High diet quality indices associated with lower risk of lipid profile abnormalities in Taiwanese kidney transplant recipients

Cardiovascular disease (CVD) and its risk factors seem to be linked with deteriorated graft function and persists as the major cause of mortality in kidney transplant recipients (KTRs). Diet quality is associated with CVD prevention in the healthy population, however, less study focuses on KTRs. The study aimed to determine the association between diet quality indices and lipid profile abnormalities as risk factors for CVD in KTRs. This prospective study enrolled 106 KTRs who had functioning allografts from September 2016. Lipid profiles included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG) and were based on the National Cholesterol Education Program Adult Treatment Panel III recommendations. Three-day dietary data were collected by a well-trained registered dietitian. The Alternative Healthy Eating Index-Taiwan (AHEI-Taiwan), Alternative Healthy Eating Index-2010 (AHEI-2010), and Healthy Eating Index-2015 (HEI-2015) scores were calculated and divided into quartiles and compared accordingly. KTRs’ mean LDL-C, HDL-C, TC, and TG levels were 119.8 ± 36.6 mg/dL, 52.0 ± 17.9 mg/dL, 205.8 ± 43.9 mg/dL, and 160.2 ± 121.6 mg/dL, respectively. Compared with the lowest quartile, only the highest quartile of AHEI-Taiwan had lower TC and LDL-C levels. After adjustment for age, gender, energy, Charlson comorbidity index, transplant duration, and dialysis duration, logistic regression analysis revealed that the highest quartile of AHEI-Taiwan had 82% (odds ratio [OR], 0.18; 95% confidence interval [CI] 0.04–0.72, p < 0.05) lower odds of high TC and 88% (OR 0.12; 95% CI 0.03–0.58, p < 0.05) lower odds of high LDL-C, and the highest quartile of HEI-2015 had 77% (OR 0.23; 95% CI 0.05–0.95, p < 0.05) lower odds of high LDL-C. Higher adherence to a healthy diet as per AHEI-Taiwan and HEI-2015 guidelines associated with lower risk of lipid profile abnormalities in KTRs.


Data collection and definitions of abnormal lipid profiles
Characteristics data encompass age, gender, dialysis duration, transplant duration, immunotherapy used, body height, weight, body mass index, albumin, estimated glomerular filtration rate, creatinine, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG) and total cholesterol (TC) which were obtained from the participants' electronic medical records in the same month as the interview.
Lipid profile abnormalities were defined as follows: serum TC levels ≥ 200 mg/dL, serum TG levels ≥ 150 mg/ dL, serum LDL-C levels ≥ 100 mg/dL, and serum HDL-C < 40 mg/dL for men and < 50 mg/dL for women; these values were based on the National Cholesterol Education Program Adult Treatment Panel III recommendations 12 .
Dietary data were collected through a 3-day dietary records (by self-reported and including 2 weekdays and 1 day on the weekend) and were assessed by a well-trained registered dietitian during regular followed clinics.Dietary food and nutrient intake were calculated according to Taiwan's Ministry of Health and Welfare Food and Drug Administration database and analyzed by using CofitPro nutrition analysis software (version 1.0.0,Cofit HealthCare, Taipei, Taiwan), as described previously 6 .
AHEI-Taiwan is more appropriate for measuring Taiwanese dietary intake and more convenient for calculating the cereal proportion of wholegrain consumption 11 .AHEI-Taiwan scores range from 0 (low diet quality) to 87.5 (high diet quality) and includes nine components: low trans fats; moderate alcohol consumption; high polyunsaturated fatty acid and saturated fatty acid ratio, fruit, vegetable, and wholegrain ratio; white and red meat ratio (white meat was defined as poultry, fish and seafood; red meat was defined as beef, pork and processed meat); nut and soybean intake; and vitamin used.Each component was ranging 0-10 points except vitamin used was ranging 2.5-7.5 points (Table 2).AHEI-2010 13 was modified from AHEI according to the 2015-2020 Dietary Guidelines for Americans, with total scores ranging from 0 (low diet quality) to 110 (high diet quality).AHEI-2010 includes 11 food components: low trans fats, red meat, sodium, and sugar intake with high scores; moderate alcohol consumption with high scores; and high intake of n-3 polyunsaturated fatty acid, fruit, vegetable, wholegrain, and nut and soybean.Each component was ranging 0-10 points (Table 3).HEI-2015 14 was developed according to the 2015-2020 Dietary Guidelines for Americans and Diet Pyramid in the United States, with total scores ranging from 0 (low diet quality) to 100 (high diet quality).HEI-2015 has 13 food components: high intake ratio of unsaturated fatty acid and saturated fatty acid; fruit, whole fruit, vegetable, green leaf vegetable, wholegrain, milk, total meat, seafood, and plant with high scores; and low intake of saturated fatty acid, refined grain, sodium, and sugar with high scores.Each component was ranging 0-10 points except fruit, whole fruit, vegetable, green leaf vegetable, total meat, seafood, and plant were ranging 0-5 points (Table 4).

Statistical analysis
SAS 9.4 version software (SAS Institute, Cary, NC, USA) was used for statistical analyses.Data are presented as percentage, interquartile range, mean and standard deviation, as appropriate.The associations between diet quality and lipid profile abnormalities as risk factors for CVD by logistic regression analysis (adjusted for age, gender, energy intake, transplant and dialysis duration, and Charlson comorbidity index) based on the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines 15 .Data are described as odds ratios (ORs) with 95% confidence intervals (95% CIs) and p value < 0.05 was significance.

Comparison of the lowest and highest quartiles of HEI-2015 scores
Most KTRs had inadequate wholegrain and milk consumption, with the scores being less than half of the corresponding scores recommended in HEI-2015.Compared with the lowest quartiles, the highest quartiles of HEI-2015 had significantly higher total scores and scores for the ratio of unsaturated and saturated fatty acid, saturated fatty acid, fruit, whole fruit, vegetable, green leaf vegetable, wholegrain, refined grain, and sodium consumption.

OR of dietary indices and CVD risk factors
Logistic regression analysis is presented in Table 5. Model 2 was adjusted for age, gender, energy intake, Charlson comorbidity index, transplant duration, and dialysis duration based on the KDOQI guidelines (15).The highest quartiles of AHEI-Taiwan had 82% (OR 0.18; 95% CI 0.04-0.72,p for trend < 0.05) lower odds of high TC levels and 88% (OR 0.12; 95% CI 0.03-0.58,p for trend < 0.05) lower odds of high LDL-C levels.No significant association was observed between the lipid profile and AHEI-2010 scores.However, the highest quartiles of HEI-2015 had 81% (OR 0.19; 95% CI 0.04-0.83,p for trend < 0.05) lower odds of high LDL-C levels.

Discussion
Our results demonstrated that KTRs in the highest quartiles of AHEI-Taiwan had an 82% and 88% lower odds of high TC and high LDL-C levels, respectively.Moreover, the highest quartiles of HEI-2015 had 77% lower odds of high LDL-C levels than the lowest quartiles of these dietary indices after adjustment for age, gender, energy intake, transplant and dialysis duration, and Charlson comorbidity index.CVD remains one of the leading causes of KTR mortality and increases graft function loss 2 .High diet quality represents healthy dietary guidance from dietary indices and is associated with lower risk of all-cause, cancer, and mortality 16 .In the present study, the mean total HEI-2015 and AHEI-2010 scores were 69.1 and 62.1, which were higher than those reported in some countries: 45.7 in a Brazilian population 17 ; 42.2 and 43.8 in Chinese male and female populations, respectively 18 ; and 52.4 and 47.6 in U.S. male and female populations, respectively 13 .High diet quality, as measured using dietary indices based on foods, nutrients and dietary patterns, is associated with a low risk of chronic disease 19 .In the Women's Health Initiative Observational Study 20 , which included postmenopausal women cohort study, demonstrated that the highest quintile of score had a 23% reduction in the risk of CVD (HR, 0.77; 95% CI 0.70-0.84)and a 30% reduction in the risk of heart failure (HR, 0.70; 95% CI 0.59-0.82)compared with the lowest quintile.Consistent with the results of a prospective analysis of U.S. male health professionals 21 , the highest quintile of AHEI scores had an 11%-20% lower risk of major chronic disease (CVD, cancer, or death) as well as a 28%-39% education in CVD risk compared with lowest quintile.However, over 24 years of follow-up, the highest quintile of the AHEI-2010 scores (13) also had a significantly lower risk of CVD (24%), diabetes (33%), CHD (31%), stroke (20%), and major chronic disease risk (19%) than the lowest quintile.A recent review 22 also concluded that higher diet quality for AHEI was associated with a lower incidence of all-cause mortality and CVD mortality; higher diet quality for HEI also associated with a lower risk of CVD mortality.
Previous study has been demonstrated that participants with higher AHEI scores had lower LDL-C and TG levels 23 .Kauffman et al. 10 also indicated that a higher AHEI score was associated with lower serum LDL-C and TC levels.Consistently, our data indicated that KTRs with higher AHEI-Taiwan scores had 82% and 88% lower odds of high TC and high LDL-C levels, respectively, but TG was not significantly different.No significant difference in lipid profile parameters was noted between the highest and lowest quartiles of AHEI-2010.Similarly, Ziaee et al. 8 demonstrated that higher HEI scores were related to lower LDL-C levels among 235 participants.Another study found that higher meat and sweetened beverage intake was associated with higher levels of LDL-C, TC, TG, and lower levels of HDL-C 24 .
The possible mechanism of high diet quality had a lower risk of lipid profile abnormalities is related to the AHEI-2010, AHEI-Taiwan, and HEI-2015 guidelines, which emphasize a high polyunsaturated fatty acids intake in the form of nuts and soybeans, because their anti-inflammatory properties prevent atherosclerosis 25 .Wholegrain foods are a rich source of dietary fiber that binds cholesterol and bile acids in the intestinal lumen to decrease serum TC and LDL-C levels 26 .They can also enhance the cholesterol-lowering effect of statins 27 .Fruits and vegetables are rich sources of fiber, antioxidants, and polyphenols, which decrease serum TC and LDL-C levels 28 , prevent the oxidation of cholesterol in the arteries 29 , and decrease systemic inflammation through cell signaling processes, thus preventing atherosclerosis and CVD development 30 .An intervention study 31 concluded that consuming three servings of fruit and two servings of vegetables every day for 4 weeks significantly decreased TC by 15.29 mg/dL and LDL-C by 10.45 mg/dL in line with the recommendations of AHEIT-Taiwan regarding vegetable and fruit consumption 11 .
Red meat is rich in saturated fatty acids, which increases LDL-C levels by enhancing apolipoprotein B-containing lipoprotein production and inhibiting LDL receptor activity 32 .Substituting saturated fats with polyunsaturated fat as cooking oil reduces LDL-C levels and the TC to HDL-C ratio, which is beneficial for coronary heart disease prevention 33 .Alcohol consumption was reported to be positively associated with TG levels and inversely associated with HDL-C levels 34 .Another study noted that high alcohol consumption caused significantly increased LDL-C, TC, and TG levels and decreased the levels of HDL-C 35 .By contrast, moderate alcohol consumption seems to have a protective effect on the heart.Taken together, the aforementioned evidence supports that a healthy dietary index inclusive of high polyunsaturated fatty acids, vegetables, whole grains, fruits, and less saturated fatty acids and red meat consumption may reduce the risk of lipid disorders.AHEI-Taiwan was modified from AHEI according to Taiwanese dietary recommendations 11 which is more adapted to Taiwanese dietary patterns and has a more protective effect on abdominal lipid profiles in KTRs.
Few studies have evaluated the association between diet quality and metabolic disorders in KTRs, especially in Taiwan.A healthy diet can minimize the risk of lipid profile abnormalities, thus providing protection against CVDs, improving quality of life, and extending the graft kidney survival rate.
This study has some limitations.First, the cross-sectional design precluded the determination of causality although we used a 24-h recall method collected a 3-day dietary records to increase the precision of nutritional assessment.Future well-designed randomized controlled trials should assess whether our observations can be extrapolated to other KTRs.Second, different assessment methods for dietary food and nutrients intake and determining diet quality indices may have contributed to inconsistent findings.Further development of validated diet quality indices as a dietary assessment tool is extremely desirable for increasing clinician assessment www.nature.com/scientificreports/efficiency to promote healthy diet education.Finally, this study's findings may remain be restricted by other potential or unmeasured confounding factors, such as immunological therapy or family history.However, our findings focus attention on a better diet quality which is an important affecting factor was associated with the preventions of lipid profile abnormalities.

Conclusion
This prospective study demonstrated that higher adherence to healthy diet quality, such as AHEI-Taiwan and HEI-2015, was associated with lower lipid profile abnormalities as risk factors for CVD in KTRs.Notably, AHEI-Taiwan is developed according to Taiwan's dietary recommendation which is more closely to Taiwanese dietary culture.Further study regarding to diet quality and the education strategy of health promoting to prevent the abnormalities lipid profiles are warranted for long-term KTRs. https://doi.org/10.1038/s41598-023-46736-2

Table 1 .
Clinicodemographic and dietary characteristics of KTRs stratified by the lowest and highest quartiles of AHEI-Taiwan, AHEI-2010, and HEI-2015 scores.Data were represented as mean ± SD or n (%) as appropriate.AHEI Alternative Healthy Eating Index, HEI Healthy Eating Index, SD Standard deviation, RT Renal transplant, BMI Body mass index, TC Total cholesterol, LDL-C Low-density lipoprotein cholesterol, HDL-C High-density lipoprotein cholesterol, TG Triglyceride, eGFR Estimated glomerular filtration rate.*p < 0.05 and † p < 0.01.

Table 2 .
Comparison of the lowest and highest quartiles of AHEI-Taiwan scores and components.Data are presented as mean ± standard deviation.Q Quartile, AHEI Alternative Healthy Eating Index, S Servings, M Male, F Female, PSR Polyunsaturated-to-saturated fatty acid ratio.*p < 0.05; † p < 0.01; ‡ p < 0.001.

Table 4 .
Comparison of the lowest and highest quartiles of HEI-2015 scores.Data are presented as mean ± standard deviation.USR Unsaturated and saturated fatty acid ratio, SFA Saturated fatty acid.

Table 5 .
Odds ratio of dietary indices and cardiovascular disease risk factors.Data were represented as odds ratio and 95% confidence interval.Model 1 adjusted for age and gender.Model 2 adjusted for age, gender, energy intake, renal transplant and dialysis duration, and Charlson comorbidity index.Q Quartile, OR Odds ratio, CVD Cardiovascular disease, CI Confidence interval, AHEI Alternative Health Eating Index, TC Total cholesterol, LDL-C Low-density lipoprotein cholesterol, HDL-C High-density lipoprotein cholesterol, TG Triglyceride.*p < 0.05; † p < 0.01.