2.6. Biochemical Parameters
Monthly fasting blood tests were performed in each selected hospital through automated and standardized methods. The laboratory test results were identical in different laboratories in selected hospitals. The studied biochemical parameters were total cholesterol (TC, mg/dL), triglyceride (TG, mg/dL), fasting blood glucose (FBG, mg/dL), hemoglobin (Hgb, g/dL), calcium (Ca, mg/dL), phosphorous (PO4, mg/dL), calcium and phosphate product (Ca × PO4), intact parathyroid hormone (iPTH, pg/mL), albumin (Alb, mg/dL), creatinine (Cr, mg/dL), and potassium (K, mEq/L). Other biochemical parameters were subsequently analyzed in the laboratory of Taipei Medical University Hospital, including values of low density lipoprotein cholesterol (LDL-C, mg/dL), high density lipoprotein cholesterol (HDL-C, mg/dL), homocysteine (Hcy, µmol/L) and high sensitivity C-reactive protein (hs-CRP, mg/dL).
2.7. The Alternative Healthy Eating Index (AHEI) in Hemodialysis Patients
The dietary data were assessed using the 24-hour dietary recall form in paper format [
22]. A qualified dietician instructed patients to complete the assessment forms on one dialysis day, one non-dialysis day, one non-dialysis day during the weekend, including meal time, meal location, food name, brand names, ingredients, portion or weight of food, and the cooking methods, oils used [
20,
23]. To confirm the data collected, dietitians used the 24-hour dietary recall form with common utensils to ask patients face-to-face or by phone call, as described previously [
20,
23,
24,
25]. If patients did not complete the form for one assessment, those with missing dietary intake data were not included in the analysis. Nutrients were analyzed using nutrition analysis software, e-Kitchen (Nutritionist edition, Enhancement plus 3, version 2009, Taichung, Taiwan), based on the Food Nutrition Database in Taiwan [
26].
Index scores such as HEI and AHEI have been applied in different populations to investigate the association between dietary intake and health outcomes [
8,
10,
12,
14,
15,
16,
18,
24,
27,
28]. The AHEI was stronger in predicting major chronic diseases and CVD risks as compared to the original HEI [
8,
11]. The AHEI was used to examine the association between dietary intake and cardiovascular risks and event in type-2 diabetes patients in Taiwan. The AHEI index has shown its validity and applicability in Taiwan food culture [
28]. Therefore, the AHEI-2010 was adapted and used in the current study.
In 2000, the NKF proposed that hemodialysis patients should avoid food containing high levels of phosphorus such as nuts, legumes, dairy products, and whole grains [
29]. However, in 2016, the nutritional recommendations were modified; it was proposed that the restrictions on those items be eased, as they contain dietary fiber and healthy nutrients which may improve outcomes [
30]. In addition, it was suggested that less restrictive dietary approaches be adopted to improve the autonomy and liberty of dialysis management [
19]. Therefore, the intake of whole fruits and total vegetables was scored according to the Daily Food Guides in Taiwan [
7], and the deciles of distribution of actual intake of whole grains, nuts and legumes, dairy products were used to obtain the index score. Lowe deciles of consumption of whole grains, nuts and legumes, and dairy products were suggested to obtain a maximum score.
Higher consumption of sugar-sweetened beverages are associated with higher metabolic syndrome [
31] and mortality [
32]. Therefore, no sugar-sweetened beverages and fruit juice was suggested [
33], and a maximum score was obtained.
The International Agency for Research on Cancer (IARC) announced that the consumption of processed meat is carcinogenic for humans (Group I) [
34], and that it increases all-cause mortality [
35,
36]. However, the evidence on red meat consumption and the risk of cancer are not consistent; furthermore, red meat is rich in protein, vitamins and minerals, especially Heme-iron. Those nutrients are important for hemodialysis patients [
29]. Therefore, red and/or processed meat in AHEI-2010 was divided into two items (red meat, and processed meat) in the current study. No consumption of processed meat, and consuming less than 1.5 servings a day of red meat were suggested, and the maximum score was obtained.
The consumption of at least 1 serving of fish per week (especially spices rich in
n-3 fatty acids eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) such as salmon, sea bass, sardines, shrimp, trout, and mackerel) was suggested for improving cardiovascular outcomes [
8,
37], and inflammation in hemodialysis patients [
38]. The maximum index score was achieved when the suggestions were met.
The EAT-Lancet commission recommends the consumption of unsaturated fats rather than saturated fats [
33]. Therefore, unsaturated fatty acids (UFAs), rich oils (olive, soy, sunflower, tea, canola, rice, peanut, flax seed, and grape seed) are recommended. When the intake of oils meets the Daily Food Guides [
7], the maximum score was achieved. The ‘UFAs rich oils’ item was used in the current study instead of the ‘PUFAs’ item in AHEI-2010. On the other hand, saturated fatty acids (SFAs) and rich oils (animal or palm oils) are not recommended in the current dietary guidelines. Therefore, patients consuming none of these will get the maximum score.
The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 Alcohol Collaborators suggested that zero alcohol consumption could minimize health risks [
39]; under such circumstances, the maximum score was then obtained. The deciles of distribution of sodium intake were used to obtain the intake score [
8]; the lowest decile was recommended to obtain the maximum score.
In addition, protein energy malnutrition is highly prevalent in hemodialysis patients. Restrictive dietary approaches are one of the causes [
40]. Therefore, adequate energy and protein intake are critically important in securing the nutritional status of hemodialysis patients [
23,
29]. The total grain consumption and total protein intake were suggested based on the level of energy requirements according to the Daily Food Guides [
7]. Furthermore, high biological value protein foods (soy products, meats [pork, beef, lamb, poultry, seafood/fish], and eggs) should account for at least 50% of total dietary protein [
29]. Maximum index scores were obtained when this suggestion was followed.
The original AHEI-2010 items included whole fruits, vegetables, whole grains, sugar-sweetened beverages and fruit juice, nuts and legumes, fresh red meat, processed meat, fish, UFAs rich oils, alcohol and sodium. The modified version of AHEI for hemodialysis patients (AHEI-HD) included additional items such as total grains, total protein foods, high biological value (HBV) proteins, dairy products and SFAs rich oils. Most items were determined from the output of nutrition analysis software, while HBV proteins were calculated by summing the intake of soy products, meats (pork, beef, lamb, poultry, seafood/fish), and eggs. The maximum possible score of all items was 10. Intermediate intakes were scored proportionately between a minimum of 0 and a maximum of 10. Therefore, the sum scores ranged from 0 to 110 for the AHEI-2010 scale, and from 0 to 160 for the AHEI-HD scale.
2.8. Statistical Analysis
The continuous variables were checked for normality using a Shapiro-Wilk’s test (normal if
p value > 0.05) [
41], histograms, normal Q-Q plots and box plots. Descriptive analysis was used to describe the distributions of study variables via the mean and standard deviation for normally distributed variables, median and interquartile range for abnormally distributed variables, and frequency and percentage for categorical variables. The independent-samples
t-test, Mann-Whitney U test, or Chi-square test were used to test the distributions of the study variables appropriately.
In order to evaluate the construct validity of AHEI-HD, a number of analyses were conducted. Firstly, Spearman correlation was used to estimate the correlation of eating index components, total scores and energy intake, which illustrated the performance of AHEI-2010 and AHEI-HD on assessing diet quality independent of diet quantity. The item-scale correlation was also assessed. Secondly, the principal component analysis (PCA) was used to examine the multidimensional characteristics of AHEI-2010 and AHEI-HD, for which the scree plot test was used. The scree plot is a subjective test, but it was commonly used in previous studies to determine the heterogeneity of the healthy eating index [
10,
27]. Thirdly, the known-group validity was conducted using
t-tests to compare the distribution of AHEI-2010 and AHEI-HD scores between different age groups (<65 years vs. ≥ 65 years), gender (men vs. women), history of diabetes mellitus (DM vs. non-DM).
In addition, criterion validity was assessed via hazard ratios for all-cause mortality by different tertile (categorical model) and by each tertile increment (continuous model) in AHEI-2010 and AHEI-HD index scores. The analysis was conducted using Cox proportional hazards models, as commonly used when examining the association between health eating index and mortality outcome [
10,
27]. Model 1 included eating index scores and all-cause mortality. In model 2, the confounders showed the association with all-cause mortality at
p < 0.25 were selected [
42]. The Spearman correlation among confounders was run to check and avoid co-linearity. If two or more variables moderately or strongly correlated with each other, one representative variable was kept in the multivariate model.
Data were analyzed by using the SPSS for Windows version 20.0 (IBM Corp., New York, USA). The significant level was set at p-value < 0.05.