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Weekday sunlight exposure, but not vitamin D intake, influences the association between vitamin D receptor genotype and circulating concentration 25-hydroxyvitamin D in a pan-European population: the Food4Me study
Scope
Little is known about diet- and environment-gene interactions on 25-hydroxyvitamin D (25(OH)D concentration. This cross-sectional study aimed to investigate i) predictors of 25(OH)D concentration and relationships with vitamin D genotypes and ii) whether dietary vitamin D intake and sunlight exposure modified these relationships.
Methods and results
Participants from the Food4Me study (n = 1312; age 18–79) were genotyped for vitamin D receptor (VDR) and vitamin D binding protein at baseline and a genetic risk score was calculated. Dried blood spot samples were assayed for 25(OH)D concentration and dietary and lifestyle information collected. Circulating 25(OH)D concentration was lower with increasing genetic risk score, lower in females than males, higher in supplement users than non-users and higher in summer than winter. Carriage of the minor VDR allele was associated with lower 25(OH)D concentration in participants with the least sunlight exposure. Vitamin D genotype did not influence the relationship between vitamin D intake and 25(OH)D concentration.
Conclusion
Age, sex, dietary vitamin D intake, country, sunlight exposure, season and vitamin D genetic risk score were associated with circulating 25(OH)D concentration in a pan-European population. The relationship between VDR genotype and 25(OH)D concentration may be influenced by weekday sunlight exposure but not dietary vitamin D intake
Endotoxaemia in Haemodialysis: A Novel Factor in Erythropoetin Resistance?
Background/Objectives
Translocated endotoxin derived from intestinal bacteria is a driver of systemic inflammation and oxidative stress. Severe endotoxaemia is an underappreciated, but characteristic finding in haemodialysis (HD) patients, and appears to be driven by acute repetitive dialysis induced circulatory stress. Resistance to erythropoietin (EPO) has been identified as a predictor of mortality risk, and associated with inflammation and malnutrition. This study aims to explore the potential link between previously unrecognised endotoxaemia and EPO Resistance Index (ERI) in HD patients.
Methodology/Principal Findings
50 established HD patients were studied at a routine dialysis session. Data collection included weight, BMI, ultrafiltration volume, weekly EPO dose, and blood sampling pre and post HD. ERI was calculated as ratio of total weekly EPO dose to body weight (U/kg) to haemoglobin level (g/dL). Mean haemoglobin (Hb) was 11.3±1.3 g/dL with a median EPO dose of 10,000 [IQR 7,500–20,000] u/wk and ERI of 13.7 [IQR 6.9–23.3] ((U/Kg)/(g/dL)). Mean pre-HD serum ET levels were significantly elevated at 0.69±0.30 EU/ml. Natural logarithm (Ln) of ERI correlated to predialysis ET levels (r = 0.324, p = 0.03) with a trend towards association with hsCRP (r = 0.280, p = 0.07). Ln ERI correlated with ultrafiltration volume, a driver of circulatory stress (r = 0.295, p = 0.046), previously identified to be associated with increased intradialytic endotoxin translocation. Both serum ET and ultrafiltration volume corrected for body weight were independently associated with Ln ERI in multivariable analysis.
Conclusions
This study suggests that endotoxaemia is a significant factor in setting levels of EPO requirement. It raises the possibility that elevated EPO doses may in part merely be identifying patients subjected to significant circulatory stress and suffering the myriad of negative biological consequences arising from sustained systemic exposure to endotoxin
Cognitive changes associated with switching to frequent nocturnal hemodialysis or renal transplantation
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