Calcium isotopes as a biomarker for vascular calcification in chronic kidney disease.

Calcium balance is abnormal in adults with chronic kidney disease (CKD) and is associated with the development of vascular calcification. It is currently not routine to screen for vascular calcification in CKD patients. In this cross-sectional study, we investigate whether the ratio of naturally occurring calcium (Ca) isotopes, 44Ca and 42Ca, in serum could be used as a noninvasive marker of vascular calcification in CKD. We recruited 78 participants from a tertiary hospital renal center: 28 controls, 9 subjects with mild-moderate CKD, 22 undertaking dialysis and 19 who received a kidney transplant. For each participant, systolic blood pressure, ankle brachial index, pulse wave velocity, and estimated glomerular filtration rate were measured, along with serum markers. Calcium concentrations and isotope ratios were measured in urine and serum. While we found no significant association between urine Ca isotope composition (noted δ44/42Ca) between the different groups, δ44/42Ca values in serum were significantly different between healthy controls, subjects with mild-moderate CKD and those undertaking dialysis (P < 0.01). Receiver operative characteristic curve analysis shows that the diagnostic utility of serum δ44/42Ca for detecting medial artery calcification is very good (AUC = 0.818, sensitivity 81.8% and specificity 77.3%, P < 0.01), and performs better than existing biomarkers. Although our results will need to be verified in prospective studies across different institutions, serum δ44/42Ca has the potential to be used as an early screening test for vascular calcification.

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.