Associations Among Plant-Based Diet Quality, Uremic Toxins, and Gut Microbiota Profile in Adults Undergoing Hemodialysis Therapy.

OBJECTIVE: The objective of the study was to evaluate associations among diet quality, serum uremic toxin concentrations, and the gut microbiota profile in adults undergoing hemodialysis therapy. DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from a clinical trial involving adults receiving hemodialysis therapy. Usual dietary intake was determined using a diet history method administered by Accredited Practising Dietitians. Two approaches were used for diet quality assessment: (1) using three a priori defined plant-based diet indices-an overall plant-based diet index (PDI), a healthy PDI, and an unhealthy PDI and (2) classification of food group intake. Serum uremic toxins (p-cresyl sulfate and indoxyl sulfate (IS); free and total) were determined by ultra-performance liquid chromatography. Gut microbiota composition was established through sequencing the 16S rRNA gene in stool samples. RESULTS: Twenty-two adults (median age 70.5 [interquartile range: 59-76], 64% male) were included in the final analysis. Higher adherence to the PDI was associated with lower total IS levels (P = .028), independent of dialysis adequacy, urinary output, and blood albumin levels. In contrast, higher adherence to the unhealthy PDI was associated with increases in both free and total IS. Several other direct and inverse associations between diet quality with uremic toxins, microbial relative abundances, and diversity metrics were also highlighted. Diet-associated taxa showed significantly different trends of association with serum uremic toxin concentrations (P < .05). Higher adherence to the PDI was negatively associated with relative abundances of Haemophilus and Haemophilus parainfluenzae that were related to elevated total IS levels. In contrast, increased intake of food items considered unhealthy, such as animal fats, sweets and desserts, were associated with bacteria linked to higher IS and p-cresyl sulfate (total and free) concentrations. CONCLUSIONS: The quality of diet and food selections may influence uremic toxin production by the gut microbiota in adults receiving hemodialysis. Well-designed dietary intervention trials that adopt multi-omic technologies appropriate for the functional annotation of the gut microbiome are needed to validate our findings and establish causality.

Safety and Efficacy of Using Nuts to Improve Bowel Health in Hemodialysis Patients.

OBJECTIVE: Constipation is common in patients with end-stage kidney disease. Nondrug strategies to manage constipation are challenging because of dietary potassium, phosphate, and fluid restrictions. Nuts are a high-fiber food but are excluded from the diet because of the high potassium and phosphate content. The aim of this study was to examine the safety and efficacy of using nuts to improve constipation in adults undertaking hemodialysis (HD). DESIGN AND METHODS: Adult patients undertaking HD were recruited to this nonrandomized, 10-week repeated measures, within-subject, pragmatic clinical trial, conducted in two HD units. The intervention consisted of consumption of 40g of raw almonds daily for four weeks, followed by a two-week washout and four-week control period. The primary safety outcome measures were change in predialysis serum potassium and phosphate levels. The primary efficacy outcome was reduction in constipation, measured using the Bristol Stool Form Scale and Palliative Care Outcome Scale (POS-S) renal symptom score. Secondary outcomes included quality of life, selected uremic toxins, cognition, gut microbiota profile, and symptom burden. RESULTS: Twenty patients completed the trial (median age: 67 [interquartile range: 57.5-77.8] years, 51% male). After controlling for dialysis adequacy, anuria, dietary intake, bicarbonate, and parathyroid hormone, there were no statistically significant changes in serum potassium (P = 0.21) or phosphate (P = 0.16) associated with daily consumption of almonds. However, statistically significant improvements in constipation were seen at weeks 2, 3, 4, and 10. There were statistically significant improvements in quality of life (P = 0.030), overall symptom burden (P = 0.002), vomiting (P = 0.020), itching (P = 0.006), and skin changes (P = 0.002). CONCLUSION: Daily consumption of almonds for four weeks was safe, effective, and well tolerated. Improvements in quality of life and symptom burden warrant further research to elucidate potential mechanisms. The findings support the potential reinclusion of foods such as nuts into the diet of patients who underwent HD.

An efficient and robust MRI-guided radiotherapy planning approach for targeting abdominal organs and tumours in the mouse.

INTRODUCTION: Preclinical CT-guided radiotherapy platforms are increasingly used but the CT images are characterized by poor soft tissue contrast. The aim of this study was to develop a robust and accurate method of MRI-guided radiotherapy (MR-IGRT) delivery to abdominal targets in the mouse. METHODS: A multimodality cradle was developed for providing subject immobilisation and its performance was evaluated. Whilst CT was still used for dose calculations, target identification was based on MRI. Each step of the radiotherapy planning procedure was validated initially in vitro using BANG gel dosimeters. Subsequently, MR-IGRT of normal adrenal glands with a size-matched collimated beam was performed. Additionally, the SK-N-SH neuroblastoma xenograft model and the transgenic KPC model of pancreatic ductal adenocarcinoma were used to demonstrate the applicability of our methods for the accurate delivery of radiation to CT-invisible abdominal tumours. RESULTS: The BANG gel phantoms demonstrated a targeting efficiency error of 0.56 ± 0.18 mm. The in vivo stability tests of body motion during MR-IGRT and the associated cradle transfer showed that the residual body movements are within this MR-IGRT targeting error. Accurate MR-IGRT of the normal adrenal glands with a size-matched collimated beam was confirmed by γH2AX staining. Regression in tumour volume was observed almost immediately post MR-IGRT in the neuroblastoma model, further demonstrating accuracy of x-ray delivery. Finally, MR-IGRT in the KPC model facilitated precise contouring and comparison of different treatment plans and radiotherapy dose distributions not only to the intra-abdominal tumour but also to the organs at risk. CONCLUSION: This is, to our knowledge, the first study to demonstrate preclinical MR-IGRT in intra-abdominal organs. The proposed MR-IGRT method presents a state-of-the-art solution to enabling robust, accurate and efficient targeting of extracranial organs in the mouse and can operate with a sufficiently high throughput to allow fractionated treatments to be given.

Synthesis and characterization of polystyrene embolization particles doped with tantalum oxide nanoparticles for X-ray contrast.

Radiopaque and fluorescent embolic particles have been synthesized and characterised to match the size of vasculature found in tumours to ensure effective occlusion of the vessels. A literature search showed that the majority of vessels surrounding a tumour were less than 50 µm and therefore polydispersed polystyrene particles with a peak size of 50 µm have been synthesised. The embolic particles contain 5-8 nm amorphous tantalum oxide nanoparticles which provide X-ray contrast. Embolic particles containing up to 9.4 wt% tantalum oxide were prepared and showed significant contrast compared to the undoped polystyrene particles. The X-ray contrast of the embolic particles was shown to be linear (R(2) = 0.9) with respect to the concentration of incorporated tantalum nanoparticles. A model was developed which showed that seventy-five 50 µm embolic particles containing 10% tantalum oxide could provide the same contrast as 5 cm of bone. Therefore, the synthesized particles would provide sufficient X-ray contrast to enable visualisation within a tumour.