Modulation of miR-29a and miR-29b Expression and Their Target Genes Related to Inflammation and Renal Fibrosis by an Oral Nutritional Supplement with Probiotics in Malnourished Hemodialysis Patients.

Malnutrition is prevalent in patients with chronic kidney disease (CKD), especially those on hemodialysis. Recently, our group described that a new oral nutritional supplement (ONS), specifically designed for malnourished (or at risk) hemodialysis patients with a "similar to the Mediterranean diet" pattern, improved caloric-protein intake, nutritional status and biomarkers of inflammation and oxidation. Our aim in this study was to evaluate whether the new ONS, associated with probiotics or not, may produce changes in miRNA's expression and its target genes in malnourished hemodialysis patients, compared to individualized diet recommendations. We performed a randomized, multicenter, parallel-group trial in malnourished hemodialysis patients with three groups (1: control (C) individualized diet (n = 11); 2: oral nutritional supplement (ONS) + placebo (ONS-PL) (n = 10); and 3: ONS + probiotics (ONS-PR) (n = 10)); the trial was open regarding the intake of ONS or individualized diet recommendations but double-blinded for the intake of probiotics. MiRNAs and gene expression levels were analyzed by RT-qPCR at baseline and after 3 and 6 months. We observed that the expression of miR-29a and miR-29b increased significantly in patients with ONS-PR at 3 months in comparison with baseline, stabilizing at the sixth month. Moreover, we observed differences between studied groups, where miR-29b expression levels were elevated in patients receiving ONS-PR compared to the control group in the third month. Regarding the gene expression levels, we observed a decrease in the ONS-PR group compared to the control group in the third month for RUNX2 and TNFα. TGFB1 expression was decreased in the ONS-PR group compared to baseline in the third month. PTEN gene expression was significantly elevated in the ONS-PR group at 3 months in comparison with baseline. LEPTIN expression was significantly increased in the ONS-PL group at the 3-month intervention compared to baseline. The new oral nutritional supplement associated with probiotics increases the expression levels of miR-29a and miR-29b after 3 months of intervention, modifying the expression of target genes with anti-inflammatory and anti-fibrotic actions. This study highlights the potential benefit of this oral nutritional supplement, especially associated with probiotics, in malnourished patients with chronic renal disease on hemodialysis.

Effect on nutritional status and biomarkers of inflammation and oxidation of an oral nutritional supplement (with or without probiotics) in malnourished hemodialysis patients. A multicenter randomized clinical trial "Renacare Trial".

Background: Malnutrition in patients undergoing hemodialysis is frequent and associated with a reduction in muscular mass and strength, with an increment in biomarkers of inflammation and oxidation. Materials and methods: Randomized, multicenter, parallel-group trial in malnourished hemodialysis patients with three groups [(1) control (C) individualized diet, (2) oral nutritional supplement-ONS- + placebo-SU- PL-, and (3) ONS + probiotics-SU-PR]; the trial was open regarding the intake of ONS or individualized diet recommendations, but double-blind for the intake of probiotics. We obtained, at baseline and after 3 and 6 months, anthropometric measurements, handgrip strength, bioelectrical impedance analysis (BIA), dietary records, and routine biochemical parameters. Inflammation and oxidation were determined using ELISA techniques (Versamax and ProcartaPlex multiplex Immunoassay). Results were analyzed by intention to treat. Results: A total of 31 patients (11 corresponding to group C, 10 to SU-PL, and 10 to SU-PR) completed the 6-months trial. The two groups that took supplements significantly increased their protein calorie, fat (total and n-3), and fiber intake. Weight and fat-free mass (FFM) also increased significantly in the groups on supplements, both at 3 and 6 months, and dynamometry did so in the SU-PL group. At month 3, prealbumin and vitamin D were significantly increased in the SU-TOT (SU-PL + SU-PR) group. No changes were observed regarding levels of phosphorus and potassium in any of the groups. Urea increased significantly at 6 months in the SU-PL group. There were significant changes in some inflammation biomarkers in the groups on supplements during the intervention (brain-derived neurotrophic factor, bone morphogenetic protein-2, MCP-1, IL-1-beta, IL-10, IL-4, and IL-8). The total antioxidant capacity (TAC) increased significantly in the supplemented patients, with no significant changes observed in isoprostanes. Conclusion: The specific ONS improved protein-calorie intake, nutritional status (mainly FFM), and some biomarkers of inflammation/oxidation. The addition of probiotics could have a synergistic effect with ONS in such biomarkers. Clinical trail registration: https://clinicaltrials.gov/ct2/show/, identifier NCT03924089.

Differences in Malnutrition Inflammation Score of Hemodialysis Patients Associated With Hemodialysis Factors. A Spanish Multicenter Epidemiologic Study.

OBJECTIVES: The aims of this study are to analyze the prevalence of malnutrition in hemodialysis (HD) patients in Spain, and to assess the association of malnutrition in these patients with sociodemographic characteristics, comorbidity, and parameters related to HD. DESIGN AND METHODS: A multicenter, retrospective, cross-sectional study in HD patients from centers all over Spain was conducted. Nutritional status of patients was assessed using Malnutrition Inflammation Score (MIS), and was stratified according to MIS values into 5 categories: ≤2, normal nutrition; >2 to ≤5, mild malnutrition or risk of malnutrition; >5 to ≤7, moderate malnutrition; >7 to ≤10, severe malnutrition, and >10, extreme malnutrition. RESULTS: A total of 52 Spanish HD Units participated in the study enrolling 2,748 patients. Mean age of patients was 68.20 ± 14.24 years, 1,811 (65.9%) were men. Mean time on HD was 55.63 ± 63.25 months. Using an MIS cut-off point of 2 for malnutrition, 89% of patients were malnourished (MIS > 2). However, with a cut-off point of 5, more commonly described in the literature, the percentage of patients with malnutrition was reduced to 51.7%. Using this cut-off, we observed significant differences between patients with malnutrition and normo-nourished patients in biochemical parameters, age, Charlson Index, HD residual renal function, scheme, and vascular access (permanent catheter vs arteriovenous fistula). A multivariate regression analysis showed that age, sex, HD scheme, vascular access, residual renal function, and comorbidity index were predictive factors for malnutrition. We found that a high percentage of HD patients with malnutrition did not receive oral supplementation. CONCLUSIONS: The prevalence of malnutrition in HD patients in Spain, assessed using the MIS scale, was high. Higher malnutrition was associated with the use of catheter versus fistula, and standard HD versus online hemodiafiltration, and with the absence of residual renal function, older age, greater comorbidity, and male sex. Malnourished patients had a low rate of oral supplementation.

Impact of the Nutrition-Inflammation Status on the Functionality of Patients with Chronic Kidney Disease.

Functional capacity of chronic kidney disease (CKD) patients is compromised by their nutrition-inflammation status. We evaluated the functional capacity of advanced chronic kidney disease (ACKD) patients and the influence of the nutrition-inflammation status. In a cross-sectional study, which included ACKD patients from the nephrology department of the Hospital Universitario de la Princesa in Madrid, Spain, we assessed: functional capacity with the Short Physical Performance Battery (SPPB) test, interpreting a result <7 in the test as low functionality; body composition with monofrequency bioimpedance; muscular strength with hand grip strength; nutritional and inflammatory status using biochemical parameters and the Malnutrition Inflammation Scale (MIS). A total of 255 patients with ACKD were evaluated, 65.8% were men, their mean age was 70.65 ± 11.97 years and 70.2% of the patients had an age >65 years. The mean score of SPPB was 8.50 ± 2.81 and 76.4% of the patients presented a score ≥7, with a higher percentage in the group of men. The percentage of patients with limitations increased with age. The patients with SPPB values higher than 7 showed high values of albumin and low soluble C-reactive protein (s-CRP) and MIS. We found better functionality in well-nourished patients. A multivariate logistic regression model established an association of high albumin values with a better functional capacity (OR: 0.245 CI: 0.084−0.714 p < 0.010), while another model showed an association between CRP values and decreased functionality (OR: 1.267 CI: 1.007−1.594 p = 0.044). Conclusion: nutritional status and body composition influence on the functional capacity of patients with ACKD.

Nutritional Predictors of Mortality after 10 Years of Follow-Up in Patients with Chronic Kidney Disease at a Multidisciplinary Unit of Advanced Chronic Kidney Disease.

Nutritional monitoring in advanced chronic kidney disease (ACKD) units provides personalized care and improves clinical outcomes. This study aimed to identify mortality risk factors in chronic kidney disease (CKD) patients on nutritional follow-up in the multidisciplinary ACKD unit. A retrospective cross-sectional observational study was conducted in 307 CKD patients' stage 3b, 4−5 followed-up for 10 years. Clinical and nutritional monitoring was performed by malnutrition-inflammation score (MIS), biochemical parameters (s-albumin, s-prealbumin, and serum C-reactive protein (s-CRP), body composition measured by bioelectrical impedance analysis (BIA), anthropometry, and handgrip strength measurements. The sample was classified into non-survivors, survivors, and censored groups. Of the 307 CKD patients, the prevalence of protein-energy wasting (PEW) was 27.0% using MIS > 5 points, s-CRP > 1 mg/dL was 19.20%, and 27.18% died. Survivors had higher significant body cell mass (BCM%) and phase angle (PA). Survival analyses significantly showed that age > 72 years, MIS > 5 points, s-prealbumin ≤ 30 mg/dL, PA ≤ 4°, and gender-adjusted handgrip strength (HGS) were associated with an increased risk of mortality. By univariate and multivariate Cox regression, time on follow-up (HR:0.97), s-prealbumin (HR:0.94), and right handgrip strength (HR:0.96) were independent predictors of mortality risk at 10 years of follow-up in the ACKD unit. Nutritional monitoring in patients with stage 3b, 4−5 CKD helps to identify and treat nutritional risk early and improve adverse mortality prognosis.

¿Es útil el SPPB como método de screening de capacidad funcional en pacientes con enfermedad renal crónica avanzada? / Is SPPB useful as a screening method of functional capacity in patients with advanced chronic kidney disease?

INTRODUCCIÓN Y OBJETIVO: Una de las consecuencias de la ERC, es el deterioro de la capacidad funcional, pudiéndose manifestar desde distintos estadios de la enfermedad, hasta el tratamiento renal sustitutivo. El objetivo de este estudio fue determinar la funcionalidad de los pacientes con ERCA, mediante test de capacidad funcional, valorando de forma paralela la utilidad del SPPB como test de cribado. Materiales y métodos: Se evaluó la capacidad funcional de pacientes ERCA, utilizando los test SPPB, 6MM, TUTG y STS. También se determinó la fuerza muscular con dinamometría manual. Resultados: De 121 pacientes que acudieron a la consulta ERCA, 118 presentaron una mínima funcionalidad para poder realizar pruebas de capacidad funcional, un 71,2% de los pacientes fueron capaces de realizar los 4 test, un 28,8% solo pudo realizar el test SPPB. A un 71,43% de pacientes que presentaron una puntuación baja en SPPB, no se les pudo seguir evaluando con el resto de test, mientras que el 92,31% de los que presentaron una puntuación alta, continuaron con el resto de pruebas. Al diferenciar por rangos de edad, la mayoría de los pacientes jóvenes presentaban mínimas limitaciones, encontrando tasas más altas de discapacidad en rangos de edad mayores. Una buena puntuación en SPPB supuso presentar buena capacidad funcional y permitió seguir evaluando al paciente, obteniendo mejores resultados con el resto de test y más fuerza muscular. Una buena composición corporal y mejor estado nutricional supuso una mejor funcionalidad. Conclusión: A falta de un consenso de cuál es el mejor método de determinar la capacidad funcional del paciente renal, y para poder evaluar a todos los pacientes, proponemos utilizar el test SPPB como método de screening, y en función del resultado utilizar el resto de los test para realizar estudio más completo si es necesario

INTRODUCTION AND OBJECTIVE: One of the consequences of the CKD, is the deterioration of the functional capacity, being able to manifest from different stages of the disease, until renal replacement therapy. The objective of this study was to determine the functionality of patients with CKD through functional capacity test, valuing the usefulness of the SPPB as a screening test in parallel. Materials and methods: It assessed the functional capacity of patients with CKD, using the test SPPB, 6MM, TUTG and STS. Also found the muscle strength with manual dynamometry. RESULTS: Of 121 patients who came to the CKD query, 118 presented a minimum functionality to perform tests of functional capacity, a 71.2% of the patients were able to perform 4 tests, a 28.8% only could make the SPPB test. To a 71.43% of patients who presented a low score in SPPB, not could follow assessed them with the rest of the test, while the 92.31% of which had a high score, continued with the rest of the evidence. To differentiate by age ranges, the majority of young patients have minimal limitations, finding higher rates of disability in older age ranges. A good score in SPPB meant to present good functional capacity and allowed to continue evaluating the patient, obtaining better results with the rest of test and more muscle strength. A good nutritional better status and body composition was a better functionality. CONCLUSION: In the absence of a consensus of what is the best method of determining the functional capacity of the kidney patient, and to assess all patients, propose to use the test SPPB as screening method, and depending on the result used as the rest of the test to more complete if it is necessary to study

Is SPPB useful as a screening method of functional capacity in patients with advanced chronic kidney disease? / ¿Es útil el SPPB como método de screening de capacidad funcional en pacientes con enfermedad renal crónica avanzada?

INTRODUCTION AND OBJECTIVE: One of the consequences of the CKD, is the deterioration of the functional capacity, being able to manifest from different stages of the disease, until renal replacement therapy. The objective of this study was to determine the functionality of patients with CKD through functional capacity test, valuing the usefulness of the SPPB as a screening test in parallel. MATERIALS AND METHODS: It assessed the functional capacity of patients with CKD, using the test SPPB, 6MM, TUTG and STS. Also found the muscle strength with manual dynamometry. RESULTS: Of 121 patients who came to the CKD query, 118 presented a minimum functionality to perform tests of functional capacity, a 71.2% of the patients were able to perform 4 tests, a 28.8% only could make the SPPB test. To a 71.43% of patients who presented a low score in SPPB, not could follow assessed them with the rest of the test, while the 92.31% of which had a high score, continued with the rest of the evidence. To differentiate by age ranges, the majority of young patients have minimal limitations, finding higher rates of disability in older age ranges. A good score in SPPB meant to present good functional capacity and allowed to continue evaluating the patient, obtaining better results with the rest of test and more muscle strength. A good nutritional better status and body composition was a better functionality. CONCLUSION: In the absence of a consensus of what is the best method of determining the functional capacity of the kidney patient, and to assess all patients, propose to use the test SPPB as screening method, and depending on the result used as the rest of the test to more complete if it is necessary to study.

Influence of dietary protein intake on body composition in chronic kidney disease patients in stages 3-5: A cross-sectional study / Influencia del consumo de proteínas en la composición corporal de pacientes con enfermedad renal crónica en estadios 3-5: estudio transversal

INTRODUCTION: A controlled protein intake has shown beneficial effects to preserve renal function and nutritional status in chronic kidney disease (CKD) patients. This study aimed to analyze usual dietary protein intake and its potential contribution to body composition in CKD patients in stages 3-5. METHOD: Cross-sectional study in 134 CKD patients in stages 3-5 (mean e-GFR: 19.4 ± 8.7 ml/min/1.73 m2; males 68.7% and primary CKD etiology was diabetes mellitus, 35.8%). Demographic, clinical and nutritional parameters were evaluated. Normalized protein nitrogen appearance (nPNA), was used as a surrogate marker of dietary protein intake. The sample was classified into three nPNA groups (Gn): G1: < 0.8g/kg/day; G2: 0.8-1g/kg/day and, G3: ≥ 1g/kg/day. Assessment of nutritional status using the malnutrition-inflammation score (MIS), anthropometric measures and laboratory parameters. Analysis of body composition and hydration status by bioelectrical impedance analysis (BIVA-101-RJL system). Statistical analysis by SPSS V.20. RESULTS: Overall mean nPNA values were 0.91 ± 0.23 g of protein/kg BW/day and only 32.1% had a dietary protein intake < 0.8g of protein/kg BW/day. Most of the CKD patients (65.5%) were in stages 4 or 5. Prevalence of protein-energy-wasting (PEW) syndrome measured by MIS was 15%. By analyzing differences between nPNA groups, body weight (BW), BMI and triceps-skinfold (TSF) thickness were significantly higher in the group with nPNA ≥ 1g/kg BW/day (G3), whereas a significant inverse relationship was found with the percentages of body cell mass (BCM%), fat-free mass (FFM%), muscle mass (MM%) and phase angle (PA) in the group with the lowest nPNA (G1). Analysis of gender among subjects showed significant differences with BW, FFM%, TSF and mid-arm muscle circumference (MAMC%). Linear regression analysis showed that resistance, BCM%, MM%, and serum albumin were significant predictors of nPNA as a surrogate marker of daily protein intake (R = 0.51; R2 = 0.29; R2 adjusted = 0.23; p < 0.001). CONCLUSION: Controlled protein intake is one of the cornerstones of treatment in CKD patients. A low protein intake in patients with CKD stages 3 and 4-5 was associated with loss of muscle mass in the advanced-CKD unit. The loss of muscle mass appears as an early indicator of nutritional comprised. Factors such, elderly age and loss of eGFR, showed lower protein intake and were associated with muscle loss, especially in women. Further longitudinal studies are required to evaluate the contribution of different protein intakes to uremic symptoms, nutritional status, body composition and CKD progression

INTRODUCCIÓN: El control de la ingesta proteica ha mostrado efectos beneficiosos preservando la función renal y el estado nutricional en pacientes con enfermedad renal crónica (ERC). El objetivo del estudio fue analizar la ingesta habitual de proteína, y su potencial contribución en la composición corporal en los pacientes con ERC estadios 3-5. MÉTODO: Estudio observacional transversal en 134 pacientes con ERC estadios 3-5 (media e-TFG: 19,4 ± 8,7ml/min/1,73 m2; varones: 68,7% y etiología primaria de la ERC, diabetes mellitus: 35,8%). Se evaluaron parámetros demográficos, clínicos y nutricionales. La aparición de nitrógeno proteico normalizado (nPNA) se utilizó como marcador sustituto de la ingesta proteica. La muestra fue clasificada según el nPNA en 3 grupos (Gn): G1: < 0,8g/kg/día; G2: 0,8-1g/kg/día y G3: ≥ 1g/kg/día. Valoración nutricional por la escala de malnutrición-inflamación (MIS), medidas antropométricas y parámetros de laboratorio. Análisis de composición corporal y del patrón de hidratación mediante bioimpedancia eléctrica (BIVA-101®, RJL System). Análisis estadístico por SPSS(R) V.20. RESULTADOS: Globalmente los valores medios de nPNA fueron 0,91 ± 0,23g proteína/kg peso corporal/día, y tan solo el 32,1% tenían una ingesta proteica < 0,8 g de proteína/kg peso corporal/día. El 65,5% de los pacientes con ERC estaban en estadios 4 y 5. La prevalencia de síndrome de desgaste proteico-energético (SDP) medido por MIS era del 15%. Analizando las diferencias con el nPNA entre los grupos, el peso corporal, el índice de masa corporal y el pliegue tricipital (PCT), eran significativamente mayores en el grupo con nPNA≥1g/kg peso corporal/día (G3), mientras que se encontró relación inversa significativa con los porcentajes de la masa celular (MC%), de la masa magra (MMagra%), de la masa muscular (MM%) y del ángulo de fase (AF) en el grupo con menor nPNA (G1). El análisis del género entre los sujetos mostró diferencias significativas con el peso corporal, MMagra%, PCT y la circunferencia muscular del brazo (CMB%). El análisis de regresión lineal demostró que la resistencia MC%, MM% y la albúmina sérica eran predictores significativos del nPNA como marcador de la ingesta proteica habitual (R = 0,51; R2 = 0,29; R2 ajustado = 0,23; p < 0,001). CONCLUSIÓN: El control de la ingesta proteica es uno de los pilares del tratamiento en los pacientes con ERC. La dieta hipoproteica en pacientes con ERC estadios 3-5 se asoció con una pérdida de la masa muscular en la unidad de ERC avanzada. La pérdida de masa muscular aparece como un indicador temprano de compromiso nutricional. La edad avanzada y la pérdida de TFG-e se asociaron con menor ingesta proteica y pérdida de masa muscular asociada, especialmente en mujeres. Nuevos estudios longitudinales, son necesarios para evaluar la contribución de la ingesta de proteínas en los síntomas urémicos, el estado nutricional, la composición corporal y la progresión de la ERC

Influence of dietary protein intake on body composition in chronic kidney disease patients in stages 3-5: A cross-sectional study.

INTRODUCTION: A controlled protein intake has shown beneficial effects to preserve renal function and nutritional status in chronic kidney disease (CKD) patients. This study aimed to analyze usual dietary protein intake and its potential contribution to body composition in CKD patients in stages 3-5. METHOD: Cross-sectional study in 134 CKD patients in stages 3-5 (mean e-GFR: 19.4±8.7ml/min/1.73m2; males 68.7% and primary CKD etiology was diabetes mellitus, 35.8%). Demographic, clinical and nutritional parameters were evaluated. Normalized protein nitrogen appearance (nPNA), was used as a surrogate marker of dietary protein intake. The sample was classified into three nPNA groups (Gn): G1: <0.8g/kg/day; G2: 0.8-1g/kg/day and, G3: ≥1g/kg/day. Assessment of nutritional status using the malnutrition-inflammation score (MIS), anthropometric measures and laboratory parameters. Analysis of body composition and hydration status by bioelectrical impedance analysis (BIVA-101-RJL system). Statistical analysis by SPSS v.20. RESULTS: Overall mean nPNA values were 0.91±0.23g of protein/kg BW/day and only 32.1% had a dietary protein intake <0.8g of protein/kg BW/day. Most of the CKD patients (65.5%) were in stages 4 or 5. Prevalence of protein-energy-wasting (PEW) syndrome measured by MIS was 15%. By analyzing differences between nPNA groups, body weight (BW), BMI and triceps-skinfold (TSF) thickness were significantly higher in the group with nPNA ≥1g/kg BW/day (G3), whereas a significant inverse relationship was found with the percentages of body cell mass (BCM%), fat-free mass (FFM%), muscle mass (MM%) and phase angle (PA) in the group with the lowest nPNA (G1). Analysis of gender among subjects showed significant differences with BW, FFM%, TSF and mid-arm muscle circumference (MAMC%). Linear regression analysis showed that resistance, BCM%, MM%, and serum albumin were significant predictors of nPNA as a surrogate marker of daily protein intake (R=0.51; R2=0.29; R2 adjusted=0.23; p<0.001). CONCLUSION: Controlled protein intake is one of the cornerstones of treatment in CKD patients. A low protein intake in patients with CKD stages 3 and 4-5 was associated with loss of muscle mass in the advanced-CKD unit. The loss of muscle mass appears as an early indicator of nutritional comprised. Factors such, elderly age and loss of eGFR, showed lower protein intake and were associated with muscle loss, especially in women. Further longitudinal studies are required to evaluate the contribution of different protein intakes to uremic symptoms, nutritional status, body composition and CKD progression.