Nutritional Epidemiology and

Dietary Assessment for Patients

With Kidney Disease: A Primer
INTRODUCTION
• Nutritional epidemiology seeks to understand nutritional determinants of disease
in human populations.
• Links between diet and numerous chronic diseases, including chronic kidney
disease (CKD), have been discovered through epidemiologic investigations.
• With the rising global prevalence CKD, improved understanding of how diet
affects the risk and progression of CKD is imperative to inform care and
prevention recommendations.
Study Designs in Nutritional
Epidemiology
• Randomized controlled trials (RCTs) are considered the most rigorous design to
establish causality.
• Nutrition RCTs include controlled feeding studies, single nutrient or dietary
component studies, and dietary counseling studies
• The Modification of Diet in Renal Disease (MDRD) Study, investigated the effect of
restricting protein intake on glomerular filtration rate decline.
• Others have investigated the effect of dietary patterns or nutrients on kidney function
decline, blood pressure, anthropometrics, and biochemical derangements.
• Assessment of baseline intake or nutritional status and background diet (the dietary context
in which a food or nutrient is consumed) throughout the study duration may be useful to
interpret effects
• The expense and difficulty of sustaining adherence to dietary interventions limit the
duration and scale of RCTs in nutrition research
• Defining “adherence” a priori, and incorporating methods to assess it (e.g. direct
observation, return of unconsumed items, biomarker assessment, self-report), is essential to
monitor whether the intended intervention is delivered
• Ensuring palatability and acceptability of study diets (e.g. by previewing menus or tasting
study foods), and communicating clearly and regularly with participants throughout the
study duration, can promote retention and adherence.
• Incorporating a run-in period may be useful to evaluate adherence prior to randomization
and standardize baseline exposure
• Due to the long lead times and large sample sizes required to detect intervention effects on
hard endpoints, outcomes of nutrition RCTs are commonly intermediate markers of disease
risk
• Trials in kidney disease patients have used declines in glomerular filtration rate of varying
magnitudes or the onset of proteinuria as surrogate outcomes for the development of end-
stage kidney disease (ESKD) which may take years to occur.
• While sample size and study duration for RCTs investigating hard endpoints (ESKD,
death, cardiovascular events) could be minimized by enrolling participants with advanced
CKD, dietary interventions may not be equally effective at later versus early stages.
• Evidence regarding long-term effects of dietary exposures on hard endpoints have mostly originated
from observational study designs, predominantly prospective cohort studies, based on participants’
self reported dietary intakes.

• Cohorts of individuals without CKD at baseline, such as the Atherosclerosis Risk in Communities
(ARIC) study, have been used to study the association between diet and incident CKD

• In prospective cohort studies, assessment of dietary exposures before outcomes occur supports causal
inference. In contrast, cross-sectional studies such as the National Health and Nutrition Examination
Survey (NHANES) assess exposure and disease simultaneously and, therefore, yield weaker evidence
regarding causal effects of diet on disease but are useful to describe dietary intakes and quantify the
burden of insufficient or excess intakes in a population.

• In observational studies, exposure is selected by participants rather than assigned, and so the
influence of confounding factors on observed associations must be accounted for in statistical
analyses
Defining Dietary Exposures
• Diet is a complex exposure that varies in composition and quantity within
and between days and seasons. The covarying nature of dietary components
further complicates definition and statistical modeling of dietary exposures.
Conceptualizations of dietary exposures range from a reductionist focus on
nutrients to holistic characterizations of dietary patterns

• Guidelines for CKD management have emphasized dietary protein,

phosphorus, potassium, and sodium restrictions.

• However, nutrients are rarely consumed in isolation, except as supplements.

Instead, people consume foods, which contain various nutrient and non-
nutrient components that may affect health, and the bioavailability of these
components may differ depending on the food source and processing.
Dietary patterns may be defined a priori using predefined criteria (Table 2). For instance, higher adherence to a Mediterranean diet, Dietary
Approaches to Stop Hypertension (DASH)- style diet, and the Dietary Guidelines for Americans have been associated with lower risk of
incident CKD
• Alternatively, empirical approaches to defining dietary patterns use statistical
methods, such as factor or cluster analysis, that identify combinations of
foods consumed in a Journal Pre-proof population.

• Other holistic characterizations of dietary exposures may be defined based

on nutrient and food sources or their effects on hypothesized mediators of
disease risk
 Diet Assessment
Methods

Several methods are available to assess

dietary intakes (Table 3).
We broadly classify these methods as
traditional (self-report) and novel approaches.
Each method offers strengths and limitations
to consider when selecting the optimal
assessment for a given population, study
design, and exposure of interest
Traditional
Approaches
Food frequency questionnaires. Food frequency questionnaires (FFQs) query
habitual intake over a specified time period using a fixed list of foods, beverages,
and possibly nutritional supplements.

Food records. Food records, or food diaries, require respondents to log dietary
intakes in realtime over a specified time period, usually 3 to 7 days. Weighted food
records are regarded as the “gold standard” quantitative self-reported diet
assessment method and are used to validate other diet assessment methods. KDOQI
guidelines recommend use of 3 day food records to assess dietary intakes in clinical
practice.

24-Hour Dietary Recalls. A 24-hour dietary recall queries intake over the past day,
either midnight to midnight or the 24-hour period immediately preceding the recall.

Diet screeners. Screeners, or checklists, query intake of a select few items or eating
behaviors (e.g. sodium 56 or fruit and vegetable57 intake). The lack of detail and
susceptibility to systematic error limits their utility as a standalone diet assessment
method for research studies.
 Novel
Approaches
• Image-assisted dietary assessment. Image assisted dietary assessments
supplement or replace traditional self-report methods with photos or
videos of eating episodes in order to improve objectivity and avoid
reliance on memory.

• Wearable technologies. Wearable technologies offer the ability to

passively detect eating events in real-time by monitoring chewing,
swallowing, or jaw movements or by monitoring arm gestures associated
with eating.

• Retail sales and purchasing data. Market research companies collect

point-of-sale data from food retailers, as well as individual- and
household-level purchasing data using barcode scanning
• Dietary intake biomarkers. Dietary intake biomarkers enable
objective measurement of intake based on concentrations of
compounds measured in a biospecimen, commonly urine or
blood

• Only four recovery biomarkers have been identified: 24-hour

urinary nitrogen, reflecting protein intake; 24-hour urinary
potassium and sodium, reflecting intakes of these minerals; and
doubly-labeled water, a measure of energy expenditure that is
interpreted as a marker of energy intake in weight-stable
individuals

• Finally, most nutritional biomarkers have not been validated in

patients with CKD.78 Alternative markers or methods may be
needed when urinary output is altered or to account for water
soluble solute removal in dialysate
 Summary of Dietary Assessments

Errors associated with self-reported diet, their impacts on associations

with outcomes, and strategies to reduce them are well researched. While
novel dietary assessment approaches reduce some of these errors, they
have not yet replaced traditional methods. Combining self-report with
novel assessments may more comprehensively and accurately ascertain
dietary intakes.
Sources of Error
Measurement Error: Random

True dietary intakes vary within people, day to day. The degree of
intraindividual variability differs by food and nutrient, with higher
variability for episodically consumed foods (e.g. organ meats) and
nutrients concentrated in few food sources (e.g. vitamin A). A single day’s
intake – even if recorded correctly – does not accurately represent an
individual’s usual dietary intake of most foods or nutrients
 Measurement Error:
Systematic
While repeating dietary assessments can
improve precision by reducing random
measurement error, it will not address
systematic misreporting of intakes. The
degree of misreporting varies for different
population groups, foods, and dietary
assessment tools. For instance, people may
overreport intakes of “healthy” foods and
underreport “unhealthy” foods to align with
social norms (social desirability and social
approval biases),
Food Composition
Databases
Whether dietary intakes are self reported
or observed, conversion to nutrients and
foods requires linkage to nutrient
databases. Misestimation of nutrient
contents may arise due to geographical,
seasonal, or other natural sources of
variation in the nutritional composition of
foods.
Statistical Modeling
 Energy Adjustment

A methodological consideration unique to nutritional epidemiology is whether and how to adjust

for energy intake.90,97–99 People consuming more energy generally consume greater absolute
amounts of nutrients, and energy intake itself may be associated with CKD. Associations between
absolute dietary intakes and CKD may, therefore, be confounded benergy intake. Thus,
epidemiological analyses of associations between dietary intake and CKD typically aim to
statistically isolate between-person variation in intakes due to energy intake from variation
explained by changes in dietary composition.

When energy balance is maintained, increasing intake of a

macronutrient or energycontaining food or beverage requires
Subsitusi decreasing intakes of others, and its biological effect may differ
depending on what it displaces in the diet
 Future directions

1. Dietary recommendations for chronic disease prevention and management have evolved from
single nutrient modifications to a more holistic food-based dietary pattern approach

2. Refinement and validation of novel dietary assessment methods in CKD populations,

including patients on dialysis, will yield more objective measurements of intake, while
automated versions of traditional methods offer the potential to assess diet more frequently,
and in more detail, than previously possible.

3. Advancements in “omics” profiling – of the genome, transcriptome, proteome, metabolome,

and gut microbiome – offer opportunities to investigate mechanisms by which diet affects
kidney health
 Future directions

4. Genetic and epigenetic variations affect metabolic responses to diet, and diet can alter gene
expression, contributing to interindividual transcriptomic, proteomic, and metabolomic
variation that may mediate diet-CKD associations

5. As gut microbiome disturbances may contribute to CKD disease progression and

complications, its modulation by diet may impact prognosis. Omics technologies are
increasingly applied to advance and diet research

6. Application of these advancements in new and existing studies, combined with more
traditional approaches to risk stratification based on sociodemographic factors, health status,
and disease stage, will yield evidence to form more personalized dietary recommendation.
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