Dietary Intake of Proteins and Calories Is Inversely Associated With The Oxidation State of Plasma Thiols in End-Stage Renal Disease Patients

Abstract

Objectives: Oxidative stress contributes to the pathogenesis of protein-energy wasting in maintenance hemodialysis (MHD) patients, but knowledge of specific effectors and mechanisms remains fragmented. Aim of the study was to define whether and how food intake is involved in the causal relationship between oxidative stress and protein-energy wasting.

Methods: Seventy-one adult MHD patients and 24 healthy subjects (control) were studied cross-sectionally with analyses of diet record and of oxidative stress, as measured by a battery of plasma thiols including the protein sulfhydryl (-SH) group (PSH) levels (a marker of total protein-SH reducing capacity), the protein thiolation index (PTI, the ratio between disulfide, i.e., oxidized and reduced -SH groups in proteins), low molecular mass (LMM) thiols, LMM disulfides, and mixed LMM-protein disulfides. In addition, interleukin-6 (IL-6), albumin, C-reactive protein, and neutrophil gelatinase-associated lipocalin (NGAL) were measured as markers of inflammation.

Results: The patients showed low energy (22.0 ± 8.4 kcal/kg/day) and adequate protein (1.0 ± 0.4 g/kg/day) intakes, high levels of cystine (CySS; patients vs.

Control: 113.5 [90.9-132.8] vs. 68.2 [56.2-75.7] μM), cysteinylated proteins (CySSP; 216.0 [182.8-254.0] vs. 163.5 [150.0-195.5] μM), and high PTI (0.76 [0.61-0.88] vs. 0.43 [0.40-0.54]; P < .001 in all comparisons). In patients, variation of CySSP was explained by a standard regression model (R = 0.775; P = .00001) that included significant contributions of protein intake (β = -0.361), NGAL (β = 0.387), age (β = 0.295), and albumin (β = 0.457). In the same model, variation of PTI (R = 0.624; P = .01) was explained by protein intake (β = -0.384) and age (β = 0.326) and NGAL (β = 0.311). However, when PSH was entered as dependent variable (R = 0.730; P = .0001), only serum albumin (β = 0.495) and age (β = -0.280), but not dietary intake or NGAL, contributed to the model.

Conclusions: In MHD, markers of thiol oxidation including CySSP and PTI show independent association with dietary intake and NGAL, whereas PSH, a marker of thiol-reducing capacity, did not associate with these same variables. The mechanism(s) responsible for inverse association between oxidative stress and food intake in MHD remain undefined.

Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Plasma levels (median [IQR]) of reduced and disulfide fractions of cysteine in 24 healthy subjects (C) and 71 hemodialysis (MHD) patients. Panel A: cysteine (Cys);Panel B: cystine (CySS); Panel C: mixed cystine-protein disulfide (CySSP). Statistical comparison of C and MHD for each cysteine fraction with the Mann-Whitney U; Φ indicates p<0.001.

Figure 2

Plasma levels (median [IQR]) of (A) protein sulfhydryl groups (PSH) and (B) protein thiolation index (PTI) in 24 healthy subjects (C) and 71 hemodialysis (MHD) patients. Statistical comparison of C and MHD for each parameter with the Mann-Whitney U; Φ indicates p<0.001.

Figure 3

Partial correlation plots from the standard model multiple regression analysis of dependent variables CySSP and PTI against covariates dietary calorie and protein intake, dialysis clinic, Kt/V, age, BMI, CCI, albumin, CRP, NGAL, and IL-6. Dotted lines indicate linear fit and 95% individual confidence interval. (a) log10 transformed variables.