown to contribute to the pathogenesis of several pathological conditions, including obesity and insulin resistance, among others. Recent studies have revealed profound alterations of the gut microbial flora in patients and animals with chronic kidney disease (CKD). Alterations in the composition of the microbiome in CKD may contribute to the systemic inflammation and accumulation of gut-derived uremic toxins, which play a central role in the pathogenesis of accelerated cardiovascular disease and numerous other CKD-associated complications. This review is intended to provide a concise description of the potential role of the CKD-associated changes in the gut microbiome and its potential role the pathogenesis of inflammation and uremic toxicity. In addition, the potential efficacy of pre- and pro-biotics in the restoration of the microbiome is briefly described.

Probiotics and chronic kidney disease

Probiotics are the focus of a thorough investigation as a natural biotreatment due to their various health-promoting effects and inherent ability to fight specific diseases including chronic kidney disease (CKD). Indeed, intestinal microbiota has recently emerged as an important player in the progression and complications of CKD. Because many of the multifactorial physiological functions of probiotics are highly strain specific, preselection of appropriate probiotic strains based on their expression of functional biomarkers is critical. The interest in developing new research initiatives on probiotics in CKD have increased over the last decade with the goal of fully exploring their therapeutic potentials. The efficacy of probiotics to decrease uremic toxin production and to improve renal function has been investigated in in vitro models and in various animal and human CKD studies. However to date, the quality of intervention trials investigating this novel CKD therapy is still lacking. This review outlines potential mechanisms of action and efficacy of probiotics as a new CKD management tool, with a particular emphasis on uremic toxin production and inflammation.

Resistance exercise training does not affect plasma irisin levels of hemodialysis patients.

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.

Effect of Brazil nut supplementation on the blood levels of selenium and glutathione peroxidase in hemodialysis patients

OBJECTIVE In patients who have undergone hemodialysis, large amounts of reactive oxygen species (ROS) are produced and, at higher concentrations, ROS are thought to be involved in the pathogenesis of cardiovascular disease. It has been proposed that selenium (Se) may exert an antiatherogenic influence by reducing oxidative stress. The richest known food source of selenium is the Brazil nut (Bertholletia excelsa, family Lecythidaceae), found in the Amazon region. We evaluated the effect of Brazil nut supplementation on blood levels of Se and glutathione peroxidase (GSH-Px) activity in patients on hemodialysis. METHODS A total of 81 patients on hemodialysis (52.0±15.2 y old, average time on dialysis 82.3±91.4 mo, body mass index 24.9±4.4 kg/m(2)) from the RenalCor and RenalVida Clinics in Rio de Janeiro, Brazil, were studied. All patients received one nut (around 5 g, averaging 58.1 μg Se/g) a day for 3 mo. The Se concentrations in the nuts and in plasma and erythrocytes were determined by atomic absorption spectrophotometry with hydride generation (Hitachi, Z-500). GSH-Px levels were measured using Randox commercial kits. RESULTS Plasma Se (18.8±17.4 μg/L) and erythrocyte (72.4±37.9 μg/L) levels were below the normal range before nut supplementation. After supplementation, the plasma level increased to 104.0±65.0 μg/L and erythrocytes to 244.1±119.5 μg/L (P<0.0001). The activity of GSH-Px also increased after supplementation, from 46.6±14.9 to 55.9±23.6 U/g of hemoglobin (P<0.0001). Before supplementation, 11% of patients had GSH-Px activity below the normal range (27.5-73.6 U/g of hemoglobin). After supplementation, all patients showed GSH-Px activity within the normal range. CONCLUSION The data revealed that the investigated patients presented Se deficiency and that the consumption of only one Brazil nut a day (5 g) during 3 mo was effective to increase the Se concentration and GSH-Px activity in these patients, thus improving their antioxidant status.

Obestatin and ghrelin interplay in hemodialysis patients

OBJECTIVE Compounds involved in the regulation of appetite and body composition appear to be of interest in chronic kidney disease. The purpose of this study was to analyze plasma obestatin and acyl and des-acyl ghrelin in patients on hemodialysis (HD). METHODS Fifty patients on HD (56.0% women, mean age 62.2 ± 15.2 y) were studied. Blood samples were collected during fasting, before a regular HD session. Serum acyl and des-acyl ghrelin levels, leptin, and obestatin were measured using enzyme immunometric assay methods. Anthropometric parameters, appetite score, and food intake were recorded. RESULTS Patients showed elevated serum leptin (34.1 ± 30 ng/mL), normal acyl ghrelin (137 ± 116.5 pg/mL), high des-acyl ghrelin (670 ± 479 pg/mL), and low obestatin (2.0 ± 1.4 ng/mL) levels compared with healthy volunteers. According to body mass index (BMI), patients with a BMI >23 kg/m(2) had significantly lower plasma obestatin. In contrast, leptin levels were increased and acyl ghrelin tended to be higher in these patients. There was a strong positive correlation between obestatin and des-acyl ghrelin (r = 0.56, P = 0.0001) and inverse correlations between obestatin and BMI (r = -0.40, P = 0.007), waist circumference (r = -0.38, P = 0.024), and C-reactive protein (r = -0.29, P = 0.048). By multivariate analysis, obestatin was independently and positively correlated with des-acyl ghrelin (P = 0.01), but not with C-reactive protein, BMI, or waist circumference. CONCLUSION In summary, patients on HD exhibited increased plasma levels of des-acyl ghrelin, normal acyl ghrelin levels, and low obestatin levels. In lean patients, the obestatin and des-acyl ghrelin levels were increased, suggesting that these hormones may influence appetite and body composition in patients on HD.