Plasma Retinol Concentration Is Mainly Driven by Transthyretin in Hemodialysis Patients

Abstract

Plasma retinol concentration is mainly driven by transthyretin in hemodialysis patients. Abstract BackgroundMicronutrients deficiencies in hemodialysis patients are due to low dietary intakes and intradialytic losses for hydrophilic micronutrients. Conversely, lipophilic non-dialyzable compounds might accumulate due to a lack of elimination through renal metabolism or dialysis. Other compounds have complex metabolism: their concentration is not explained by these phenomenons. Study design Monocentric observational longitudinal study Subjects hemodialysis patients Main outcome measurePlasma concentration of lipophilic micronutrients: retinol and its two cotransporters transthyretin and retinol binding protein 4, tocopherol, and carotenoids (α-and β-carotene, β-cryptoxanthin, lycopene, lutein, zeaxanthin) and all factors associated with one-year mortality ResultsWithin the 123 patients of the study, median age [IQR] was 77.5[69.5-84.5] years and 58.5% were male. Median retinol plasma concentration was 4.07 [2.65-5.51]µmol/L, and 91.9% of patient had high plasma retinol concentrations. In monovariate analysis, retinol levels were inversely correlated with mortality (HR=0. 57[0.45-0.72]; p<0.001). This effect remained significant after adjustment with several parameters. Nevertheless, the correlation between retinol and mortality disappeared as soon as transthyretin was added in the statistical model, suggesting an effect of transthyretin as confusing bias. Plasma retinol in hemodialysis patientsMedian tocopherol plasma concentration was 34.8[28.3-42.9]µmol/L and 72.4% of patients had high plasma tocopherol concentration. Neither tocopherol plasma levels, nor carotenoids concentrations were correlated with death in multivariate analysis. ConclusionsIn hemodialysis patients, the correlation between retinol plasma concentration and mortality represents the nutritional status but not a direct biological effect of retinol. Retinol is only a surrogate predictor of mortality. It might not represent vitamin A levels, but likely the transthyretin level. Plasma retinol levels should be interpreted cautiously in hemodialysis patients. Keywords Plasma retinol in hemodialysis patients IntroductionProtein energy wasting syndrome affects 30 to 60% of hemodialysis patients (HD) and contributes to high morbidity and mortality rates in this specific population [1]. Yet, in daily practices, very little concern is made about micronutrients (i.e. vitamins and trace elements) which are implicated in many metabolic functions including regulation of oxidative stress, or modulation of the immune system [2].Micronutrients deficiencies in HD patients are due to low dietary intakes, but also from intradialytic losses for small hydrophilic micronutrients, and conversely micronutrients accumulation, to a lack of elimination through renal metabolism or dialysis techniques for some lipophilic or non-dialyzable compounds [2,3]. Nevertheless, some compounds have more complex metabolism and their plasma concentration is not only explained by thes...

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