Bicycle ergometer exercise during hemodialysis and its impact on quality of life, aerobic fitness and dialysis adequacy: A pilot study.

BACKGROUND: Chronic kidney disease patients on hemodialysis commonly have a worse quality of life (QoL) due to complications of the disease and dialysis procedure. Physical exercise has emerged as a strategy to improve this scenario. The objective of this study was to evaluate the effect of an intradialytic aerobic exercise program on QoL and aerobic fitness in hemodialysis patients. MATERIAL AND METHODS: These are a secondary analysis of clinical trial data previously published in which hemodialysis patients were randomized into "bike group" (using an adapted exercise bicycle) or "control group" (usual care). The exercise sessions lasted 45 min (5 min of warm-up, 35 min of moderate-intensity and 5 min of cool-down) three times/week for three months. The QoL domains were assessed using the SF-36 QoL questionnaire. Aerobic fitness was evaluated using the 6-min walk test (6MWT). Circulating cytokines, biochemical parameters and Kt/V were also assessed. RESULTS: Nine patients completed three months of exercise (5 men, 44 ± 11 years), and nine were in the control group (6 men, 44 ± 14 years). In the bike group, there was a trend to improve the physical role domain (p = 0.06) regarding QoL, an improvement in the 6MWT (p = 0.02), and in the Kt/V (p = 0.03) after three months. There was a positive correlation between the general health domain and Kt/V (r = 0.691; p = 0.003) and an inverse correlation between the physical functioning domain and plasma TNF-α levels (r = -0.514; p = 0.04). CONCLUSIONS: 12 weeks of intradialytic aerobic exercise was enough to benefit hemodialysis patients' quality of life, aerobic fitness, and quality of dialysis. CLINICALTRIALS: gov id: NCT04375553.

Uremic toxins levels from the gut microbiota seem not to be altered by physical exercise in hemodialysis patients.

PURPOSE: Regular physical exercise may result in many benefits to patients with chronic kidney disease (CKD) on hemodialysis (HD), including gut microbiota modulation and solute removal. The study aimed to evaluate the effects of two programs of intradialytic exercises on uremic toxins plasma levels in HD patients. METHODS: In experiment 1, twenty HD patients [12 men, 44.1 ± 8.9 years, BMI of 23.4 ± 2.4 kg/m2] were randomized into two groups: Aerobic exercise group (AEG, n = 11) that performed aerobic exercise on an adapted exercise bike three times a week for three months (36 sessions) and Control group (CG, n = 9). In experiment 2, twenty-six HD patients [19 men, 47.6 ± 11.0 years, BMI of 25.9 ± 3.6 kg/m2] were randomized into Resistance exercise group (REG, n = 14) that performed a resistance exercise program (using elastic bands and ankle cuffs with both lower limbs) monitored three times a week, during six months (72 sessions) and CG (n = 12). P-cresyl sulfate (p-CS), indoxyl sulfate (IS), and indol-3-acetic acid (IAA) plasma levels were determined by high-performance liquid chromatography (HPLC) with fluorescent detection. RESULTS: The uremic toxins plasma levels did not reduce in both exercise programs, aerobic exercise (IS: 32.7 ± 14.0 vs 33.0 ± 15.4 mg/L, p = 0.86; p-CS: 59.9 ± 39.3 vs 60.0 ± 41.2 mg/L, p = 0.99; IAA: 2233 [1488-2848] vs 2227 [1275-2824] µg/L, p = 0.72) and resistance exercise (IS: 28.3 ± 11.3 vs 29.1 ± 9.7 mg/L, p = 0.77; p-CS: 31.4 ± 21.3 vs 34.2 ± 19.8 mg/L, p = 0.63; IAA: 1628 [1330-3530] vs 2000 [971-3085] µg/L, p = 0.35) in HD patients. CONCLUSION: According to our findings, physical exercise does not appear to alter the levels of uremic toxins produced by the gut microbiota in HD patients.

Dietary intake of tyrosine and phenylalanine, and p-cresyl sulfate plasma levels in non-dialyzed patients with chronic kidney disease / Ingestão dietética de tirosina e fenilalanina e níveis plasmáticos de p-cresil sulfato em pacientes com doença renal crônica não dialisados

ABSTRACT Background: Patients with chronic kidney disease (CKD) present an imbalance of the gut microbiota composition, leading to increased production of uremic toxins like p-cresyl sulfate (PCS), product from bacterial fermentation of the amino acids tyrosine (Tyr) and phenylalanine (Phe) from the diet. Thus, diet may be a determinant in the uremic toxins levels produced by the gut microbiota. The aim of this study was to evaluate the possible relationship between Tyr and Phe intake and PCS plasma levels in non-dialysis CKD patients. Methods: Twenty-seven non-dialysis CKD patients (stages 3 and 4) without previous nutritional intervention were evaluated. The dietary intake was evaluated using a 24-hour recall, 3-day food record and protein intake was also estimated by Protein Nitrogen Appearance (PNA). The plasma levels of PCS were measured using reverse phase high performance liquid chromatography. Results: The evaluated patients (GRF, 34.8 ± 12.4 mL/min, 54.2 ± 14.3 years, BMI, 29.3 ± 6.1 kg/m2) presented mean protein intake of 1.1 ± 0.5 g/kg/day), Tyr of 4.5 ± 2.4 g/day and Phe of 4.6 ± 2.5 g/day. PCS plasma levels (20.4 ± 15.5 mg/L) were elevated and positively associated with both, Tyr (r = 0.58, p = 0.002) and Phe intake (r = 0.53, p = 0.005), even after adjustments for eGFR and age. Conclusion: This study suggests that the diet is an important modulator of the uremic toxins plasma levels produced by the gut microbiota, in non-dialysis CKD patients.

RESUMO Introdução: Pacientes com doença renal crônica (DRC) apresentam desequilíbrio na composição da microbiota intestinal, gerando toxinas urêmicas, como o p-cresil sulfato (PCS), pela fermentação bacteriana dos aminoácidos tirosina (Tyr) e fenilalanina (Phe) da dieta. Assim, a dieta pode ser determinante nos níveis de toxinas urêmicas produzidos pela microbiota intestinal. O objetivo deste estudo foi avaliar a possível relação entre a ingestão de Tyr e Phe e os níveis plasmáticos de PCS em pacientes com DRC não dialisados. Métodos: Foram avaliados 27 pacientes com DRC em tratamento conservador (estágios 3 e 4), sem intervenção nutricional prévia. A ingestão alimentar foi avaliada pelo recordatório alimentar de 24h (R-24h) de 3 dias, e a ingestão proteica também foi verificada através do Protein Nitrogen Appearance (PNA). Os níveis plasmáticos de PCS foram determinados por cromatografia líquida de fase reversa. Resultados: Os pacientes avaliados (TFG, 34,8 ± 12,4 mL/min, 54,2 ± 14,3 anos, IMC 29,3 ± 6,1 kg/m2) apresentaram ingestão média de proteína de 1,1 ± 0,5 g/kg/dia, Tyr de 4,5 ± 2,4 g/dia e Phe de 4,6 ± 2,5 g/dia. Os níveis plasmáticos de PCS (20,4 ± 15,5 mg/L) foram elevados e positivamente associados à ingestão de Tyr (r = 0,58, p = 0,002) e Phe (r = 0,53, p = 0,005), mesmo após ajustes pela TFG e idade. Conclusão: Este estudo sugere que a dieta é um importante modulador dos níveis plasmáticos de toxinas urêmicas produzidas pela microbiota intestinal em pacientes com DRC não dialisados.

Dietary intake of tyrosine and phenylalanine, and p-cresyl sulfate plasma levels in non-dialyzed patients with chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) present an imbalance of the gut microbiota composition, leading to increased production of uremic toxins like p-cresyl sulfate (PCS), product from bacterial fermentation of the amino acids tyrosine (Tyr) and phenylalanine (Phe) from the diet. Thus, diet may be a determinant in the uremic toxins levels produced by the gut microbiota. The aim of this study was to evaluate the possible relationship between Tyr and Phe intake and PCS plasma levels in non-dialysis CKD patients. METHODS: Twenty-seven non-dialysis CKD patients (stages 3 and 4) without previous nutritional intervention were evaluated. The dietary intake was evaluated using a 24-hour recall, 3-day food record and protein intake was also estimated by Protein Nitrogen Appearance (PNA). The plasma levels of PCS were measured using reverse phase high performance liquid chromatography. RESULTS: The evaluated patients (GRF, 34.8 ± 12.4 mL/min, 54.2 ± 14.3 years, BMI, 29.3 ± 6.1 kg/m2) presented mean protein intake of 1.1 ± 0.5 g/kg/day), Tyr of 4.5 ± 2.4 g/day and Phe of 4.6 ± 2.5 g/day. PCS plasma levels (20.4 ± 15.5 mg/L) were elevated and positively associated with both, Tyr (r = 0.58, p = 0.002) and Phe intake (r = 0.53, p = 0.005), even after adjustments for eGFR and age. CONCLUSION: This study suggests that the diet is an important modulator of the uremic toxins plasma levels produced by the gut microbiota, in non-dialysis CKD patients.

Effects of Low Protein Diet on Nuclear Factor Erythroid 2-Related Factor 2 Gene Expression in Nondialysis Chronic Kidney Disease Patients.

OBJECTIVE(S): Low protein diets (LPD; 0.6 g/kg/day), prescribed for nondialysis chronic kidney disease (CKD) patients, have demonstrated numerous benefits. LPDs may modulate inflammation and oxidative stress through the nuclear factor erythroid 2-related factor 2 (Nrf2), which encodes antioxidant and phase II detoxifying enzymes. LPDs also inhibit or antagonize nuclear factor kB (NF-kB) activity, which orchestrates inflammatory and oxidative stress responses. The objective of this study was to evaluate the effects of LPD on Nfr2 and NF-κB messenger RNA (mRNA) expression in nondialysis CKD patients. METHODS: In this longitudinal study, a LPD was prescribed for 30 nondialysis CKD patients for 6 months. Peripheral blood mononuclear cells were isolated, and quantitative real-time polymerase chain reaction analysis was performed to evaluate Nrf2, NF-κB, and NADPH quinine oxidoreductase-1 mRNA expression. Thiobarbituric acid-reactive substance (TBARS) levels, a marker of lipid peroxidation, were also evaluated. RESULTS: (Age 55.5 ± 14.0 years; body mass index 29.1 ± 5.9 kg/m2; glomerular filtration rate 35.6 ± 12.2 mL/minute). After 6 months of nutritional intervention, Nrf2 mRNA expression increased from 0.85 (0.47-1.56) to 1.28 (0.63-2.63) nmol/mL (P = .03), and TBARS levels were significantly decreased from 1.78 (1.31-2.38) to 1.30 (1.07-2.22) nmol/mL (P = .04). NF-κB mRNA expression showed no significant difference after 6 months, but the Nrf2/NF-κB ratio was increased. CONCLUSION(S): In this study, a LPD appeared to modulate Nrf2 expression and decrease the levels of TBARS in nondialysis CKD patients. However, more studies are needed to confirm the effectiveness of LPD on the modulation of transcription factors involved with oxidative stress and inflammation in nondialysis CKD patients.