Clinical Nutrition 40 (2021) 5099e5105

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Clinical Nutrition
journal homepage: http://www.elsevier.com/locate/clnu

Original article

Diet quality and incident chronic kidney disease in the general

population: The Lifelines Cohort Study
Qingqing Cai a, *, Louise H. Dekker a, Petra C. Vinke b, Eva Corpeleijn b,
Stephan J.L. Bakker a, Martin H. de Borst a, Gerjan J. Navis a
a
Department of Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
b
Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

a r t i c l e i n f o s u m m a r y

Article history: Rationale & aims: Healthy dietary patterns have been associated with a lower risk of chronic kidney
Received 2 June 2021 disease (CKD). We aimed to investigate the association of a fully food-based diet quality score assessed by
Accepted 29 July 2021 the Lifelines Diet Score (LLDS) with either incident CKD or eGFR decline in the general population.
Methods: For this study, data from a prospective general population-based Lifelines cohort in the
Keywords: Northern Netherlands was used. Diet was assessed with a 110-item food frequency questionnaire at
Chronic kidney disease
baseline. The LLDS, based on international evidence for dietedisease relations at the food group level,
eGFR decline
was calculated to assess diet quality. For the analysis, the score was divided into tertiles. Logistic
Diet quality
Lifelines Diet Score
regression was performed to evaluate the association of the LLDS at baseline with either incident CKD
(eGFR <60 mL/min/1.73 m2) or a
20% eGFR decline at the second study visit, adjusted for relevant
confounders.
Results: A total of 78 346 participants free of CKD at baseline were included. During a mean (SD) follow-
up of 3.6 ± 0.9 years, 2071 (2.6%) participants developed CKD and 7611 (9.7%) had a
20% eGFR decline.
Participants in the highest tertile of LLDS had a lower risk of incident CKD (fully adjusted OR 0.83, [95%
CI: 0.72e0.96]) and
20% eGFR decline (fully adjusted OR 0.80, [95% CI: 0.75e0.86]), compared with
those in the lowest tertile. Similar doseeresponse associations were observed in continuous LLDS.
Conclusions: Higher adherence to a high-quality diet was associated with a lower risk of incident CKD or

20% eGFR decline in the general population.
© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).

1. Introduction
Chronic kidney disease (CKD) is a growing global public health
issue, affecting 8%e16% of the population worldwide [1]. Diabetes
and hypertension are the most common causes of incident CKD
worldwide [1e3]. The high (cardiovascular) co-morbidity rate,
expensive therapy, and poor outcomes form a high burden for so-
ciety. Healthy diets, often rich in plant-based foods, have been
associated with a lower incidence and slower progression of CKD
[4e7]. Dietary patterns that are considered healthy often share
similar characteristics, encouraging higher consumption of vege-
tables, fruits, legumes, nuts, whole grains, fish, and low-fat dairy,
and lower consumption of red and processed meats, sodium, and
sugar-sweetened beverages [7]. Previous studies illustrated that
the Mediterranean diet, one of the natural healthy dietary patterns,
is associated with a lower risk of CKD development and progression
in the general population [8e12]. However, the Mediterranean diet
score (MDS) is not completely food-based and not fully in accor-
dance with current scientific evidence [13]. For example, recent
evidence shows that sugar-sweetened beverages are associated
with a higher risk of incident CKD and kidney function decline
[5,14], which are not included in the MDS.
The Lifelines Diet Score (LLDS), a fully food-based diet score, has
been developed based on the contemporary international scientific
literature underlying the 2015 Dutch Dietary Guidelines [15,16].
Based on current scientific evidence, nine food groups are consid-
ered positive (vegetables, fruit, whole grain products, legumes and
nuts, fish, oils and soft margarines, unsweetened dairy, coffee, and

* Corresponding author. Department of Medicine, Division of Nephrology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
E-mail address: q.cai@umcg.nl (Q. Cai).

https://doi.org/10.1016/j.clnu.2021.07.033
0261-5614/© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Q. Cai, L.H. Dekker, P.C. Vinke et al.
tea) and three food groups are considered negative (red and pro-
cessed meat, butter and hard margarines, and sugar-sweetened
beverages) in relation to the top-10 chronic diseases in the
Netherlands, e.g., cardiovascular disease and diabetes [15].
Although CKD was not among the chronic diseases considered in
the construction of the 2015 Dutch Dietary Guidelines, cardio-
metabolic diseases that have been taken into account are major
risk factors for impaired kidney function. Hence, the LLDS may be
relevant to assess dietary risk for CKD as well. This assumption,
however, has not been tested.
Therefore, we aimed to investigate the associations of the LLDS
with incident CKD and a
20% eGFR decline in the Lifelines Cohort
Study, a large general population-based cohort. In addition, we
assessed the associations between the MDS, as a well-established
diet score, and these kidney outcomes in the same population for
comparison.
2. Materials & methods
2.1. Cohort design and study population
The Lifelines Cohort Study is a prospective general population-
based cohort study evaluating the health and health behaviors of
more than 160 000 participants in the Northern Netherlands. Par-
ticipants were enrolled in this study between 2006 and 2013
through invitation by their general practitioners and signed the
informed consent before entering the cohort. All the participants
were invited to a second assessment between 2014 and 2019.
Detailed information about the overall design and rationale of the
Lifelines cohort have been described in a previous study [17]. The
Lifelines Cohort Study is conducted according to the principles of
the Declaration of Helsinki and is approved by the medical ethical
review committee of the University Medical Center Groningen.
In the Lifelines cohort, 152 728 participants were older than 18
years. About 100 648 participants returned for the second assess-
ment until 2017. We excluded participants with CKD (defined as
having an eGFR using the Chronic Kidney Disease Epidemiology
Collaboration equation (CKD-EPI) [18] <60 mL/min/1.73 m2) at
baseline (1916 participants) and those with missing values of di-
etary intake information (2064 participants) or serum creatinine
(7436 participants). To evaluate potential under- or over-reporting
on the food frequency questionnaire, the reliability of energy intake
was evaluated based on energy intake/basal metabolic rate (EI/
BMR) and applying the Goldberg cut-off [19,20]. EI/BMR <0.5 and
>2.75 were considered unreliable; EI/BMR between 0.5 and 2.75
were considered reliable. We excluded those with unreliable en-
ergy intake in this study (10 886 participants). Eventually, a total of
78 346 participants with the age range of 18e90 years were
included in the present study.
2.2. Lifelines Diet Score
LLDS is established according to the integrated evidence-based
advice on the prevention of the top-10 chronic diseases and three
casual risk factors in the Netherlands [15,16]. Coronary heart dis-
ease, stroke, heart failure, type 2 diabetes mellitus, chronic
obstructive pulmonary disease, colorectal cancer, breast cancer,
lung cancer, dementia and cognitive decline, and depression are the
top-10 chronic diseases in the Netherlands and three casual risk
factors (blood pressure, LDL-cholesterol, and body weight) related
to cardiovascular disease or diabetes were included. The 2015
Dutch Dietary Guidelines are formulated by systematic evaluation
of the international scientific evidence about the relationships of
the foods, nutrients, and dietary patterns with chronic diseases and
casual risk factors. Thus, it is an evidence-based guideline rather
5100
Clinical Nutrition 40 (2021) 5099e5105
than a cultural preference- or expert opinion-based guideline.
Based on the scientific evidence underlying the 2015 Dutch Dietary
Guidelines, 12 food groups were identified as being convincingly
associated with health and were included in the previously estab-
lished LLDS [15,16]. The LLDS ranks intake of nine positive food
groups (vegetables, fruit, whole grain products, legumes and nuts,
fish, oils and soft margarines, unsweetened dairy, coffee, and tea)
and three negative food groups (red and processed meat, butter and
hard margarines, and sugar-sweetened beverages). The food items
of these 12 food groups are shown in Supplemental Table 1.
Dietary intake was assessed by a self-administered 110-item
semi-quantitative food frequency questionnaire (FFQ) in the Life-
lines cohort [17]; it included questions on the frequency and
portion size of food items over the previous month. The develop-
ment of the food-based LLDS and its application in Lifelines has
been described elsewhere [16]. In short, daily intake for each pos-
itive and negative food group (in gram/1000 kcal) was categorized
into quintiles, awarding 0 to 4 points (negative groups scored
inversely). The LLDS was obtained by the sum of 12 component
scores, ranging from 0 to 48, then divided into tertiles for further
analyses.
2.3. Mediterranean diet score
In order to ascertain the associations between diet quality and
kidney outcomes in the same population by a well-established in-
dex of a healthy dietary pattern, we calculated the MDS through a
nine-point score by Trichopoulou et al. [13]. Five positive (vegeta-
bles, legumes, cereal, fruit and nuts, and fish), three negative
(meats, poultry, and dairy products) food groups, and alcohol
intake were included in the MDS. Participants received 1 point if
their intake was above the sex-specific median in gram per day for
positive food components; intake below the median was scored 1
for negative components. For alcohol, a value of 1 was given to
men who consumed between 10 and 50 g/day or to women who
consumed between 5 and 25 g/day. The MDS varies between
0 and 9.
2.4. Assessment of other baseline covariates
Self-administered questionnaires were used to assess de-
mographics (age and sex), sociodemographic characteristics (edu-
cation level), and health-related behaviors (smoking status and
physical activity). Education level was classified into four groups
(low: never been to school or elementary school only or lower
vocational or secondary school; middle: intermediate vocational
school or intermediate/higher secondary school; high, higher
vocational school or university; unknown or no answer). Smoking
status was categorized as never, former, and current smokers. The
validated Short Questionnaire to ASsess Health-enhancing physical
activity (SQUASH) questionnaire was used to evaluate time spent
on non-occupational moderate-to-vigorous physical activity (mi-
nutes/week). Body mass index (BMI) was calculated as weight (kg)
divided by height squared (m2). Blood and urine laboratory as-
sessments have been published previously in detail [17]. Serum
creatinine was measured by an enzymatic method traceable to
isotope dilution mass spectrometry on a Roche Modular analyzer
(Roche Diagnostics, Mannheim, Germany). Estimated GFR was
calculated using the Chronic Kidney Disease Epidemiology Collab-
oration equation (CKD-EPI) [18]. The prevalence of cardiovascular
disease including coronary artery disease, heart failure, and/or
stroke was based on the self-reported questionnaire. Participants
were considered as having diabetes if they had self-reported dia-
betes and/or a non-fasting plasma glucose
11 mmol/L and/or a
measured glycated hemoglobin (HbA1c)
6.5% and/or use of oral
Q. Cai, L.H. Dekker, P.C. Vinke et al. Clinical Nutrition 40 (2021) 5099e5105

anti-diabetics and/or insulin. Hypertension was defined as blood between 1.3 times (whole-grain products) and 3.7 times (fruits)
pressure >140/90 mmHg or the use of antihypertensive higher than that in the lowest tertile. Intake of negative food groups
medication. was between 1.3 times (red and processed meat) and 5.1 times
(sugar-sweetened beverages) higher in the lowest tertile compared
2.5. Kidney outcomes with that in the highest tertile.

The primary outcome of this study was incident CKD, defined as
a de novo occurrence of an eGFR <60 mL/min/1.73 m2 at the second
study visit. The secondary outcome was a
20% eGFR decline at the
second study visit relative to baseline.
2.6. Statistical analysis
Baseline characteristics are presented according to the tertiles of
LLDS. Data are presented as mean ± standard deviation, median
(interquartile range), or percentage, as appropriate. Multivariable
logistic regression was applied to evaluate the association of the
LLDS (in categories as tertiles of LLDS or as a continuous variable
per standard deviation (SD) increase of LLDS) with either incident
CKD or a
20% eGFR decline, adjusted for potential confounders.
Odds ratios (OR) and 95% confidence intervals (CI) were calculated
across the tertiles of LLDS. In logistic regression, initially, we
adjusted for age and sex (Model 1). Then, we further adjusted for
physical activity, smoking status, total energy intake, total alcohol
intake, and education level (Model 2). After that, baseline eGFR,
BMI, diabetes, hypertension, and cardiovascular disease were
further adjusted (Model 3). The same models were used to evaluate
the associations of the tertiles of MDS and continuous MDS (per SD
increase) with both kidney outcomes. The associations of the
continuous LLDS (per 1 point increase) with kidney outcomes are
visualized by fitting multivariable logistic regression analyses ac-
cording to model 3 using the median value of the LLDS as the
reference value. A two-tailed P value <0.05 was considered statis-
tically significant. The statistical analyses were conducted using R
version 3.4.2 (Vienna, Austria).
3. Results
Among the 78 346 participants in the study, 45 761 (58.4%)
participants were women. The mean (±standard deviation) age of
all participants was 45.8 ± 12.6 years old. The sum of LLDS ranged
from 3 to 47. Table 1 shows the median intake of nine positive and
three negative food groups included in the LLDS across tertiles of
LLDS. Intake of positive food groups in the highest tertile was
3.1. Baseline characteristics
Baseline characteristics according to LLDS tertiles are summa-
rized in Table 2. Participants in the highest LLDS tertile tended to be
older, more often women, with lower baseline eGFR, and a higher
prevalence of diabetes, hypertension, and cardiovascular disease,
compared with those in the lowest tertile. Participants in the
highest tertile had a higher attained education, were less often
current smokers, more physically active, had lower total energy
intake, higher alcohol intake, higher protein intake, higher carbo-
hydrate intake, and lower fat intake. A moderate positive rank
correlation was found between the LLDS and the MDS (Spearman
correlation coefficient: 0.50, P < 0.001).
3.2. LLDS and kidney outcomes
During a mean (SD) follow-up time of 3.6 ± 0.9 years, 2072
(2.6%) participants developed CKD and 7611 (9.7%) had an eGFR
decline
20%. Table 3 shows the multivariable logistic regression
analyses of the associations between the LLDS and incident CKD or
eGFR decline
20%. In fully-adjusted analyses, participants in the
highest tertile of LLDS had a lower risk of incident CKD (OR 0.83
[95% CI: 0.72e0.96]) or eGFR decline
20% (OR 0.80 [95% CI:
0.75e0.86]) compared with the lowest tertile. Per SD increase, the
LLDS was associated with a 9% lower risk of incident CKD and a 10%
lower risk of eGFR
20% decline. The correlations of the continuous
LLDS with incident CKD and eGFR decline
20% fit by multivariable
logistic regression analyses are illustrated in Fig. 1.
3.3. MDS and kidney outcomes
The associations between the MDS and kidney outcomes by
logistic regression analyses are shown in Table 4. In fully adjusted
models, participants in the highest tertile of MDS had a lower risk
of
20% eGFR decline (OR 0.92 [95% CI: 0.86e0.98]), compared with
those in the lowest tertile, while a borderline association was found
between MDS and incident CKD (OR highest vs. lowest tertile 0.88
[95% CI: 0.76e1.01, P for trend ¼ 0.071). Upon continuous analyses,

Table 1
The consumption of 12 food groups included in LLDS across the tertiles of LLDS.

Tertiles of LLDS P for trend

T1 T2 T3
N ¼ 27 313 N ¼ 28 864 N ¼ 22 169

LLDS (range) 3e21 22e27 28e47

Positive food groups (gram/1000 kcal)
Vegetables 35 (23e50) 48 (33e66) 65 (47e88) <0.001
Fruits 29 (11e58) 61 (31e103) 107 (63e148) <0.001
Whole grain products 47 (33e63) 56 (40e71) 62 (46e77) <0.001
Legumes & nuts 6 (3e11) 9 (4e15) 12 (7e19) <0.001
Fish 3 (0e6) 5 (2e8) 8 (5e12) <0.001
Oil and soft margarines 5 (2e12) 8 (2e15) 10 (3e16) <0.001
Unsweetened dairy 50 (18e95) 79 (37e134) 112 (62e173) <0.001
Coffee 167 (76e252) 210 (124e297) 251 (170e339) <0.001
Tea 46 (7e118) 98 (30e189) 165 (81e277) <0.001
Negative food groups (gram/1000 kcal)
Red and processed meat 36 (27e45) 33 (24e42) 28 (18e38) <0.001
Butter and hard margarines 15 (8e22) 11 (5e18) 7 (2e12) <0.001
Sugar-sweetened beverages 82 (39e144) 39 (13e81) 16 (3e45) <0.001

Data are presented as median intake with 25th-75th quartiles.

5101
Q. Cai, L.H. Dekker, P.C. Vinke et al. Clinical Nutrition 40 (2021) 5099e5105

Table 2
Baseline characteristics based on tertiles of LLDS.

Total Tertiles of LLDS

T1 (3e21) T2 (22e27) T3 (28e47) P for trend

Number 78 346 27 313 28 864 22 169

Demographics
Age (year) 45.8 ± 12.6 41.8 ± 12.3 46.3 ± 12.2 50.2 ± 12.0 <0.001
Sex, women (%) 58.9 47.9 58.4 71.3 <0.001
Clinical factors
Serum creatinine (mmol/L) 73.3 ± 12.2 74.9 ± 12.4 73.4 ± 12.1 71.10 ± 11.6 <0.001
eGFR (mL/min/1.73 m2) 95.9 ± 14.3 98.9 ± 14.7 95.4 ± 14.0 92.9 ± 13.6 <0.001
BMI (kg/m2) 26.0 ± 4.2 26.0 ± 4.3 26.1 ± 4.1 25.9 ± 4.10 <0.001
Systolic blood pressure (mmHg) 125.7 ± 15.2 125.8 ± 14.6 125.9 ± 15.4 125.3 ± 15.7 <0.001
Diastolic blood pressure (mmHg) 73.9 ± 9.3 74.0 ± 9.3 74.1 ± 9.3 73.6 ± 9.1 <0.001
Diabetes (%) 3.1 2.2 3.3 3.9 <0.001
Hypertension (%) 22.0 18.1 22.4 26.3 <0.001
Cardiovascular disease (%) 2.6 2.2 2.7 3.0 <0.001
Health-related behaviors
Physical activity (minutes/week) 195 (70e375) 155 (60e330) 195 (75e365) 240 (120e420) <0.001
Smoking status (%)
Never 47.3 47.3 47.7 47.0
Former 36.1 29.8 36.9 42.8 <0.001
Current 16.6 22.9 15.4 10.2
Total energy intake (kcal/day) 2076 ± 607 2285 ± 658 2069 ± 567 1826 ± 482 <0.001
Total protein intake (gram/1000 kcal) 37.2 ± 5.5 35.0 ± 5.0 37.4 ± 5.2 39.6 ± 5.6 <0.001
Total carbohydrate intake (gram/1000 kcal) 112.2 ± 13.8 111.5 ± 14.0 111.6 ± 13.8 113.8 ± 13.7 <0.001
Total fat intake (gram/1000 kcal) 39.3 ± 5.5 40.9 ± 5.4 39.5 ± 5.2 37.1 ± 5.3 <0.001
Total alcohol intake (gram/day) 4.0 (0.9e10.4) 5.0 (1.0e12.3) 4.0 (0.9e10.3) 3.5 (0.9e9.0) <0.001
Socioeconomic status
Education (%)
Low 28.7 22.9 28.2 27.7
Middle 39.9 44.5 39.3 35.0
High 31.0 25.2 32.0 36.8 <0.001
Unknown/no answer 0.4 0.4 0.4 0.5

Data are presented as mean ± standard deviation, median (interquartile range), or percentage, as appropriate.

Table 3
Associations of LLDS with incident CKD and eGFR decline
20% by logistic regression analyses.

Tertiles of LLDS Continuous LLDS

OR (95% CI) OR (95% CI) per SD increase

T1 T2 T3 P for trend P value

Incident CKD
Model 1 1.00 0.82 (0.73e0.92) 0.72 (0.64e0.82) <0.001 0.86 (0.82e0.90) <0.001
Model 2 1.00 0.78 (0.69e0.88) 0.66 (0.58e0.75) 0.009 0.82 (0.78e0.86) 0.001
Model 3 1.00 0.88 (0.77e1.01) 0.83 (0.72e0.96) 0.012 0.91 (0.85e0.96) 0.001
eGFR decline
20%
Model 1 1.00 0.95 (0.90e0.99) 0.83 (0.78e0.88) <0.001 0.92 (0.89e0.94) <0.001
Model 2 1.00 0.94 (0.89e0.99) 0.81 (0.76e0.87) <0.001 0.90 (0.89e0.93) <0.001
Model 3 1.00 0.93 (0.88e0.99) 0.80 (0.75e0.86) <0.001 0.90 (0.87e0.92) <0.001

Model 1. Adjusted for age and sex.

Model 2. Model 1 plus physical activity, smoking status, total energy intake, total alcohol intake, and education level.
Model 3. Model 2 plus baseline eGFR, BMI, diabetes, hypertension, and cardiovascular disease.

small but statistically significant associations were observed for
both incident CKD and eGFR decline (Table 4).
4. Discussion
In this large general population-based cohort, higher adherence
to the contemporary, food-based LLDS was associated with a lower
risk of incident CKD and
20% GFR decline. Per SD increase of the
LLDS, a 9% reduction of incident CKD and a 10% reduction of a
20%
eGFR decline during 3.6 years follow-up was observed, indepen-
dent of known confounding factors. For comparison, the MDS, a
well-established score for diet quality, was associated with kidney
outcomes as well, although the effect size was small and borderline
significant for incident CKD after full adjustment. The significant
associations of LLDS with kidney outcomes suggest that the
5102
benefits of a healthy diet, according to the LLDS, go beyond the
chronic diseases the score and guidelines were based on, and may
also have implications for the prevention of CKD.
The associations between several individual nutrients/foods and
the development and progression of CKD or kidney function
decline have been investigated extensively [7,21e26]. However,
compared with studies targeting individual nutrients or food
products, diet scores reflecting the overall diet are more informa-
tive because they provide a broader picture of habitual dietary
behavior [27,28]. In addition, diet scores have been developed to
quantify the complex food composition for scientific analysis and
evaluation and can be potentially used across different populations
[28]. Many diet scores have already existed, some reflecting natural
diets (e.g., the Mediterranean diet) [13], some pre-designed (e.g.,
the DASH diet) [29], but a fully food-based diet score, in line with
Q. Cai, L.H. Dekker, P.C. Vinke et al.
Fig. 1. Associations of LLDS with incident CKD and eGFR decline≥20%. Data were fit
by logistic regression using the median value of LLDS as the reference value (odds
ratio ¼ 1). The odds ratio of incident CKD (A) or a
20% eGFR decline (B) are shown,
adjusted for age, sex, physical activity, smoking status, total energy intake, total alcohol
intake, education level, baseline eGFR, BMI, diabetes, hypertension, and cardiovascular
disease. The black line represents the adjusted odds ratio and the grey area represents
the 95% confidence interval.
current scientific evidence is scarce. This is relevant, considering
the increasing recognition of the relevance of food-based guide-
lines [15]. The LLDS was developed based on the scientific evidence
underlying the food-based 2015 Dutch Dietary Guidelines by
ranking relative consumption of positive and negative food groups
[15,16]. The LLDS is a diet score based on contemporary scientific
evidence, reflecting primarily within-population differences in the
healthfulness of the diet. A recent study reported that diet quality
assessed by LLDS was associated with a lower risk of all-cause
mortality in the general population and in the patients with type
2 diabetes in the Lifelines cohort [30]. Nevertheless, when applied
with a population-based quintile approach, the LLDS can also be
generalized to other populations.
5103
Clinical Nutrition 40 (2021) 5099e5105
The LLDS is characterized by more plant-based and less animal-
based food consumption and can be a useful tool to evaluate the
overall diet quality of individuals [16]. The Mediterranean diet is
characterized by high intakes of vegetables, legumes, fruits and
nuts, cereal, and fish, low intake of meat, poultry, and dairy, as well
as moderate alcohol consumption [13]. In addition to these food
groups, the LLDS includes other positive/healthy food groups like
oil and soft margarines, unsweetened dairy, coffee, and tea, and
negative/unhealthy food groups like butter and hard margarines
and sugar-sweetened beverages. Alcohol intake was not included in
the LLDS, but it was considered as a lifestyle factor and was adjusted
for in the model. In the current study, we included the assessment
of MDS with kidney outcomes to show that diet quality in our
population, assessed by an independent and well-established in-
dex, is associated with kidney outcomes. The MDS as a well-
established diet score has been associated with a lower risk of
developing CKD and a rapid eGFR decline [4,8e12]. Khatri et al. [8]
found that greater adherence to Mediterranean diet was associated
with a reduced incidence of CKD and eGFR decline in community-
based cohort of 3298 participants with age >40 years. Hu et al. [10]
observed the same association in 12 155 participants aged 45e64
yeas over a median follow-up of 24 years. Our study shows that the
magnitude of the associations of the MDS with incident CKD and
eGFR decline was relatively consistent with other studies [8,10],
although we must mention that the association of tertiles of MDS
with incident CKD was reduced to borderline significance after full
adjustment. Since the follow-up time of our study was relatively
short, it had relatively limited power for analysis of incident CKD.
However, even with this limitation, the LLDS was still significantly
associated with a lower risk of incident CKD. Other types of dietary
pattern like the Western-style diet, characterized by highly pro-
cessed and refined foods and high contents of excessive sugar, salt,
and saturated and trans-fatty acids, have been associated with a
higher risk of CKD and impaired kidney function [31e33]. In the
Nurses’ Health Study of over 3000 elderly women, higher con-
sumption of animal fat and two or more servings per week of red
meat were found be associated with an increased risk of micro-
albuminuria [34]. Moreover, strong adherence to the Western di-
etary pattern was reported to be associated with a higher risk of
microalbuminuria and rapid kidney function decline in the same
cohort [35]. The LLDS integrates current evidence that emphasizes
high intake of plant-based foods, unsaturated fat and unsweetened
products, and low intake of processed foods, saturated fat, and
sweetened products. Our study adds to currently available data that
adhering to the contemporary, fully food-based LLDS is associated
with a lower risk of incident CKD and
20% GFR decline in the large
general population-based cohort study.
Of note, the LLDS and the MDS are based on different theoretical
approaches to define a healthy diet, and also, the way of translating
food intake into the score is different. As to the latter, each food
component of LLDS is categorized into quintiles and awarded 0 to 4
points. The components of MDS are scored relative to the median
intake and awarded 0 or 1 point. Since each component of MDS is
categorized into two groups, participants within the same group
have a more diverse intake than when the component is catego-
rized into five groups. Therefore, the scoring method of the LLDS is
sensitive to smaller differences between people. Although a direct
comparison of the LLDS and the MDS may not be warranted, our
finding may suggest stronger associations of LLDS with kidney
outcomes than of the MDS. This might be attributed to better res-
olution, as explained above, and/or the additional ranking of sugar-
sweetened beverages, cooking fats, tea, and coffee intake in LLDS.
High intakes of saturated fat and added sugar have been proven to
be associated with worse kidney outcomes [14,32,33]. Coffee intake
is associated with a decreased risk of the development of CKD [36].
Q. Cai, L.H. Dekker, P.C. Vinke et al. Clinical Nutrition 40 (2021) 5099e5105

Table 4
Associations of MDS with incident CKD and eGFR decline
20% by logistic regression analyses.

Tertiles of MDS Continuous MDS

OR (95% CI) OR (95% CI) per SD increase

T1 (0e3) T2 (4e5) T3 (6e9) P for trend P value

Incident CKD
Model 1 1.00 0.87 (0.78e0.97) 0.78 (0.69e0.88) <0.001 0.90 (0.86e0.94) <0.001
Model 2 1.00 0.85 (0.76e0.95) 0.75 (0.66e0.86) <0.001 0.89 (0.84e0.93) <0.001
Model 3 1.00 0.90 (0.79e1.02) 0.88 (0.76e1.01) 0.071 0.94 (0.89e0.99) 0.036
eGFR decline
20%
Model 1 1.00 0.96 (0.91e1.01) 0.93 (0.87e0.99) 0.032 0.97 (0.94e0.99) 0.004
Model 2 1.00 0.95 (0.90e1.01) 0.92 (0.86e0.99) 0.018 0.96 (0.94e0.99) 0.002
Model 3 1.00 0.95 (0.90e1.01) 0.92 (0.86e0.98) 0.009 0.96 (0.93e0.98) <0.001

Model 1. Adjusted for age and sex.

Model 2. Model 1 plus physical activity, smoking status, total energy intake, total alcohol intake, and education level.
Model 3. Model 2 plus baseline eGFR, BMI, diabetes, hypertension, and cardiovascular disease.

Whether tea consumption is associated with kidney health is not
clear, as it might be depending on the types of tea [37].
Strengths of this study include the large sample size and the use
of a food-based diet score based on solid contemporary scientific
evidence. At the same time, some limitations need to be noted.
First, our FFQ was self-administered, and some participants had to
be excluded due to unreliable dietary data. We evaluated diet only
at baseline, so we cannot exclude that participants might change
their diets over time. Second, misclassification of positive and
negative food groups might exist. For example, our FFQ does not
distinguish between whole grain and refined cereal products,
upon which we decided to consider bread intake a proxy for
whole-grain cereal products, since most bread consumed in the
Netherlands is whole wheat bread. Third, the definition of CKD
according to KDIGO guidelines is a persistent abnormality in kid-
ney structure or function (GFR lower than 60 mL/min per 1.73 m2
or albuminuria
30 mg per 24 h) for 3 months or longer [38]. We
only had one assessment of eGFR to estimate kidney function,
therefore, we could not evaluate kidney function over time.
Furthermore, we could not include albuminuria in our definition of
CKD because of the unavailable albuminuria information at the
second assessment, which may underestimate incident CKD.
Future studies can investigate the associations between the food-
based diet quality score assessed by LLDS and other biomarkers of
kidney function decline, such as cystatin C, urea nitrogen and FGF-
23. Future studies are needed to confirm the association of the
LLDS with incident CKD in other populations, and prospective
studies are needed to investigate whether adherence to LLDS may
preserve kidney function.
5. Conclusion
In conclusion, adherence to the contemporary, food-based diet
quality score (LLDS) was associated with a decreased risk of inci-
dent CKD and eGFR decline independent of known and potential
confounding risk factors in the general population. The LLDS as a
healthy diet score reflecting adherence to the 2015 Dutch Dietary
Guidelines can be a useful tool to evaluate overall diet quality and
provide empirical validation for the applicability of these guide-
lines for the prevention of CKD in the general population.
Funding statement
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Author contributions
QC, LHD, MHB, and GJN designed the study; QC and LHD
analyzed the data; QC, LHD, PCV, EC, SJLB, MHB, and GJN inter-
preted the results; QC made the figures; QC draft the manuscript;
LHD, PCV, EC, SJLB, MHB, and GJN revised the paper; all authors
approved the final version of the manuscript.
Conflict of interest
The authors of this manuscript have no conflicts of interest.
Acknowledgments
The authors wish to acknowledge the services of the Lifelines
Cohort Study, the contributing research centers delivering data to
Lifelines, and all the study participants.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.clnu.2021.07.033.
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