ABSTRACT
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.
Subject(s)
Humans , Phenylalanine , Tyrosine , Diet , Renal Insufficiency, Chronic , Indican , Sulfates , Sulfuric Acid Esters , Cresols , EatingABSTRACT
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.
Subject(s)
Diet , Indican , Phenylalanine , Renal Insufficiency, Chronic , Tyrosine , Cresols , Eating , Humans , Sulfates , Sulfuric Acid EstersABSTRACT
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.
Subject(s)
Diet, Protein-Restricted/methods , Gene Expression/genetics , NF-E2-Related Factor 2/blood , NF-E2-Related Factor 2/genetics , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/genetics , Female , Humans , Longitudinal Studies , Male , Middle AgedABSTRACT
ABSTRACT Introduction: Chronic Kidney disease (CKD) patients have a high prevalence of cardiovascular mortality, and among the risk factors are dyslipidemia and obesity, common findings in the early stages of CKD. The aim of this study was to evaluate the effects of low protein diet (LPD) on the lipid and anthropometric profile in non-dialysis CKD patients. Methods: Forty CKD patients were studied (20 men, 62.7 ± 15.2 years, glomerular filtration rate (GFR) 26.16 ± 9.4 mL/min/1.73m2). LPD (0.6g/kg/d) was prescribed for six months and, biochemical and anthropometric parameters like body mass index (BMI), waist circumference and body fat mass (assessed by dual X-ray absorptiometry - DXA) were evaluated before and after six months with LPD. Results: After six months of nutritional intervention, patients presented reduction on BMI (from 28.1 ± 5.6 to 27.0 ± 5.3 Kg/m2, p = 0.001), total cholesterol (from 199.7 ± 57.1 to 176.0 ± 43.6mg/dL, p = 0.0001), LDL (from 116.2 ± 48.1 to 97.4 ± 39.1 mg/dL, p = 0,001) and uric acid (from 6.8 ± 1.4 to 6.2 ± 1.3 mg/dL, p = 0.004). In addition, GFR values were increased from 26.2 ± 9.5 to 28.9 ± 12.7mL/min (p = 0.02). The energy, proteins, cholesterol and fiber intake were reduced significantly. Conclusion: LPD prescribe to non-dialysis CKD patients for six months was able to improve some cardiovascular risk factors as overweight and plasma lipid profile, suggesting that LPD can be also an important tool for protection against cardiovascular diseases in these patients.
RESUMO Introdução: Pacientes com Doença Renal Crônica (DRC) possuem alta prevalência de mortalidade cardiovascular e, dentre os fatores de risco, encontram-se alterações no perfil lipídico e excesso de peso, que são achados comuns na DRC. O objetivo deste estudo foi avaliar os efeitos da dieta hipoproteica sobre o perfil antropométrico e lipídico de pacientes com DRC em tratamento conservador. Métodos: Foram estudados 40 pacientes com DRC (20 homens, 62,7 ± 15,2 anos, e Taxa de Filtração Glomerular (TFG) de 26,2 ± 9,4 mL/min/1,73m2). Os pacientes receberam prescrição de dieta hipoproteica (0,6g/kg/d) e parâmetros bioquímicos e antropométricos como índice de massa corporal (IMC), circunferência da cintura (CC) e percentual de gordura corporal (GC) avaliado por absorciometria com raio-x de dupla energia (DXA), foram analisados antes e após 6 meses de intervenção. Resultados: Os pacientes apresentaram após 6 meses, redução do IMC (de 28,1 ± 5,6 para 27,0 ± 5,3Kg/m2, p = 0,001), colesterol total (de 199,7 ± 57,1 para 176,0 ± 43,6mg/dL, p = 0,0001), LDL (de 116,2 ± 48,1 para 97,4 ± 39,1 mg/dL, p = 0,001) e ácido úrico (de 6,8 ± 1,4 para 6,2 ± 1,3 mg/dL, p = 0,004) e, aumento da TFG de 26,2 ± 9,5 para 28,9 ± 12,7mL/min (p = 0,02). Houve redução significativa na ingestão de energia e proteínas, bem como de colesterol e fibras. Conclusão: A intervenção com dieta hipoproteica para pacientes com DRC em tratamento conservador por seis meses foi capaz de melhorar alguns fatores de risco cardiovascular, como o excesso de peso e o perfil lipídico plasmático, sugerindo que a dieta hipoproteica, além de outros benefícios pode também ser importante ferramenta para a proteção de doenças cardiovasculares nesses pacientes.
Subject(s)
Humans , Male , Female , Middle Aged , Cholesterol/blood , Diet, Protein-Restricted , Body Size , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/therapy , Conservative Treatment , Triglycerides/bloodABSTRACT
INTRODUCTION: Chronic Kidney disease (CKD) patients have a high prevalence of cardiovascular mortality, and among the risk factors are dyslipidemia and obesity, common findings in the early stages of CKD. The aim of this study was to evaluate the effects of low protein diet (LPD) on the lipid and anthropometric profile in non-dialysis CKD patients. METHODS: Forty CKD patients were studied (20 men, 62.7 ± 15.2 years, glomerular filtration rate (GFR) 26.16 ± 9.4 mL/min/1.73m2). LPD (0.6g/kg/d) was prescribed for six months and, biochemical and anthropometric parameters like body mass index (BMI), waist circumference and body fat mass (assessed by dual X-ray absorptiometry - DXA) were evaluated before and after six months with LPD. RESULTS: After six months of nutritional intervention, patients presented reduction on BMI (from 28.1 ± 5.6 to 27.0 ± 5.3 Kg/m2, p = 0.001), total cholesterol (from 199.7 ± 57.1 to 176.0 ± 43.6mg/dL, p = 0.0001), LDL (from 116.2 ± 48.1 to 97.4 ± 39.1 mg/dL, p = 0,001) and uric acid (from 6.8 ± 1.4 to 6.2 ± 1.3 mg/dL, p = 0.004). In addition, GFR values were increased from 26.2 ± 9.5 to 28.9 ± 12.7mL/min (p = 0.02). The energy, proteins, cholesterol and fiber intake were reduced significantly. CONCLUSION: LPD prescribe to non-dialysis CKD patients for six months was able to improve some cardiovascular risk factors as overweight and plasma lipid profile, suggesting that LPD can be also an important tool for protection against cardiovascular diseases in these patients.
Subject(s)
Body Size , Cholesterol/blood , Conservative Treatment , Diet, Protein-Restricted , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/therapy , Triglycerides/blood , Female , Humans , Male , Middle AgedABSTRACT
OBJECTIVES: To evaluate the effects of low-protein diet (LPD) on uremic toxins and the gut microbiota profile in nondialysis chronic kidney disease (CKD) patients. DESIGN AND METHODS: Longitudinal study with 30 nondialysis CKD patients (stage 3-4) undergoing LPD for 6 months. Adherence to the diet was evaluated based on the calculation of protein equivalent of nitrogen appearance from the 24-hour urine analysis. Good adherence to LPD was considered when protein intake was from 90% to 110% of the prescribed amount (0.6 g/kg/day). Food intake was analyzed by the 24-hour recall method. The anthropometric, biochemical and lipid profile parameters were measured according to standard methods. Uremic toxin serum levels (indoxyl sulfate, p-cresyl sulfate, indole-3-acetic acid) were obtained by reversed-phase high-performance liquid chromatography (RP-HPLC). Fecal samples were collected to evaluate the gut microbiota profile through polymerase chain reaction and denaturing gradient gel electrophoresis. Statistical analysis was performed by the SPSS 23.0 program software. RESULTS: Patients who adhered to the diet (n = 14) (0.7 ± 0.2 g/kg/day) presented an improvement in renal function (nonsignificant) and reduction in total and low-density lipoprotein cholesterol (183.9 ± 48.5-155.7 ± 37.2 mg/dL, P = .01; 99.4 ± 41.3-76.4 ± 33.2 mg/dL, P = .01, respectively). After 6 months of nutricional intervention, p-cresyl sulfate serum levels were reduced significantly in patients who adhered to the LPD (19.3 [9.6-24.7] to 15.5 [9.8-24.1] mg/L, P = .03), and in contrast, the levels were increased in patients who did not adhere (13.9 [8.0-24.8] to 24.3 [8.1-39.2] mg/L, P = .004). In addition, using the denaturing gradient gel electrophoresis technique, it was observed change in the intestinal microbiota profile after LPD intervention in both groups, and the number of bands was positively associated with protein intake (r = 0.44, P = .04). CONCLUSION: LPD seems be a good strategy to reduce the uremic toxins production by the gut microbiota in nondialysis CKD patients.
Subject(s)
Cresols/blood , Diet, Protein-Restricted , Gastrointestinal Microbiome/physiology , Indican/blood , Indoleacetic Acids/blood , Renal Insufficiency, Chronic/diet therapy , Sulfuric Acid Esters/blood , Adult , Aged , Feces/microbiology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Patient Compliance , Renal Insufficiency, Chronic/bloodABSTRACT
Red meat is an important dietary source of high biological value protein and micronutrients such as vitamins, iron, and zinc that exert many beneficial functions. However, high consumption of animal protein sources, especially red meat, results in an increased intake of saturated fat, cholesterol, iron, and salt, as well as an excessive acid load. Red meat intake may lead to an elevated production of uremic toxins by the gut microbiota, such as trimethylamine n-oxide (TMAO), indoxyl sulfate, and p-cresyl sulfate. These uremic toxins are associated with increased risk for cardiovascular (CV) mortality. Limiting the intake of red meat in patients with chronic kidney disease (CKD) thus may be a good strategy to reduce CV risk, and may slow the progression of kidney disease. In the present review, we discuss the role of red meat in the diet of patients with CKD. Additionally, we report on a pilot study that focused on the effect of a low-protein diet on TMAO plasma levels in nondialysis CKD patients.
Subject(s)
Red Meat/adverse effects , Red Meat/analysis , Renal Insufficiency, Chronic/diet therapy , Cardiovascular Diseases/etiology , Diet, Protein-Restricted , Dietary Fats/administration & dosage , Dietary Proteins/administration & dosage , Gastrointestinal Microbiome/physiology , Humans , Iron, Dietary/administration & dosage , Methylamines/blood , Methylamines/metabolism , Micronutrients/administration & dosage , Risk Factors , Toxins, Biological/metabolism , Vitamins/administration & dosage , Zinc/administration & dosageABSTRACT
Patients with chronic kidney disease (CKD) frequently have mineral and bone disorders (CKD-MBD) that are caused by several mechanisms. Recent research has suggested that uremic toxins from the gut such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS) could also be involved in the development of bone disease in patients with CKD. IS and PCS are produced by microbiota in the gut, carried into the plasma bound to serum albumin, and are normally excreted into the urine. However, in patients with CKD, there is an accumulation of high levels of these uremic toxins. The exact mechanisms of action of uremic toxins in bone disease remain unclear. The purpose of this brief review is to discuss the link between uremic toxins (IS and PCS) and bone mineral disease in chronic kidney disease.
