Low-protein diet supplemented with inulin lowers protein-bound toxin levels in patients with stage 3b-5 chronic kidney disease: a randomized controlled study / La dieta baja en proteínas suplementada con inulina reduce los niveles de toxinas unidas a proteínas en pacientes con enfermedad renal crónica en estadio 3b-5: un estudio controlado aleatorio

Objective: this study aimed to evaluate whether low-salt low-protein diet (LPD) supplemented with 10 g of inulin could lower serum toxin levels in patients with chronic kidney disease (CKD), thereby providing evidence for adjusting dietary prescriptions of inhospital patients and outpatient nutrition consultants. Methods: we randomized 54 patients with CKD into two groups. Dietary protein intake compliance was evaluated using a 3-day dietary diary and 24-h urine nitrogen levels. The primary outcomes were indoxyl sulfate (IS) and p-cresyl sulfate (PCS), and secondary outcomes included inflammation marker levels, nutritional status, and renal function. We assessed 89 patients for eligibility, and a total of 45 patients completed the study, including 23 and 22 in the inulin-added and control groups, respectively. Results: PCS values decreased in both groups after intervention: inulin-added group, ∆PCS -1.33 (-4.88, -0.63) μg/mL vs. LPD group, -4.7 (-3.78, 3.69) μg/mL (p = 0.058). PCS values reduced from 7.52 to 4.02 μg/mL (p < 0.001) in the inulin-added group (p < 0.001). Moreover, IS decreased from 3.42 (2.53, 6.01) μg/mL to 2.83 (1.67, 4.74) μg/mL after adding inulin; ∆IS was -0.64 (-1.48, 0.00) μg/mL, and a significant difference was observed compared with the control group (p = 0.004). The inflammation index decreased after intervention. Conclusion: dietary fiber supplementation may reduce serum IS and PCS levels and modulate their inflammatory status in predialysis CKD patients.(AU)

Objetivo: este ensayo aleatorizado doble ciego comparó el efecto de una dieta baja en proteínas (LPD) con o sin suplementos orales de 10 gde inulina en los niveles de PBUT en pacientes con ERC en prediálisis durante 12 semanas.Métodos: clasificamos aleatoriamente a 54 pacientes con ERC en dos grupos. El cumplimiento de la ingesta dietética de proteínas se evaluóutilizando un diario dietético de 3 días y nitrógeno en orina de 24 horas. Los resultados primarios fueron IS y PCS y los resultados secundariosincluyeron niveles de marcadores de inflamación, estado nutricional y función renal. Evaluamos la elegibilidad de 89 pacientes y 45 completaronla intervención, incluidos 23 y 22 en los grupos de inulina añadida y de control, respectivamente.Resultados: el sodio urinario promedio de 24 horas fue de 86 mmol/día y la ingesta promedio de proteínas fue de ~0,7 g/kg/día. Los valores dePCS exhibieron una tendencia decreciente en ambos grupos después de la intervención: grupo con inulina añadida, ∆PCS -1.33 (-4.88, -0.63)μg/mL vs. grupo LPD, -4.7 (-3.78, 3.69) μg/mL) (p =0,058). Los valores de PCS se redujeron de 7,52 a 4,02 μg/mL (p < 0,001) con inulina(p < 0,001). Además, IS disminuyó de 3,42 (2,53, 6,01) μg/mL a 2,83 (1,67, 4,74) μg/mL después de agregar inulina; El ∆IS fue -0,64 (-1,48;0,00) μg/mL y se observó una diferencia significativa en comparación con el grupo control (p =0,004).Conclusión: la suplementación con fibra dietética puede reducir las toxinas de unión a proteínas séricas en pacientes con ERC en prediálisisy modular su estado inflamatorio.(AU)

Hemocompatible hemoadsorbent for effective removal of protein-bound toxin in serum.

Resin hemoperfusion is a life-saving treatment for drug intoxication or hepatic failure of patients. However, current resin adsorbents exhibit a limited hemocompatibility or low adsorption efficiency, representing a major roadblock to successful clinical applications. In this work, we developed a hemocompatible and effective hemoadsorbent based on polystyrene resin (H103) microparticles encapsulated in anti-biofouling zwitterionic poly(carboxybetaine) (PCB) hydrogels. Apart from a strong mechanical stability, this PCB-based adsorbent (PCB-H103) exhibited excellent hemocompatibility (hemolysis ratio was ∼0.64%), which was attributed to the anti-biofouling property of PCB hydrogel. In addition, it can efficiently adsorb both small and middle molecular weight molecules in phosphate-buffered saline, and the efficiencies were significantly higher than poly(ethylene glycol) methacrylate-based and poly(2-hydroxyethyl methacrylate)-based adsorbent counterparts, indicating the favorable permeability of PCB hydrogel coating. More importantly, PCB-H103 could effectively remove protein-bound toxins including phenol red and bilirubin in bovine serum albumin solution or even in 100% fetal bovine serum (FBS). In 100% FBS, the adsorption capacity of PCB-H103 towards bilirubin was 8.3 times higher than that of pristine clinical-scale resin beads. Findings in this work may provide a new strategy for the development of modern resin hemoperfusion technology.

A new method to increase the adsorption of protein-bound toxins in artificial liver support systems.

In this work, a new method, called the preconcentration method (PCM), is proposed to increase the adsorption of protein-bound toxins onto adsorbents in artificial liver support systems. In the PCM, a concentrator is installed before the inlet of the adsorbent cartridge. This method is validated in an experiment using activated carbon to remove albumin-bound bilirubin, and the mechanism of the increase in adsorption is theoretically explained with breakthrough curve and equilibrium adsorption analyses. Our results show that when this PCM is used, the mass transfer rate of bilirubin from solution to activated carbon is enhanced, the adsorbed bilirubin amount per unit mass of activated carbon is greatly increased, and more albumin-bound bilirubin molecules are quickly removed from the albumin solution. When the concentration ratio (the ratio of the inlet flow rate to the outflow rate of the concentrator) is 2.59, the adsorption efficiency of activated carbon at 120 min is increased by approximately 36%. Only approximately 60 min is required for the bilirubin concentration to decrease from 19.3 to 13.0 mg/dL; however, without the PCM, nearly 180 min is needed. In addition, by adjusting the concentration ratio, the adsorption of albumin-bound bilirubin onto activated carbon can be further increased.