Home-based versus center-based aerobic exercise on cardiopulmonary performance, physical function, quality of life and quality of sleep of overweight patients with chronic kidney disease.

BACKGROUND: The association between chronic kidney disease (CKD) and obesity can decrease the patients' cardiopulmonary capacity, physical functioning and quality of life. The search for effective and practical alternative methods of exercise to engage patients in training programs is of great importance. Therefore, we aimed to compare the effects of home-based versus center-based aerobic exercise on the cardiopulmonary and functional capacities, quality of life and quality of sleep of overweight non-dialysis-dependent patients with CKD (NDD-CKD). METHODS: Forty sedentary overweight patients CKD stages 3 and 4 were randomly assigned to an exercise group [home-based group (n = 12) or center-based exercise group (n = 13)] or to a control group (n = 15) that did not perform any exercise. Cardiopulmonary exercise test, functional capacity tests, quality of life, quality of sleep and clinical parameters were assessed at baseline, 12 and 24 weeks. RESULTS: The VO2peak and all cardiopulmonary parameters evaluated were similarly improved (p < 0.05) after 12 and 24 weeks in both exercise groups. The functional capacity tests improved during the follow-up in the home-based group (p < 0.05) and reached values similar to those obtained in the center-based group. The benefits achieved in both exercise groups were also reflected in improvement of quality of life and sleep (p < 0.05). No differences were observed between the exercise groups, and no changes in any of the parameters investigated were found in the control group. CONCLUSION: Home-based aerobic training was as effective as center-based training in improving the physical and functional capabilities, quality of life and sleep in overweight NDD-CKD patients.

Effect of Aerobic Exercise on Markers of Bone Metabolism of Overweight and Obese Patients With Chronic Kidney Disease.

OBJECTIVE: The aim of the study was to investigate the effect of aerobic exercise on markers of bone metabolism in overweight and obese nondialysis-dependent patients with chronic kidney disease. METHODS: This is a post-hoc study with 39 sedentary patients (55.5 ± 8.3 years, body mass index 31.2 ± 4.4 kg/m2, estimated glomerular filtration rate 26.9 ± 11.7 mL/minute) who were randomly assigned to the aerobic exercise group (n = 24) or the control group (n = 15). The aerobic training (walking) was prescribed according to ventilatory threshold and was performed 3 times per week during 24 weeks. Carboxylated and undercarboxylated osteocalcin (GLA and GLU), sclerostin and tartrate-resistant acid phosphatase isoform 5b (TRAP-5b), parathyroid hormone, total alkaline phosphatase (AP), body composition, cardiorespiratory, and functional capacity tests were measured at baseline and after the follow-up. RESULTS: At baseline, carboxylated osteocalcin (GLA) and undercarboxylated osteocalcin (GLU) were inversely correlated with estimated glomerular filtration rate (r = -0.64; r = -0.38, respectively). Both osteocalcin fragments were positively correlated with total AP (GLA: r = 0.36; GLU: r = 0.53). An inverse correlation was found between GLA and sclerostin with body fat (r = -0.36; r = -0.46, respectively). GLU was negatively correlated with markers of muscle mass (r = -0.34). TRAP-5b and sclerostin were inversely correlated with 6-minute walk test and time up and go test, respectively (r = -0.34; r = -0.35, respectively). After 24 weeks, all physical capacity parameters increased in the exercise group (P < .001). Except for total AP that increased after 24 weeks in the exercise group (P < .05), no other changes were observed in both groups in relation to the bone metabolism biomarkers investigated. CONCLUSION(S): In this post-hoc study, the aerobic training used did not promote relevant changes in the bone metabolism markers investigated.

Randomized controlled trial to evaluate the impact of aerobic exercise on visceral fat in overweight chronic kidney disease patients.

BACKGROUND: The prevalence of obesity has markedly increased in patients with chronic kidney disease (CKD). Studies on the impact of exercise focusing on obese CKD patients are scarce. Therefore, we aimed to investigate the effect of aerobic exercise performed either in an exercise centre or at home on visceral fat in overweight non-dialysed CKD patients. METHODS: Twenty-seven sedentary men (52.1 ± 9.5 years, body mass index 30.4 ± 3.8 kg/m(2), estimated glomerular filtration rate (eGFR) 27.5 ± 11.6 mL/min) were randomly assigned to a centre-based exercise group (n = 10), home-based exercise group (n = 8) or control group (n = 9). The aerobic training was prescribed according to ventilatory threshold and performed three times per week during 12 weeks. Body composition was assessed by dual energy X-ray absorptiometry (DEXA) and the distribution of abdominal fat by computed tomography. RESULTS: In the centre-based group, visceral fat and waist circumference decreased 6.4 ± 6.4 mm (P < 0.01) and 2.0 ± 2.3 cm (P = 0.03) and leg lean mass increased 0.5 ± 0.4 kg (P < 0.01). No significant changes were observed in the home-based group. Visceral fat increased 5.0 ± 4.4 mm in the control group (P = 0.01). In relation to the control, a group-by-time interaction was significant for visceral fat and waist circumference for both exercise groups and for leg lean mass for the centre-based group. Mean blood pressure decreased in both exercise groups (centre-based 13%, P < 0.01 and home-based 10%, P = 0.03) and eGFR increased 3.6 ± 4.6 mL/min (P = 0.03) in the centre-based group. These parameters remained unchanged in the control group. CONCLUSIONS: Centre-based aerobic exercise is an effective approach to reduce visceral fat besides promoting relevant clinical benefits in male overweight CKD patients.

New predictive equations to estimate resting energy expenditure of non-dialysis dependent chronic kidney disease patients.

BACKGROUND: Determination of resting energy expenditure (REE) is an important step for the nutritional and medical care of patients with chronic kidney disease (CKD). Methods such as indirect calorimetry or traditional predictive equations are costly or inaccurate to estimate REE of CKD patients. We aimed to develop and validate predictive equations to estimate the REE of non-dialysis dependent-CKD patients. METHODS: A database comprising REE measured by indirect calorimetry (mREE) of 170 non-dialysis dependent-CKD patients was used to develop (n = 119) and validate (n = 51) a new REE-predictive equation. Fat free mass (FFM) was assessed by anthropometry and by bioelectrical impedance (BIA). RESULTS: The multiple regression analysis generated three equations: (1) REE (kcal/day) = 854 + 7.4*Weight + 179*Sex - 3.3*Age + 2.1 *eGFR + 26 (if DM) (R2 = 0.424); (2) REE (kcal/day) = 678.3 + 14.07*FFM.ant + 54.8*Sex - 2*Age + 2.5*eGFR + 140.7* (if DM) (R2 = 0.449); (3) REE (kcal/day) = 668 + 17.1*FFM.BIA - 2.7*Age - 92.7*Sex + 1.3*eGFR - 152.3 (if DM) (R2 = 0.45). The estimated REE (eREE) was not different from the mREE (P = 0.181), a high ICC was found and the mean difference between mREE and eREE was not different from zero for the three equations in the validation group. eREE accuracy between 90 and 110% was observed in 55.3%, 62.5% and 61% of the patients for Eqs. (1), (2) and (3), respectively. CONCLUSION: The equations showed acceptable accuracy for REE prediction making them a valuable tool to support practitioners to provide more reliable energy recommendations for this group of patients.

Effect of Unripe Banana Flour on Gut-Derived Uremic Toxins in Individuals Undergoing Peritoneal Dialysis: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

In chronic kidney disease (CKD), the accumulation of gut-derived metabolites, such as indoxyl sulfate (IS), p-cresyl sulfate (pCS), and indole 3-acetic acid (IAA), has been associated with the burden of the disease. In this context, prebiotics emerge as a strategy to mitigate the accumulation of such compounds, by modulating the gut microbiota and production of their metabolites. The aim of this study was to evaluate the effect of unripe banana flour (UBF-48% resistant starch, a prebiotic) on serum concentrations of IS, pCS, and IAA in individuals undergoing peritoneal dialysis (PD). A randomized, double-blind, placebo-controlled, crossover trial was conducted. Forty-three individuals on PD were randomized to sequential treatment with UBF (21 g/day) and placebo (waxy corn starch-12 g/day) for 4 weeks, or vice versa (4-week washout). The primary outcomes were total and free serum levels of IS, pCS, and IAA. Secondary outcomes were 24 h urine excretion and dialysis removal of IS, pCS, and IAA, serum inflammatory markers [high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α)], serum lipopolysaccharide LPS, and dietary intake. Of the 43 individuals randomized, 26 completed the follow-up (age = 55 ± 12 years; 53.8% men). UBF did not promote changes in serum levels of IS (p = 0.70), pCS (p = 0.70), and IAA (p = 0.74). Total serum IS reduction was observed in a subgroup of participants (n = 11; placebo: median 79.5 µmol/L (31-142) versus UBF: 62.5 µmol/L (31-133), p = 0.009) who had a daily UBF intake closer to that proposed in the study. No changes were observed in other secondary outcomes. UBF did not promote changes in serum levels of IS or pCS and IAA; a decrease in IS was only found in the subgroup of participants who were able to take 21g/day of the UBF.

Estimating resting energy expenditure of patients on dialysis: Development and validation of a predictive equation.

OBJECTIVES: The aims of this study were to develop and validate a resting energy expenditure (REE) predictive equation in a cohort of patients on dialysis and to test the accuracy of two previously developed specific equations to estimate REE of these patients. METHODS: A database with REE measured by indirect calorimetry (IC) of 189 patients on hemodialysis and peritoneal dialysis was used to develop and validate the new equation. The sample including only patients on hemodialysis (n = 131) was used to test the accuracy of the specific REE dialysis equations by Vilar and Byham-Gray. RESULTS: Multiple regression analysis generated two equations: REE (kcal/d) = 957.02 - 8.08 × age + 11.07 × body weight + 136.4 (if men) (R2 = 0.515) (1) REE (kcal/d) = 624.6-4.8 × age + 20.6 × fat-free, ass-fat-free mass-8.65 (if men) (R2 = 0.512) (2) In the validation group, REE by both equations did not differ from the REE measured by IC. No bias was found in the Bland-Altman analysis and the intraclass correlation coefficient and P20 test showed good reliability with measured REE. Vilar's equation overestimated REE; whereas REE generated by Byham-Gray's equation did not differ from measured REE. Proportional and systematic biases were significant for both equations. CONCLUSIONS: The new equations developed showed good accuracy and can be valuable to estimate energy needs of patients on dialysis. Byham-Gray's and Vilar's equations presented low to moderate performance to estimate REE of the patients on dialysis.

In vitro effect of uremic serum on barrier function and inflammation in human colonocytes.

INTRODUCTION: In chronic kidney disease (CKD), it has been suggested that alterations within the gut are associated with an inflammatory state and uremic toxicity. Studies suggest that uremia may impair the function of the intestinal barrier via the promotion of increased intestinal permeability. To understand the mechanisms that are involved in intestinal barrier damage in the setting of uremia, we evaluated the in vitro effect of uremic serum on transepithelial electrical resistance (TER), inflammation, and apoptosis in intestinal epithelial cells (T84). METHODS: Pools of serum from healthy individuals, patients not on dialysis, and patients on hemodialysis (Pre-HD and Post-HD) were prepared. T84 cells were incubated for 24 h in medium, of which 10% consisted of the pooled serum from each group. After incubation, the TER was measured and the following parameters were determined by flow cytometry: expression of toll-like receptors (TLRs), production of reactive oxygen species (ROS), and apoptosis. The level of IL-6 in the culture supernatant was determined by ELISA. RESULTS: No difference was observed among the groups with respect to TER, apoptosis, and ROS or the expression of TLR-2, TLR-4, and TLR-9. IL-6 secretion was higher (p < 0.001) in cells that were incubated with pre- and post-HD serum. CONCLUSION: The results that were obtained from this model suggest that uremic serum per se does not seem to impair the integrity of intestinal epithelial cells. The increased IL-6 secretion by cells that were incubated with HD serum suggests a potential effect of uremia in the intestinal inflammatory response.

Effect of cholecalciferol on vitamin D-regulatory proteins in monocytes and on inflammatory markers in dialysis patients: A randomized controlled trial.

BACKGROUND & AIMS: Hypovitaminosis D and inflammation are highly prevalent among patients undergoing dialysis, and the association of both conditions with worse survival has been well recognized. Although a potential role for vitamin D in the immune system has been suggested, the effect of the treatment of hypovitaminosis D on the modulation of the inflammatory response remains unclear. The aim of this study was to investigate the effect of the restoration of the vitamin D status on the expression of vitamin D-regulatory proteins in monocytes and on circulating inflammatory markers in dialysis patients. METHODS: In this randomized double-blind placebo-controlled 12-week trial, 38 patients on dialysis with serum 25-hydroxyvitamin D [25(OH)D] <20 ng/mL were randomized either to the cholecalciferol group (n = 20; 50,000 IU of cholecalciferol twice weekly) or to the control group (n = 18; 50 drops of a placebo solution twice weekly). The expression of vitamin D receptor (VDR), CYP27B1, CYP24A1 and interleukin-6 (IL-6) in monocytes was determined by flow cytometry. Serum concentrations of 25(OH)D, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were measured. The trial is registered at ClinicalTrials.gov #NCT01974245. RESULTS: After 12 weeks, the serum 25(OH)D increased from 14.3 ± 4.7 ng/mL to 43.1 ± 11.0 ng/mL (p < 0.05) in the cholecalciferol group and did not change in the control group (13.9 ± 4.2 ng/mL to 13.5 ± 4.3 ng/mL; p = 0.56). In monocytes, while CYP27B1 expression and VDR expression increased in the cholecalciferol group (p < 0.05), CYP27B1 expression did not change, and VDR expression decreased in the control group (p < 0.05). There were no changes in IL-6 and CYP24A1 expression in both groups. Serum concentration of IL-6 and CRP decreased from 8.1 ± 6.6 pg/mL to 4.6 ± 4.1 pg/mL (p < 0.05) and from 0.50 (0.10-1.27) mg/dL to 0.28 (0.09-0.62) mg/dL (p < 0.05), respectively only in the cholecalciferol group. Assessed overtime, the treatment group differences in 25(OH) D, PTH, CRP and IL-6, CYP27B1 and VDR remained significant. CONCLUSIONS: Restoration of vitamin D status of patients undergoing dialysis promoted upregulation of CYP27B1 and VDR expression in monocytes and a decrease in circulating inflammatory markers.

Impact of home-based aerobic exercise on the physical capacity of overweight patients with chronic kidney disease.

BACKGROUND: Home-based exercise has been shown to provide benefits in terms of physical capacity in the general population, but has been scarcely investigated in patients with chronic kidney disease (CKD). AIMS: To evaluate the impact of a home-based aerobic training on the cardiopulmonary and functional capacities of overweight non-dialysis-dependent patients with CKD (NDD-CKD). METHODS: Twenty-nine sedentary patients (55.1 ± 11.6 years, BMI = 31.2 ± 6.1 kg/m(2), eGFR = 26.9 ± 17.4 mL/min/1.73 m(2)) were randomly assigned to a home-based exercise group (n = 14) or to a control group (n = 15) that remained without performing exercise. Aerobic training was performed three times per week for 12 weeks. A cardiopulmonary exercise test, functional capacity and clinical parameters were evaluated. RESULTS: A significant increase, ranging from 8.3 to 17 %, was observed in the cardiopulmonary capacity parameters, such as maximal ventilation (p = 0.005), VO2peak (p = 0.049), ventilatory threshold (p = 0.040) and respiratory compensation point (p < 0.001), of the exercise group. A simultaneous improvement in the functional capacity tests [6-min walk test (p < 0.001), time up and go test (p < 0.001), arm curl test (p < 0.001), sit and stand test (p < 0.001), 2-min step test (p < 0.001) and back scratch test (p = 0.042)] was also found in patients who were submitted to the exercise. Exercised patients experienced a decrease in systolic and diastolic blood pressure, average 10.6 % (p < 0.001) and 9.2 % (p = 0.007), respectively, and a trend toward improved renal function (p = 0.1). No change in any parameter was found in the control group during the follow-up. CONCLUSION: The home-based aerobic exercise program was feasible, safe and effective for the improvement in the cardiopulmonary and functional capacities of overweight NDD-CKD patients.

In vitro effect of uremic serum on barrier function and inflammation in human colonocytes / Efeito in vitro do soro urêmico sobre a função de barreira e inflamação em colonócitos humanos

ABSTRACT Introduction: In chronic kidney disease (CKD), it has been suggested that alterations within the gut are associated with an inflammatory state and uremic toxicity. Studies suggest that uremia may impair the function of the intestinal barrier via the promotion of increased intestinal permeability. To understand the mechanisms that are involved in intestinal barrier damage in the setting of uremia, we evaluated the in vitro effect of uremic serum on transepithelial electrical resistance (TER), inflammation, and apoptosis in intestinal epithelial cells (T84). Methods: Pools of serum from healthy individuals, patients not on dialysis, and patients on hemodialysis (Pre-HD and Post-HD) were prepared. T84 cells were incubated for 24 h in medium, of which 10% consisted of the pooled serum from each group. After incubation, the TER was measured and the following parameters were determined by flow cytometry: expression of toll-like receptors (TLRs), production of reactive oxygen species (ROS), and apoptosis. The level of IL-6 in the culture supernatant was determined by ELISA. Results: No difference was observed among the groups with respect to TER, apoptosis, and ROS or the expression of TLR-2, TLR-4, and TLR-9. IL-6 secretion was higher (p < 0.001) in cells that were incubated with pre- and post-HD serum. Conclusion: The results that were obtained from this model suggest that uremic serum per se does not seem to impair the integrity of intestinal epithelial cells. The increased IL-6 secretion by cells that were incubated with HD serum suggests a potential effect of uremia in the intestinal inflammatory response.

RESUMO Introdução: Tem sido sugerido que na doença renal crônica (DRC) a uremia pode causar alterações intestinais, tais como modificações na microbiota e danos à barreira intestinal, e que estas possíveis alterações podem ter uma relação importante com o estado inflamatório e a toxicidade urêmica apresentadas por pacientes com DRC. Objetivos: Avaliar o efeito in vitro do soro urêmico sobre a permeabilidade da monocamada de células epiteliais do intestino, inflamação e apoptose. Métodos: Pools de soro foram preparados a partir de soros de indivíduos saudáveis, pacientes em tratamento conservador e em hemodiálise (Pré e Pós-HD). As células T84 foram incubadas por 24 horas com os diferentes pools. Em seguida a TER foi medida e as células foram submetidas às seguintes análises: apoptose, produção de espécies reativas de oxigênio (EROs) e expressão de receptores toll-like (TLR) por citometria de fluxo e detecção de IL-6 no sobrenadante da cultura por ELISA. Resultados: Não foram encontradas diferenças, entre os grupos, com relação a TER, apoptose, EROs e expressão de TLR-2, TLR-4 e TLR-9. Já a secreção de IL-6 foi maior (p < 0,001) pelas células incubadas com soro pré-HD e pós-HD. Conclusão: Os resultados obtidos a partir deste modelo sugerem que a uremia per se parece não comprometer a integridade das células epiteliais do intestino. O aumento da secreção de IL-6 pelas células incubadas com soro HD (pré e pós) sugere um potencial efeito da uremia sobre a resposta inflamatória intestinal.

Impact of training at ventilatory threshold on cardiopulmonary and functional capacity in overweight patients with chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD) and obesity are both associated with reduced physical capacity. The potential benefit of aerobic training on physical capacity has been recognized. The exercise intensity can be established using different methods mostly subjective or indirect. Ventilatory threshold (VT) is a direct and objective method that allows prescribing exercise intensity according to individual capacity. OBJECTIVES: To evaluate the impact of aerobic training at VT intensity on cardiopulmonary and functional capacities in CKD patients with excess of body weight. METHODS: Ten CKD patients (eight men, 49.7 ± 10.1 years; BMI 30.4 ± 3.5 kg/m², creatinine clearance 39.4 ± 9.8 mL/min/1.73 m²) underwent training on a treadmill three times per week during 12 weeks. Cardiopulmonary capacity (ergoespirometry), functional capacity and clinical parameters were evaluated. RESULTS: At the end of 12 weeks, VO2PEAK increased by 20%, and the speed at VO2PEAK increased by 16%. The training resulted in improvement in functional capacity tests, such as six-minute walk test (9.2%), two-minute step test (20.3%), arm curl test (16.3%), sit and stand test (35.7%), and time up and go test (15.3%). In addition, a decrease in systolic and diastolic blood pressures was observed despite no change in body weight, sodium intake and antihypertensive medication. CONCLUSION: Aerobic exercise performed at VT intensity improved cardipulmonary and functional capacities of overweight CKD patients. Additional benefit on blood pressure was observed. These results suggest that VT can be effectively applied for prescribing exercise intensity in this particular group of patients.

Impact of training at ventilatory threshold on cardiopulmonary and functional capacity in overweight patients with chronic kidney disease / Exercício aeróbico baseado no primeiro limiar ventilatório em pacientes com excesso de peso e doença renal crônica: impacto sobre a capacidade cardiorrespiratória e funcional

INTRODUCTION: Chronic kidney disease (CKD) and obesity are both associated with reduced physical capacity. The potential benefit of aerobic training on physical capacity has been recognized. The exercise intensity can be established using different methods mostly subjective or indirect. Ventilatory threshold (VT) is a direct and objective method that allows prescribing exercise intensity according to individual capacity. OBJECTIVES: To evaluate the impact of aerobic training at VT intensity on cardiopulmonary and functional capacities in CKD patients with excess of body weight. METHODS: Ten CKD patients (eight men, 49.7 ± 10.1 years; BMI 30.4 ± 3.5 kg/m², creatinine clearance 39.4 ± 9.8 mL/min/1.73 m²) underwent training on a treadmill three times per week during 12 weeks. Cardiopulmonary capacity (ergoespirometry), functional capacity and clinical parameters were evaluated. RESULTS: At the end of 12 weeks, VO2PEAK increased by 20%, and the speed at VO2PEAK increased by 16%. The training resulted in improvement in functional capacity tests, such as six-minute walk test (9.2%), two-minute step test (20.3%), arm curl test (16.3%), sit and stand test (35.7%), and time up and go test (15.3%). In addition, a decrease in systolic and diastolic blood pressures was observed despite no change in body weight, sodium intake and antihypertensive medication. CONCLUSION: Aerobic exercise performed at VT intensity improved cardipulmonary and functional capacities of overweight CKD patients. Additional benefit on blood pressure was observed. These results suggest that VT can be effectively applied for prescribing exercise intensity in this particular group of patients.

INTRODUÇÃO: O excesso de peso e a doença renal crônica (DRC) estão associados à baixa capacidade cardiorrespiratória (CR) e funcional (CF). Já foi observado que o treinamento aeróbico (TA) melhora a CR e CF. Métodos indiretos e subjetivos são comumente empregados para a prescrição da intensidade do TA. O limiar ventilatório (LV) é um método direto e objetivo que permite prescrever a intensidade do TA de acordo com a capacidade física do paciente. OBJETIVOS: Avaliar o impacto do TA com base na intensidade do LV sobre a CR e CF de pacientes com excesso de peso e portadores de DRC na fase não dialítica. MÉTODOS: Dez pacientes (oito homens; 49 ± 10,1 anos, IMC 30,4 ± 3,5 kg/m² , depuração de creatinina 39,4 ± 9,8 mL/min/1,73m²) foram submetidos à TA 3 vezes por semana durante 12 semanas. CR (ergoespirometria), CF e parâmetros clínicos foram avaliados. RESULTADOS: O TA promoveu aumento de 20% no consumo pico de O2 (VO2PICO), 16% na velocidade alcançada no VO2PICO e melhora em 9,2% na caminhada de seis minutos, 20,3% na marcha estacionária, 35,7% no sentar e levantar, 16,3% na resistência muscular de membro superior e 15,3% no tempo de ir e voltar. A pressão arterial diminuiu sem modificação nos anti-hipertensivos, no peso ou no consumo de sódio. CONCLUSÃO: Os resultados indicam que o TA baseado na intensidade do LV melhora a CR, CF e pressão arterial de pacientes portadores de DRC com excesso de peso. Isso sugere que o TA baseado na intensidade LV é eficaz e pode ser empregado com segurança nesses pacientes.