Ultraprocessed food and chronic kidney disease - double trouble

Abstract

High energy intake combined with low physical activity generates positive energy balance, which, when maintained, favors obesity, a highly prevalent morbidity linked to development of non-communicable chronic diseases, including chronic kidney disease (CKD). Among many factors contributing to disproportionally high energy intakes and thereby to the obesity epidemic, the type and degree of food processing play an important role. Ultra-processed foods (UPF) are industrialized and quite often high-energy-dense products with added sugar, salt, unhealthy fats, and food additives formulated to be palatable or hyper-palatable. UPF can trigger an addictive eating behavior and is typically characterized by an increase energy intake. Furthermore, high consumption of UPF, a hallmark of Western diet, results in diets with poor quality. A high UPF intake is associated with higher risk for CKD. In addition, UPF consumption by patients with CKD is likely to predispose and/or to exacerbate uremic metabolic derangements, such as insulin resistance, metabolic acidosis, hypertension, dysbiosis, hyperkalemia, and hyperphosphatemia. Global sales of UPF per capita increased in all continents in the last decades. This is an important factor responsible for the nutrition transition, with home-made meals being replaced by ready-to-eat products. In this review, we discuss the potential risk of UPF in activating hedonic eating, and its main implications for health, especially for kidney health and metabolic complications of CKD. We also present various aspects of consequences of UPF on planetary health and discuss future directions for research to bring awareness of the harms of UPFs within the CKD scenario.

Full text

Clinical Kidney Journal, 2023, vol. 0, no. 0, 1–14
https:/doi.org/10.1093/ckj/sfad103
Advance Access Publication Date: 4 May 2023
CKJ Review
CKJ REVIEW
Ultraprocessed foods and chronic kidney disease –
double trouble
Carla Maria Avesani1, Lilian Cuppari2, Fabiana Baggio Nerbass3,
Bengt Lindholm1and Peter Stenvinkel1
1Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Technology and Intervention,
Karolinska Instituted, Stockholm, Sweden, 2Division of Nephrology and Nutrition Program, Federal University
of São Paulo and S¯
ao Paulo, Brazil and 3Pró-Rim Foundation, Joinville, Santa Catarina, Brazil
Correspondence to: Carla Maria Avesani; E-mail: Carla.Avesani@ki.se
ABSTRACT
High energy intake combined with low physical activity generates positive energy balance, which, when maintained,
favours obesity, a highly prevalent morbidity linked to development of non-communicable chronic diseases, including
chronic kidney disease (CKD). Among many factors contributing to disproportionately high energy intakes, and thereby
to the obesity epidemic, the type and degree of food processing play an important role. Ultraprocessed foods (UPFs) are
industrialized and quite often high-energy-dense products with added sugar, salt, unhealthy fats and food additives
formulated to be palatable or hyperpalatable. UPFs can trigger an addictive eating behaviour and is typically
characterized by an increase in energy intake. Furthermore, high consumption of UPFs, a hallmark of a Western diet,
results in diets with poor quality. A high UPF intake is associated with higher risk for CKD. In addition, UPF consumption
by patients with CKD is likely to predispose and/or to exacerbate uraemic metabolic derangements, such as insulin
resistance, metabolic acidosis, hypertension, dysbiosis, hyperkalaemia and hyperphosphatemia. Global sales of UPFs per
capita increased in all continents in recent decades. This is an important factor responsible for the nutrition transition,
with home-made meals being replaced by ready-to-eat products. In this review we discuss the potential risk of UPFs in
activating hedonic eating and their main implications for health, especially for kidney health and metabolic
complications of CKD. We also present various aspects of consequences of UPFs on planetary health and discuss future
directions for research to bring awareness of the harms of UPFs within the CKD scenario.
LAY SUMMARY
When the diet we eat has more calories than the energy spent by the body, obesity may develop. Obesity increases
the risk of developing chronic kidney disease (CKD). Ultraprocessed foods (UPFs) are among the products that can
increase energy intake. UPFs include industrialized foods such as carbonated soft drinks, candies, ice cream,
mass-produced packaged breads and buns, margarines and other ready-to-eat foods. In some UPFs, sugar is replaced
for non-caloric articial sweeteners, which may not add as many calories, but are still unhealthy. For individuals with
CKD, a diet with large amounts of UPFs can trigger or worsen blood pressure and increase blood concentrations of
glucose, potassium and phosphate. Therefore we recommend that patients with CKD avoid or reduce the use of UPFs
in their diet and prefer home-made meals.
Received: 30.12.2022; Editorial decision: 30.3.2023
© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA. This is an Open Access article distributed under the terms of the Creative
Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution,
and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
1
Downloaded from https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfad103/7152602 by guest on 07 June 2023

2C. M. Avesani et al.
Keywords: chronic kidney disease, high energy intake, non-communicable diseases, ultraprocessed food
INTRODUCTION
In the long past, our foraging ancestors had to rely on hunting
and gathering to nd food and full the body’s needs for energy
and nutrients. This triggered metabolic adaptations to save en-
ergy in the form of adipose tissue for the sometimes long pe-
riods without food [1]. As the food supply became more pre-
dictable and more easily available, energy intake increased, and
this metabolic adaptation became less needed; however, the ac-
quired ability of the body to save a surplus of calories from the
diet in the form of adipose tissue remains [1]. Concomitantly,
the physical activity level has decreased substantially, with the
lifestyle of modern civilization creating a condition of positive
energy balance that favours the accumulation of fat and the
development of obesity [1]. Obesity is highly present, and its
prevalence has increased substantially in the past 40 years. In
2010, obesity [body mass index (BMI) >30 kg/m2] was present in
11.4% of adults worldwide while the estimated prevalence for
2025 is 16.1%, with an expected increase to 17.5% by 2030 [2].
This increase in obesity prevalence has an important impact on
the incidence of non-communicable diseases (NCDs), including
chronic kidney disease (CKD).
Obesity has been linked to the development of CKD in epi-
demiological studies as well as in experimental and observa-
tional studies and in clinical trials. Systematic reviews show that
obesity is associated with an increased risk of proteinuria, CKD
and end-stage kidney disease (ESKD) in persons with comorbidi-
ties predisposing to CKD and also in healthy individuals without
these comorbidities [3,4]. In contrast, weight loss is normally ac-
companied by a decrease in proteinuria, which may indicate a
protective effect on glomerular hyperltration [5,6]. Altogether,
it is plausible to assume that maintaining a positive energy bal-
ance from high caloric intake combined with low physical ac-
tivity is an important factor leading to obesity and to increasing
risk of developing CKD.
Among components leading to a positive energy balance, a
higher energy intake is a common nding [1]. As food became
more available with techniques that preserve foods, such as
cooking, salting, pickling, smoking and fermenting [7], energy in-
take increased substantially ≈2000 years ago. Industrial process-
ing started with canning and pasteurization in the 1800s and
with a rapid development in the 1900s of ready-to-eat packaged
meals aiming to serve soldiers in wars [7]. There is no doubt that
food processing has had a positive role in decreasing hunger by
delivering ready-to-eat food that can be stored for long periods
of time, but it has evolved to a degree where its benets to our
overall health can be argued [8].
So-called ultraprocessed foods (UPFs), a concept initially de-
veloped by the Brazilian nutrition researcher Carlos Monteiro at
the University of São Paulo, Brazil, are dened as products con-
taining ingredients exclusive to industrial processing using so-
phisticated equipment and technology for production (Table 1).
To produce UPFs, the food is subjected to chemical modications
with industrial techniques and the inclusion of additives that
can modify the texture, consistency, colour and taste, resulting
in products that are palatable or hyperpalatable, normally with
high energy density. In addition, UPFs can have added sugar,
oils, fructose, corn syrup, fats, salt, protein isolates and even
non-caloric articial sweeteners to replace sugar. Another char-
acteristic of UPFs is sophisticated packaging and being relatively
safe from a microbiological perspective. Altogether, UPFs trigger
an addictive eating behaviour that is a reason of concern for
overall health [9]. UPFs have become more affordable in recent
decades and, as a result, sales have increased tremendously over
time [10–12]. In Sweden, a 142% increase in the consumption
of UPFs was observed between 1960 and 2010, with the greatest
increase observed after 1995 [13]. Similarly, global sales of UPFs
(kg) per capita increased in all continents from 2006 to 2019, with
the highest sales of UPFs observed in Australia and North Amer-
ica and the lowest in South and Southeast Asia [12]. Of note,
the increase in UPFs was followed by a decrease in minimally
processed foods [12,13]. This change points to the consumption
of UPFs as a pivotal factor in the nutrition transition, with a
shift from traditional local diets to a Western dietary pattern
containing energy-dense food with increased sodium, saturated
fat, sugar, animal-sourced foods, rened carbohydrates and
non-caloric articial sweeteners that may not add calories, but
are still unhealthy, and relying on heavy industrial machinery
and processing [12]. Therefore, it is not surprising that the con-
sumption of UPFs is directly associated with an increase in the
prevalence of obesity and of other NCDs such as cardiovascular
disease (CVD), type 2 diabetes mellitus (T2DM), hypertension,
cancer, dementia, depression, CKD and non-alcoholic liver
disease [14–22]. Furthermore, hypothetically, the consumption
of UPFs by CKD patients can also be harmful by predisposing
and/or exacerbating metabolic derangements present in CKD.
In this review, we call attention to the potential harms of
a high intake of UPFs for the development of CKD and its
sequalae and the potential risks of UPFs further worsening
metabolic complications in CKD, such as insulin resistance, hy-
perkalaemia, hyperphosphatemia, metabolic acidosis, dyslipi-
daemia and dysbiosis. Despite the increasing consumption of
UPFs and increased evidence of their potential harmful effects
on health, their role in CKD has not yet been included in guide-
lines dedicated to the treatment of CKD. This review aims to
bring awareness of the harms of UPF consumption and the need
to consider UPFs in the agenda of future studies and guidelines
for CKD.
ENERGY HOMEOSTASIS CONTROL: INFLUENCE
OF UPFS IN ACTIVATING HEDONIC EATING
In a simplistic way, the energy balance of an individual is based
on the assumption that the energy intake must be similar to en-
ergy expenditure [1]. This theory is well accepted, but different
factors interfere in this balance, including the neuro-endocrine
regulation system. One important nding is that increased adi-
posity caused by failure to maintain stable body weight due to
high energy intake with concomitant low energy expenditure
could be the result of individuals overcoming the natural set
points of neuro-endocrine regulation, shifting the energy equi-
librium and making body weight maintenance more difcult [1].
In this regard, high fat and high sugar foods that are charac-
teristic of UPFs, activate mesolimbic reward, gustatory and oral
somatosensory brain regions, contributing to overeating [23].
Based on pooled data from ve published studies that measured
energy intake rates across a sample of 327 foods, Forde et al.[24]
found that going from unprocessed (36 ±4 kcal/min) and pro-
cessed (54 ±4 kcal/min) foods to UPFs (69 ±3 kcal/min), the
Downloaded from https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfad103/7152602 by guest on 07 June 2023

UPF and CKD – double trouble 3
Table 1: The NOVA food classication system according to the degree of industrial processing [27].
NOVA food group Denition Examples
(Group 1) Unprocessed or minimally processed foods Unprocessed: edible parts of plants, fungi, algae or from
animals after separation from nature or animals
Plant origin: fruits, seeds, leaves, stems, roots, tubers
Animal origin: eggs, milk, fat, meat
Minimally processed: minimal food processing, such as
pasteurization, freezing, placing in containers, vacuum
packing, non-alcoholic fermentation, no addition of sugar, fat,
salt or oils to the food
Tea, coffee, herbs, dried fruits, pasteurized milk, powdered
milk
(Group 2) Processed culinary ingredients Foods with industrial processes such as pressing, centrifuging,
rening or extracting. Used to prepare, season, and cook group
1 foods. May contain additives
Vegetable oils, butter, sugar, honey, syrup, starches; vegetable
oils with added antioxidants; salt mined or from seawater and
table salt with added drying agents
(Group 3) Processed foods Products made by adding salt, oil, sugar or other group 2
ingredients to group 1 foods. Uses preservation methods such
as canning and bottling, and in the case of breads and cheeses,
using non-alcoholic fermentation. May contain additives
Canned or bottled vegetables and legumes; salted or sugared
nuts and seeds; salted, dried, cured or smoked meats and sh;
canned sh; fruit in syrup; freshly made unpackaged breads
and cheeses
(Group 4) UPFs Product with the use of ingredients exclusive to the industrial
processing with sophisticated equipment and technology
Foods pass by chemical modications with industrial
techniques; use of additives
Foods are palatable or hyperpalatable and sophisticated
packaging with added sugar, oils or fats or salt, with high
fructose corn syrup, interesteried oils and protein isolates
Carbonated soft drinks; sweet or savoury packaged snacks;
chocolate, candies; ice-cream; mass-produced packaged
breads and buns; margarines and other spreads; cookies
(biscuits), pastries, cakes and cake mixes; breakfast ‘cereals’
‘Energy’ bars; ‘energy’ drinks; milk drinks, ‘instant’ sauces
Foods are designed to be affordable, long shelf- life and
convenient (ready to consume)
Pies, pasta and pizza dishes; poultry and sh ‘nuggets’,
sausages, peanut butter, hamburgers, powdered and packaged
‘instant’ soups, noodles and desserts. Infant formulas,
follow-on milks, replacement shakes and powders
Downloaded from https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfad103/7152602 by guest on 07 June 2023

4C. M. Avesani et al.
average energy intake rate increases signicantly [24]. In addi-
tion, an investigation that analysed 98 ready-to-eat foods found
that the higher the degree of industrial food processing, the
higher the glycaemic response and the lower its satiety poten-
tial [25]. These ndings are aligned with the discovery that in
addition to the ‘metabolic brain’, in which regulation of energy
intake is carried out by homeostatic mechanisms (glucostatic,
lipostatic and others), humans developed a ‘hedonic brain’, re-
sponsible for the motivational control of food intake, with a
complex reward system involving expression of opioid recep-
tors, cannabinoid receptors type 1 and several neurotransmit-
ters such as dopamine and serotonin, further inuencing ap-
petite and energy intake according to the palatability of foods
and the pleasure sensation [1]. Therefore UPFs are a potential
contributor to obesity by inducing hedonic eating through over-
riding the homeostatic control of food intake [26].
AN OVERVIEW OF UPFsAND THEIR MAIN
IMPLICATIONS FOR HEALTH
The term UPF was created for the new classication of foods
called NOVA that is based on the nature, extent and purposes
of the industrial processes that foods undergo [27]. These indus-
trial processes involve sophisticated techniques such as extru-
sion, moulding and pre-frying, with inclusion of articial sweet-
eners and additives to add colour, enhance avour, change food
consistency and increase shelf life [27]. All those procedures are
possible only with high-tech industrial machinery [27]. UPFs are
packed with synthetic materials and the nal product is palat-
able or highly palatable and can create an addictive eating pat-
tern [9]. Therefore the food processing itself may not be the prob-
lem, since most food consumed today has had some degree of
processing that shifts the food so that it no longer resembles
the form of the original food [27]. The NOVA food classication
system [27] is summarized in Table 1. Other food classication
systems are discussed in detail elsewhere [27]. For the current
review, the NOVA classication system will be described in more
detail since it has been the most used in epidemiological studies.
The main harm that UPFs represent to health is that due
to its poor nutritional value, the increase in the proportion of
UPFs in the diet is associated with a decrease in dietary qual-
ity indexes and to lower adherence to a healthy dietary pat-
tern, such as the Mediterranean diet [16]. This means that the
higher the proportion of UPFs, the worse the dietary quality [17,
28,29], even among pesco-vegetarians, vegetarians and vegans
that replace regular milk and meat for plant-based drinks and
textured soy protein foods, respectively [30]. The assessment of
UPF intake in the diet varies depending on how it is expressed,
e.g. as a percentage of total energy intake (TEI), as grams/day or
grams/kg/day or as a percentage of total food weight in the diet.
Other variables contributing to variations of UPFs in the diet in-
clude the geographical region, age group, social and educational
inequalities and, to a lower extent, gender [28]. In a systematic
review of studies from 21 countries estimating the UPF intake
as a proportion of the TEI using the NOVA classication, it was
found that the highest percentage of UPF intake was from the
USA and UK (≈50%) and the lowest was from Italy and Portugal
(≈10%) [28]. A similar nding was observed in studies from Eu-
ropean countries, where the UK and Germany had the highest
average household availability of UPFs, while Portugal and Italy
had the lowest [31]. Regarding age group, the percentage of UPF
intake from the TEI is higher in children and teenagers, since
UPFs are served in school cafeterias [28]. A higher UPF intake
was observed in young adults as compared with older adults,
a result that is believed to reect lifestyle patterns, such as the
habit of eating out, which is associated with higher UPF intake
[28]. Other factors shown to inuence UPF consumption are so-
cial and economic inequality, lower education level and unem-
ployment, which may lead to a preference for more affordable
and less nutritious foods, such as UPFs [28].
The most consumed UPFs are in general baked goods, dairy
products, reconstituted meat products, sugary products and
sugar-sweetened beverages [14,17,28,31]. As plant-based UPFs
and substitutes for meat and dairy products may be used by
vegans and vegetarians, UPFs could be a concern also among
those categories [32]. In fact, it was shown in a French cohort that
avoidance of animal-based food was associated with an increase
in UPF consumption among pesco-vegetarians, vegetarians and
vegans, with plant-based drinks, soy products, salty snacks and
biscuits being examples of commonly consumed UPFs [30]. In
addition, among the Adventist population, with many vegetari-
ans, those in the 90th percentile of UPF consumption (47.7% of
energy intake from UPFs) had a higher mortality risk than those
in the lower 10th percentile (12.1% of energy intake from UPFs),
while the same comparison between high and low animal-based
food intake (6.2% versus 0% of dietary energy with meats, di-
ary and eggs from the 90th and 10th percentiles, respectively)
was not associated with a higher mortality risk [33]. These
recent ndings indicate that plant-based UPFs also require
attention.
Altogether, it is not surprising that in the past 10 years
a plethora of studies have showed a consistent nding—the
higher the consumption of UPFs, the higher the chances of de-
veloping NCDs [14–19,22]. Of note, a Brazilian ecological study
showed that people from areas offering more UPFs were at
higher risk of death from cardiovascular diseases as compared
with people from areas with fewer available UPFs [34]. The most
important factors leading to these associations are summarized
in Fig. 1. First, UPFs are considered less satiating foods than
minimally processed foods due to alteration of the food matrix
through fractioning and recombination of ingredients [35]. This
property of UPFs promotes hedonic eating and overrides home-
ostatic control of food intake, increases TEI and consequently
leads to obesity [26]. There is evidence showing that UPFs lead
to higher caloric intake and to obesity in an animal experimen-
tal study [36] and in a randomized clinical trial [37]. In rats fed a
cafeteria diet (comprised mostly by UPFs), an obesity phenotype
accompanied by impaired serum fatty acids was found, with sig-
nicantly higher proportions of total saturated fatty acids [36].
Furthermore, the cafeteria diet induced gut dysbiosis with in-
creased levels of bacteroidetes [36].
In a randomized clinical trial, Hall et al.[37] demonstrated
that when healthy individuals with normal body weight were
exposed to a UPF-based diet for 2 weeks, there was a signicant
increase in ad libitum energy intake with a consequent increase
in body weight and body fat as compared with when the same
individuals were exposed during the same period to a diet of un-
processed food [37]. In another study with a cohort comprised
of older individuals from Spain, it was shown that those with
higher UPF consumption (>3 servings/day) had almost twice the
odds of having short telomeres than the others with lower UPF
consumption [38]. Since telomere shortening is associated with
inammation and oxidative stress and with higher biological
age, this nding adds to the list of potential harms of UPFs to hu-
man health. Also of importance,the presence of non-caloric arti-
cial sweeteners in UPFs, such as saccharin and aspartame, has
been implicated in the development of glucose intolerance,cen-
tral obesity and poor glucose control through changes of com-
position and function of the gut microbiota [39].
Downloaded from https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfad103/7152602 by guest on 07 June 2023

UPF and CKD – double trouble 5
Figure 1: Plausible links between higher consumption of UPFs and higher risk of developing NCDs.
Higher UPF consumption is associated with lower dietary quality (rst square). A high consumption of UPFs results in overeating a diet with high density food, with
added sugar,salt, unhealthy fats, non-caloric articial sweeteners, food additives and contaminants and molecular alterationsof food components due food processing
such as heating. UPFs lead to an increase in factors that are detrimental for health (second square). The conditions and factors listed in the rst and second squares
lead to an increased risk for obesity and NCDs, such as hypertension, cardiovascular disease (CVD), non-alcoholic fat liver disease (NAFLD) and CKD (third square).
CKD: chronic kidney disease; NCD: non-communicable diseases; UPF: ultraprocessed food.
Beyond the nutritional features, the industrial processing
of UPFs includes browning, caramelization and other changes
caused by a chemical reaction between amino acids and reduc-
ing sugars at high temperatures, called the Maillard reaction.
This reaction, which is a key feature of cooking and also one of
the formulas to enhance avouring, leads to the generation of
high levels of neo-formed contaminants (e.g. acrylamide, furans,
heterocyclic amines and others) [40,41] that are considered po-
tentially carcinogenic, explaining the association between UPF
consumption and the increased risk of cancer [42]. Other prod-
ucts with carcinogenic properties used in UPFs include addi-
tives, such as sodium nitrite (used in processed meat), titanium
dioxide (food pigment banned in Europe) and bisphenol (used
in packing) [43]. Moreover, these contaminants and many other
food additives have been shown to negatively affect components
of the intestinal microbiota that may lead to a disruption of the
intestinal barrier with increased abdominal bacterial exposure
and systemic inammation [44,45].
CONSUMPTION OF UPF AND KIDNEY HEALTH
Recently published observational studies from cohorts of differ-
ent geographic regions (Table 2) consistently show a signicant
association between increased UPF intake and the risk of devel-
oping CKD or a more rapid kidney function decline,independent
of how UPF consumption was evaluated [22,46–51]. In general,
the higher risk for CKD was found with UPF intakes >30% TEI
(Table 2). Considering the consistency of these ndings, one
can hypothesize that limiting UPF intake can prevent CKD
development. Among the potential explanations behind these
associations are the effect of a high sodium diet in altering the
renal and vascular systems and by increasing oxidative stress
regardless of changes in blood pressure [52,53]. Moreover, in
animals with normal kidney function fed a high sodium diet,
there were increases in markers of oxidative stress in skeletal
muscle arterioles and vessels, blood pressure, protein excretion
and renal brosis and worsened kidney function [54]. Other
mechanisms could be that UPFs contain increased amounts of
advanced glycation end products (AGEs) [55]. AGEs and their
respective precursors are produced in food manufacturing
during high-temperature and dry cooking methods (frying,
baking, broiling) [55]. The kidneys are the major site for clear-
ance of AGEs and, when in excess, AGEs can promote damage
in kidney structures [55]. In rodents, exposure to diets with
AGEs led to injury in the glomerulus with albuminuria [56].
This condition can be worsened in animals with T2DM [45]. In
Downloaded from https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfad103/7152602 by guest on 07 June 2023

6C. M. Avesani et al.
Table 2: Observational studies showing the association between the intake of UPFs and CKD.
Author, year Aim Methods Main ndings Comments
Gu et al., 2022 [51] To evaluate the association between UPF intake
and risk of CKD in two large cohorts
Observational and longitudinal study
Cohort: two cohorts from China
(n=23 775) and UK (n=102 332)
UPF intake: obtained from validated FFQ
in the rst cohort and from 24-hour
dietary recall using the NOVA system.
UPF expressed as quartiles of
energy-adjusted UPF (g/1000 kcal)
CKD denition: eGFR <60 ml/min/1.73 m2
or albumin:creatinine ratio ≥30 mg/g or
having a diagnosis of CKD
After a median of 4 years (China) and
10 years (UK) of follow-up, the HR for
CKD adjusted for multiple cofounders
across the UPF quartiles was:
China cohort:
1 (reference); 1.24 (95% CI 0.89–1.72); 1.30
(95% CI 0.91–1.87); 1.58 (95% CI 1.07–2.34);
Pfor trend =.02.
UK cohort:
1 (reference); 1.14 (95% CI 1.00–1.31); 1.16
(95% CI 1.01–1.33); 1.25 (95% CI 1.09–1.43);
Pfor trend <.01
Pooled HRs show that per SD increase in
UPF consumption there is a 9% increase
in risk of CKD in the two cohorts
combined [HR 1.09 (95% CI 1.04–1.15),
P=.001]
Kityo and Lee,
2022 [49]
To evaluate the association between UPF intake
and the prevalence of CKD and the eGFR in the
general population
Observational cross-sectional cohort
study
Cohort: n=134 544 from Korea. Age:
40–68 years with plausible dietary records
UPF intake: assessed by FFQ using the
NOVA system classication. UPF
expressed as quartiles of percentage of
UPF from total food weight.
CKD denition: eGFR <60 ml/min/1.73 m2
Median UPF intake: 5.6% of food weight
The prevalence of CKD increased in
parallel with UPF intake increase (Pfor
trend =.003) (adjusted analysis for
confounding variables)
Every IQR increase of UPF was associated
with a 6% increase in the prevalence of
CKD [prevalence ratio 1.06 (CI 1.03–1.09)].
High glucose was associated with an
increase in UPF IQR. Analysis adjusted
for confounders
A low median UPF percentage of total
food intake was observed as compared
with other studies
A single measure of eGFR was used
The FFQ used was not designed to
evaluate UPF
Du et al., 2022 [48] To evaluate the association between UPF
consumption and development of CKD in the
general population
Observational and longitudinal study The mean of energy-adjusted servings of
UPF consumption in the four quartiles
were 3.6, 5.2, 6.2 and 8.4 servings/day
Downloaded from https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfad103/7152602 by guest on 07 June 2023

UPF and CKD – double trouble 7
Table 2: Continued
Author, year Aim Methods Main ndings Comments
Cohort: 14 679 adults from USA without
CKD at baseline followed for 24 years
UPF intake: assessed by FFQ at visits 1
and 3. The NOVA system was used to
classify UPFs. UPFs were expressed as
servings/day adjusted for energy intake.
Quartiles of energy adjusted UPF
servings/day were calculated
CKD denition: presence of at least one
of four criteria: eGFR <60 ml/min/1.73 m2
accompanied by 25% eGFR decline;
CKD-related hospitalization; death
involving CKD; kidney failure with KRT
The highest quartile of UPF consumption
had a 24% higher risk [HR 1.24 (95% CI
1.15–1.35)] of developing CKD compared
with those in the lowest quartile
There was an approximately linear
relationship between UPF intake and the
risk of CKD
By substituting one serving of UPFs with
minimally processed foods, there was a
6% lower risk of CKD [HR 0.94 (95% CI
0.93–0.96), P<.001]
Montero-Salazar et al.,
2022 [50]
To evaluate the association between
dietary quality index and kidney function
in older adults
Cohort: 1312 older adults (≥60 years of
age) from Spain followed up to 6 years
Kidney function decline denition:
increase in SCr or decrease in eGFR
beyond changes expected for age
Food intake: assessed by food history.
Dietary quality index was categorized
based on Nutri-score. The higher the
Nutri-score score, the lower the dietary
quality.
Observational and longitudinal study
using a cohort of older adults
Each 10-point increase in the Nutri-score
dietary index was associated with odds
for a decrease in kidney function by 27%
(CI 6–52). Analysis adjusted for
confounding variables
This study does not assess the
consumption of UPF per se, but the higher
Nutri-score index was characterized by
containing least healthy foods and more
UPFs
Cai et al., 2022 [22] To evaluate the association between UPF
consumption and risk of kidney function
decline in the general population
Observational and longitudinal study
with a mean follow-up of 3.6 years
Cohort: 78 346 adults from the
Netherlands with normal renal function
and plausible dietary records
UPF consumption in the diet was
37.7 ±12.3%
The Mediterranean diet score decreased
as quartiles of UPF% increased
The FFQ used was not designed to
evaluate UPF
UPF intake: assessed from FFQ using the
NOVA classication system. UPF
expressed as percentage of total diet
weight in grams. Sex-specic quartiles of
UPF (% of total diet weight) were
calculated
In the follow-up analysis, participants in
the highest quartile of UPF% had a higher
risk of incident CKD or 30% eGFR decline
as compared with those in the lowest
UPF% quartile [OR 1.27% (95% CI
1.09–1.47), P=.003]
Mediterranean diet score was used to
evaluate the dietary quality
Participants in the highest UPF% had a
more rapid eGFR decline compared with
those in the lower quartile [β=−0.17
(95% CI −0.23 to −0.11), P<.011]
Analysis adjusted for confounding
variables
Downloaded from https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfad103/7152602 by guest on 07 June 2023

8C. M. Avesani et al.
Table 2: continued
Author, year Aim Methods Main ndings Comments
Osté et al., 2022 [47] To study the association between UPF
consumption and all-cause mortality in
KTR
Observational longitudinal study in adult
KTRs that were followed for a median of
5.7 years after transplantation for
all-cause mortality
Cohort: 632 KTRs from the Netherlands
with functioning graft after 1 year.
Patients with diabetes or history of
diabetes at baseline were not included
UPF intake: assessed from FFQ using the
NOVA classication system. UPF
expressed as a percentage of total diet
weight in grams
Sex-specic tertiles of UPF (% total diet
weight) were calculated
Primary outcome: all-cause
mortalitySecondary outcomes:
death-censored graft failure, renal
function decline (doubling serum
creatine in the follow-up) and PTDM
The mean UPF consumption in the diet
was 28% of total food weight/day
Adherence to the Mediterranean diet and
DASH diet was lower in the RTRs with
higher UPF consumption
UPF consumption was associated with
all-cause mortality [HR 2.13 (95% CI
1.46–3.10), P<.001]. Analysis adjusted for
confounding variablesUPF consumption
was associated with faster decline of
kidney function but not with
death-censored graft failure and PTDM
Rey-García et al., 2021 [46] To assess the association between UPF
consumption and kidney function
decline in the general population
Observational and longitudinal study in
individuals >60 years of age
Cohort: 1312 older adults from Spain
≥60 years of age followed up to 6.2 years
Food intake: assessed by food history.
UPF was identied using the NOVA
classication system. Sex-specic tertiles
of UPF expressed as % TEI and UPF
expressed in g/kg/day were calculated
A combined endpoint of kidney function
decline was considered when SCr
increased or eGFR decreased beyond that
expected for age from baseline to
follow-up
Participants with higher UPF
consumption at baseline had higher risk
of kidney function decline over time than
those with lower UPF consumption
UPF intake by %TEI:
Men: tertile 1, 8.6%; tertile 2, 18.7%; tertile
3, 33%
Women: tertile 1, 6.8%; tertile 2, 16.2%;
tertile 3, 29.8%
Analysis:
UPF intake by % TEI: tertile 3, OR 1.74
(95% CI 1.14–2.66), P=.023;
UPF intake by g/kg/day: tertile 3, OR 1.62
(95% CI 1.06–2.49), P=.043
This is the same cohort as that studied
by Montero-Salazar et al. 2022 [50]
The associations between UPF
consumption and kidney function
decline were stronger among patients
with diabetes and without obesity
CI: condence interval; eGFR: estimated glomerular ltration rate; FFQ: Food Frequency Questionnaire; HR: hazard ratio; KRT: kidney replacement therapy; KTR: kidney transplant recipient; OR: odds ratio; PTDM: post-transplant
diabetes; PR: prevalence ratio; SCr: serum creatinine.
Downloaded from https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfad103/7152602 by guest on 07 June 2023

UPF and CKD – double trouble 9
Figure 2: Intersection of a diet based on UPFs in driving complications related to CKD.
UPFs are characterized by poor dietary quality. This type of diet can further exacerbate comorbidities and contribute to the development of metabolic complications
already present in CKD. UPF: ultraprocessed food.
humans, consumption of diets with excessive amounts of AGEs
was associated with serum biomarkers of inammation, oxida-
tive stress, hyperglycaemia, hyperlipidaemia and endothelial
dysfunction [57]. In addition, in a randomized crossover trial,
10 healthy subjects were assigned to a 1-day high protein diet
with low AGEs content (10 cooked large chicken eggs) and to a
1-day diet with high AGEs content (industrialized fried chicken
nuggets). The study showed that renal perfusion and oxygen
consumption increased signicantly after the high AGEs diet.
Despite the short-term diet, this trial demonstrated that the
AGEs content of UPFs can modify kidney haemodynamics
[58]. Therefore, several pathophysiological explanations may
justify the higher predisposition of developing CKD or the faster
decline in kidney function in subjects with higher UPF intake.
When it comes to the intake of UPFs in patients with CKD, the
data are still scarce. In older adults (>60 years) on haemodialy-
sis (HD), the intake of UPFs (expressed as a percentage of TEI)
was signicantly higher than in non-CKD older adults [59]. Of
note, when further investigating the HD group, the UPF intake
(percentage of TEI) of the dialysis day was signicantly higher
than that of the weekend day and non-dialysis day. The long
hours away from home that makes it more difcult to eat home-
made meals may account for this. The dietary quality index
of the older adults on HD was also worse than that of older
non-CKD individuals [59]. In another study investigating kid-
ney recipients with stable graft function, it was observed that
the mean UPF consumption was equivalent to 28% of the to-
tal food weight/day and adherence to the Mediterranean diet
and Dietary Approaches to Stop Hypertension (DASH) diet was
lower in patients with higher UPF consumption. Furthermore,
UPF consumption was associated with a 2-fold increased mor-
tality risk [47]. One point that requires future investigation is the
use of plant-based products to replace animal protein in UPFs
and other foods. It may be that patients with CKD following low-
protein diets erroneously believe that plant-based dairy prod-
ucts and textured soy protein foods can be freely used because
of lower protein content.
The benets of reducing the UPF intake to levels similar to
that observed in countries with low UPF consumers was shown
in a study where the estimated dietary inadequacy for energy
density, free sugars and saturated fat and bre would decrease
from 9.5% to 76.8% depending on the nutrient and country in
question [60]. This extrapolation is an example of the potential
benets that lowering UPF intake can exert to prevent NCDs,in-
cluding CKD. In summary, the high consumption of UPFs in the
general population seems to be a determining factor leading to a
higher risk of CKD. In individuals with CKD, the consumption of
UPFs follows the high intake levels observed in the general pop-
ulation. The effects of UPFs in CKD require attention due to their
potential in worsening of uraemic metabolic complications.
UPFsAS DRIVERS OF METABOLIC
COMPLICATIONS IN CKD
Recent evidence suggests that UPF consumption can contribute
to metabolic acidosis, dysbiosis, hyperphosphatemia and hy-
perkalaemia (Fig. 2). Metabolic acidosis is a common complica-
tion of CKD [61] that can lead to bone demineralization, muscle
mass loss and CKD progression [62]. Due to the preponderance of
animal-sourced food components, including many of the UPFs,
the modern Western-type diet is considered H+-producing as
compared with base-producing plant-sourced diets [63]. In ad-
dition, proteins from animal sources contains sulphur amino
acids, such as methionine and cysteine, that when metabolized
yield sulphuric acid. The content of these amino acids is 2–5-fold
higher in meat and eggs than in grains and legumes. In contrast,
most fruits and vegetables have fewer sulphur-containing amino
acids and they contain organic salts (e.g. potassium citrate and
malate) that, when metabolized, release bicarbonate and thus
provide alkali to the body [63]. Therefore a preponderance of
UPFs in the diet mainly from processed meat may increase acid
retention in CKD. Furthermore, the additives present in UPFs,
such as salt (sodium chloride), can independently increase acid
load and lower bicarbonate, accounting for 50–100% of the di-
etary acid load [64]. Carbonated drinks containing carbonic acid
and those containing phosphoric acid, such as cola-based so-
das, have some of the highest levels of acidity among soft drinks.
Downloaded from https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfad103/7152602 by guest on 07 June 2023

10 C. M. Avesani et al.
Other widely used phosphate-based additives in UPFs, such as
calcium acid pyrophosphate used in processed meat and potato
products, are also a source of acids [65].
Another problem with high UPF intake is that it associates
with low intake of foods with a high bre content (fruits, veg-
etables, grains and whole cereals). The high intake of protein
and fat is harmful for the gut, leading to detrimental protein and
choline fermentation instead of benecial fermentation coming
from bre carbohydrates [66]. In addition, this type of diet aug-
ments the colonic transit time, which also has a negative impact
on colonic microbiome composition. Under this condition, there
is growth of proteolytic species (proteolytic bacteria), resulting
in increased generation and uptake of end products of bacte-
rial protein fermentation (ammonia, amines, thiols, phenols and
indoles) and to gut dysbiosis [67–69]. However, a recent study in
mice has raised the possibility that some of the uraemic tox-
ins generated by bacterial fermentation of amino acids, includ-
ing hydrogen sulphide, seem to have a physiological and poten-
tially benecial effect on the progression of CKD [70]. Moreover,
since the uraemic milieu can lead to gut dysbiosis by increasing
the inux of circulating urea and other toxins to the gut lumen,
the combination with poor bre intake can increase gut produc-
tion of uraemic toxins, such as p-cresyl sulphate, indoxyl sul-
phate and trimethylamine-N-oxide [68,69,71]. In HD patients,
increased adherence to an unhealthy plant-based diet contain-
ing UPFs such as processed fruit juices, sugar-sweetened bev-
erages, rened grains, chips and crisps and sweets and deserts
was associated with an increase in free and total indoxyl sul-
phate. Moreover, an increase in the intake of these UPFs was
linked to higher circulating concentrations of indoxyl sulphate
and p-cresyl sulphate [72], suggesting an indirect effect of UPFs
in worsening gut microbiotic uraemic toxin production.
Phosphate-based and potassium-based additives present in
UPFs may worsen hyperphosphatemia and hyperkalaemia [73,
74]. Compared with similar food items without additives, phos-
phorus and potassium content is ≈70–100% higher in food
that contain additives [75–77]. In addition, the intestinal ab-
sorption of inorganic phosphorus and potassium additives is
close to 100%, compared with plant- (20–50%) and animal-based
sources (40–60%) [78]. So far, studies evaluating the association
between higher intake of UPFs and hyperphosphatemia and hy-
perkalaemia are lacking in CKD. Limiting the consumption of
UPFs may be especially important in the large group of patients
with both T2DM and CKD, as part of a holistic approach for im-
proving management and outcomes in these patients [79,80].
SEEKING PLANETARY HEALTH: ANOTHER
REASON TO AVOID UPF
Adding to the harms of high UPF intake for overall and kidney
health, UPFs tend to be harmful for the environment [81]. The
food system, including all processes in the food chain, produc-
tion, processing, packing, distributing, consumption and recy-
cling, contributes to ≈30% of total greenhouse gas emissions [82],
the major risk factor for global warming and climate change [82].
The EAT-Lancet commission launched a healthy mainly plant-
based diet that is safe for the environment and for overall health
[83]. This type of diet relies on fresh, preferably locally produced
products (such as fruits, vegetables, whole grains and nuts); veg-
etable protein (from beans), with lower amounts of red meat,
eggs and dairy products [84]; and no use of UPFs. In addition,
the production of UPFs depends on a system that requires large
amounts of energy, land and water, with land degradation, bio-
diversity loss and plastics and metals pollution [84]. In other
words, the food chain of UPFs is highly unsustainable and leads
to a ‘lose–lose’ situation, meaning bad for the environment and
bad for human health [84]. A recent study by da Silva et al.
[85] showed that the environmental effects of the Brazilian diet
have increased over the past 3 decades along with increased ef-
fects from UPFs, indicating that dietary patterns in Brazil are be-
coming potentially more harmful to both human and planetary
health. Thus the negative effects of UPFs on planetary health
are another strong argument to diminish the consumption of
UPFs and the kidney care community needs to educate health-
care professionals, patients and the population at large about
the perils of UPFs [81]. As recently discussed by Lawrence [86],
the UPF concept challenges several traditionalnutrition research
and policy undertakings as well as the political economy of the
industrial food system.
CONCLUSIONS AND FUTURE DIRECTIONS
Excessive energy intake is a main factor driving the worldwide
epidemic of obesity, which in turn is linked to the increase of
NCDs, including CKD. A better understanding of the underlying
driving factors is needed to halt this unfortunate development.
Perhaps among the factors contributing to high energy intake,
the most important one is UPFs, which are energy dense foods
with low nutritional value. The increasing consumption of di-
ets with a high UPF content (often >30% of TEI), a hallmark of
the modern Western diet, reects global trends—supported by
industrial food production, processing and marketing—towards
hedonic dietary patterns replacing more healthy home-made di-
ets often based on locally produced food and beneting from the
use of traditional methods such as fermentation. This change is
leading to diets with poor quality and increased amounts of food
additives that may be harmful for human and planetary health.
Tab le 3summarizes attractive and harmful factors of UPFs in
the diet. For a high-risk patient group like those with CKD, high
consumption of UPFs has the potential to further worsen the
metabolic risk factor prole and progression. We suggest the in-
clusion of statements regarding UPFs in dietary CKD guidelines
to guide healthcare professionals and patients [87]. The Brazil-
ian nutrition guidelines [88] and the 2021 dietary guidance to
improve cardiovascular health [89] are examples of how to em-
phasize the importance of advocating healthy dietary patterns
rather than recommendations based on advantages or restric-
tions of individual nutrients. Finally, there is a need for increased
public awareness regarding the potential perils of UPFs, and all
data regarding the human and planetary health concerns re-
lated to increased use of UPFs need to reach policymakers. We
suggest a trafc light food labelling system (green–yellow–red)
to be used in grocery stores so that the public, and especially
risk groups with NCDs, can make healthier food consumption
decisions, with the hope that this also may have an impact on
the food industry and pave the way for more sustainable and
healthier food production.
FUNDING
C.M.A. and P.S. received a grant from the Erasmus+fund-
ing programme of the European Union (ePlanet 2021-1-NL01-
KA220-HED-000032029). C.M.A. acknowledges the Stig and Gun-
borg Westman Foundation for Research and the Martin Rind
Foundation. L.C. receives a stipend from Conselho Nacional
de Desenvolvimento Cientíco e Tecnológico (302765/2017-
Downloaded from https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfad103/7152602 by guest on 07 June 2023

UPF and CKD – double trouble 11
Table 3: Main potential attractive and harmful factors concerning the consumption of UPFs.
Attractive factors Harmful factors
More affordable
Relatively safe
Long shelf-life
Palatable or highly palatable
Ease of use: ready to eat or easily prepared foods
Attractive marketing and packaging
Low in nutritional quality
High energy density
High in added sugar, salt, fat, articial sweeteners and additives
Can trigger addictive eating pattern
Lead to overeating
Increased risk of obesity and development of NCDs
Globalized diet that is replacing the culturally based home-made meals
UPF production relies on food systems that are not sustainable for the planet
4). B.L. acknowledges support from Baxter Healthcare. P.S.
acknowledges support from the Center for Innovative Medicine,
Karolinska Institutet; the Stig and Gunborg Westman Founda-
tion for Research; the Heart and Lung Foundation; Njurfonden
and the Swedish Medical Research Council.
AUTHORS’ CONTRIBUTIONS
C.M.A., L.C. and F.B.N. were responsible for conception of the re-
view, drafting and/or revision of the manuscript and approval of
the nal version of the manuscript. B.L. and P.S. were responsi-
ble for drafting and/or revision of the manuscript and approval
of the nal version of the manuscript.
DATA AVAILABILITY STATEMENT
No new data were generated or analysed in support of this re-
search.
CONFLICT OF INTEREST STATEMENT
The authors declare no conicts of interest.
REFERENCES
1. Vettor R, Di Vincenzo A, Maffei P et al. Regulation of
energy intake and mechanisms of metabolic adapta-
tion or maladaptation after caloric restriction. Rev En-
docr Metab Disord 2020;21:399–409. https://doi.org/10.1007/
s11154-020-09565-6
2. World Obesity Federation. World Obesity Atlas 2022. London:
Ludgate House; 2022.
3. Garofalo C, Borrelli S, Minutolo R et al. A systematic re-
view and meta-analysis suggests obesity predicts onset of
chronic kidney disease in the general population. Kidney Int
2017;91:1224–35. https://doi.org/10.1016/j.kint.2016.12.013
4. Friedman AN, Kaplan LM, le Roux CW et al. Management of
obesity in adults with CKD. J Am Soc Nephrol 2021;32:777–90.
https://doi.org/10.1681/ASN.2020101472
5. Li K, Zou J, Ye Z et al. Effects of bariatric surgery on renal
function in obese patients: a systematic review and meta
analysis. PLoS One 2016;11:e0163907. https://doi.org/10.1371/
journal.pone.0163907
6. Afshinnia F, Wilt TJ, Duval S et al. Weight loss and pro-
teinuria: systematic review of clinical trials and compara-
tive cohorts. Nephrol Dial Transplant 2010;25:1173–83. https://
doi.org/10.1093/ndt/gfp640
7. Knorr D, Watzke H. Food processing at a crossroad. Front Nutr
2019;6:85. https://doi.org/10.3389/fnut.2019.00085
8. Dicken SJ, Batterham RL. Ultra-processed food: a
global problem requiring a global solution. Lancet Di-
abetes Endocrinol 2022;10:691–4. https://doi.org/10.1016/
S2213-8587(22)00248-0
9. Monteiro CA, Cannon G, Levy RB et al. Ultra-processed foods:
what they are and how to identify them. Public Health Nutr
2019;22:936–41. https://doi.org/10.1017/S1368980018003762
10. Maia EG, Dos Passos CM, Levy RB et al. What to expect from
the price of healthy and unhealthy foods over time? The
case from Brazil. Public Health Nutr 2020;23:579–88. https://
doi.org/10.1017/S1368980019003586
11. Moodie R, Bennett E, Kwong EJL et al. Ultra-processed
prots: the political economy of countering the global
spread of ultra-processed foods – a synthesis review on the
market and political practices of transnational food corpo-
rations and strategic public health responses. Int J Health Pol-
icy Manag 2021;10:968–82. https://www.ijhpm.com/article_
4050.html
12. Baker P, Machado P, Santos T et al. Ultra-processed foods
and the nutrition transition: global, regional and national
trends, food systems transformations and political econ-
omy drivers. Obes Rev 2020;21:e13126. https://doi.org/10.
1111/obr.13126
13. Juul F, Hemmingsson E. Trends in consumption of ultra-
processed foods and obesity in Sweden between 1960 and
2010. Public Health Nutr 2015;18:3096–107. https://doi.org/10.
1017/S1368980015000506
14. Vandevijvere S, Jaacks LM, Monteiro CA et al. Global trends
in ultraprocessed food and drink product sales and their as-
sociation with adult body mass index trajectories. Obes Rev
2019;20:10–9. https://doi.org/10.1111/obr.12860
15. Lane MM, Davis JA, Beattie S et al. Ultraprocessed food and
chronic noncommunicable diseases: a systematic review
and meta-analysis of 43 observational studies. Obes Rev
2021;22:e13146. https://doi.org/10.1111/obr.13146
16. Dicken SJ, Batterham RL. The role of diet quality in medi-
ating the association between ultra-processed food intake,
obesity and health-related outcomes: a review of prospec-
tive cohort studies. Nutrients 2021;14:23. https://doi.org/10.
3390/nu14010023
17. Srour B, Fezeu LK, Kesse-Guyot E et al. Ultra-processed food
intake and risk of cardiovascular disease: prospectivecohort
study (NutriNet-Santé). BMJ 2019;365:l1451. https://doi.org/
10.1136/bmj.l1451
18. Fiolet T, Srour B, Sellem L et al. Consumption of
ultra-processed foods and cancer risk: results from
Downloaded from https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfad103/7152602 by guest on 07 June 2023

12 C. M. Avesani et al.
NutriNet-Santé prospective cohort. BMJ 2018;360:k322.
https://doi.org/10.1136/bmj.k322
19. Cai Q, Duan MJ, Dekker LH et al. Ultra-processed
food consumption and kidney function decline in a
population-based cohort in the Netherlands. Am J Clin Nutr
2022;116:263–73. https://doi.org/10.1093/ajcn/nqac073
20. Gomes Gonçalves N, Vidal Ferreira N, Khandpur N et al.
Association between consumption of ultraprocessed
foods and cognitive decline. JAMA Neurol 2023;80:142–
50. https://jamanetwork.com/journals/jamaneurology/
article-abstract/2799140
21. Gómez-Donoso C, Sánchez-Villegas A, Martínez-González
MA et al. Ultra-processed food consumption and the inci-
dence of depression in a Mediterranean cohort: the SUN
Project. Eur J Nutr 2020;59:1093–103. https://doi.org/10.1007/
s00394-019-01970-1
22. Cai Q, Duan MJ, Dekker LH et al. Ultraprocessed
food consumption and kidney function decline in a
population-based cohort in the Netherlands. Am J Clin Nutr
2022;116:263–73. https://doi.org/10.1093/ajcn/nqac073
23. Stice E, Burger KS, Yokum S. Relative ability of fat and
sugar tastes to activate reward, gustatory, and somatosen-
sory regions. Am J Clin Nutr 2013;98:1377–84. https://doi.org/
10.3945/ajcn.113.069443
24. Forde CG, Mars M, de Graaf K. Ultra-processing or oral pro-
cessing? A role for energy density and eating rate in mod-
erating energy intake from processed foods. Curr Dev Nutr
2020;4:nzaa019. https://doi.org/10.1093/cdn/nzaa019
25. Fardet A. Minimally processed foods are more satiat-
ing and less hyperglycemic than ultra-processed foods: a
preliminary study with 98 ready-to-eat foods. Food Funct
2016;7:2338–46. https://doi.org/10.1039/C6FO00107F
26. Neumann NJ, Fasshauer M. Added avors: potential contrib-
utors to body weight gain and obesity? BMC Med 2022;20:417.
https://doi.org/10.1186/s12916-022-02619-3
27. Monteiro CA, Cannon G, Lawrence M et al. Ultra-processed
foods, diet quality, and health using the NOVA classication sys-
tem. Rome: Food and Agriculture Organization; 2019.
28. Marino M, Puppo F, Del Bo’ C et al. A systematic review
of worldwide consumption of ultra-processed foods: nd-
ings and criticisms. Nutrients 2021;13:2778. https://doi.org/
10.3390/nu13082778
29. Julia C, Martinez L, Allès B et al. Contribution of ultra-
processed foods in the diet of adults from the French
NutriNet-Santé study. Public Health Nutr 2018;21:27–37.
https://doi.org/10.1017/S1368980017001367
30. Gehring J, Touvier M, Baudry J et al. Consumption of ultra-
processed foods by pesco-vegetarians, vegetarians, and ve-
gans: associations with duration and age at diet initiation.
JNutr2021;151:120–31. https://doi.org/10.1093/jn/nxaa196
31. Monteiro CA, Moubarac JC, Levy RB et al. Household avail-
ability of ultra-processed foods and obesity in nineteen Eu-
ropean countries. Public Health Nutr 2018;21:18–26. https://
doi.org/10.1017/S1368980017001379
32. Orlich MJ, Jaceldo-Siegl K, Sabaté J et al. Patterns of food
consumption among vegetarians and non-vegetarians.
Br J Nutr 2014;112:1644–53. https://doi.org/10.1017/
S000711451400261X
33. Orlich MJ, Sabaté J, Mashchak A et al. Ultra-processed food
intake and animal-based food intake and mortality in the
Adventist Health Study-2. Am J Clin Nutr 2022;115:1589–601.
https://doi.org/10.1093/ajcn/nqac043
34. Victor A, Silva RCR, Silva NJ et al. Inuenceofun-
healthy food environment on premature cardiovascular dis-
ease mortality in Brazil: an ecologic approach. Am J Prev
Med 2023;64:285–92. https://doi.org/10.1016/j.amepre.2022.
09.018
35. Fardet A, Lakhssassi S, Briffaz A. Beyond nutrient-based food
indices: a data mining approach to search for a quantita-
tive holistic index reecting the degree of food process-
ing and including physicochemical properties. Food Funct
2018;9:561–72. https://doi.org/10.1039/C7FO01423F
36. de la Garza AL, Martínez-Tamez AM, Mellado-Negrete A et al.
Characterization of the cafeteria diet as simulation of the
human Western diet and its impact on the lipidomic pro-
le and gut microbiota in obese rats. Nutrients 2022;15:86.
https://doi.org/10.3390/nu15010086
37. Hall KD, Ayuketah A, Brychta R et al. Ultra-processed diets
cause excess calorie intake and weight gain: an inpatient
randomized controlled trial of ad libitum food intake. Cell
Metab 2019;30:67–77.e3. https://doi.org/10.1016/j.cmet.2019.
05.008
38. Alonso-Pedrero L, Ojeda-Rodríguez A, Martínez-González
MA et al. Ultra-processed food consumption and the risk of
short telomeres in an elderly population of the Seguimiento
Universidad de Navarra (SUN) Project. Am J Clin Nutr
2020;111:1259–66. https://doi.org/10.1093/ajcn/nqaa075
39. Suez J, Korem T, Zeevi D et al. Articial sweeteners induce
glucose intolerance by altering the gut microbiota. Nature
2014;514:181–6. https://doi.org/10.1038/nature13793
40. Birlouez-Aragon I, Morales F, Fogliano V et al. The health
and technological implications of a better control of neo-
formed contaminants by the food industry. Pathol Biol (Paris)
2010;58:232–8. https://doi.org/10.1016/j.patbio.2009.09.015
41. Mariotti MS, Granby K, Rozowski J et al. Furan: a critical
heat induced dietary contaminant. Food Funct 2013;4:1001–
15. https://doi.org/10.1039/c3fo30375f
42. Dybing E, Sanner T. Risk assessment of acrylamide in
foods. Toxicol Sci 2003;75:7–15.https://doi.org/10.1093/toxsci/
kfg165
43. World Health Organization International Agency for Re-
search on Cancer. IARC monographs on the evaluation of car-
cinogenic risks to humans. Volume 93. Carbon black, titanium
dioxide and talc. Geneva: World Health Organization Press;
2010.
44. Vissers E, Wellens J, Sabino J. Ultra-processed foods as a pos-
sible culprit for the rising prevalence of inammatory bowel
diseases. Front Med 2022;9:1058373. https://doi.org/10.3389/
fmed.2022.1058373
45. Snelson M, Tan SM, Clarke RE et al. Processed foods drive in-
testinal barrier permeability and microvascular diseases. Sci
Adv 2021;7:eabe4841. https://doi.org/10.1126/sciadv.abe4841
46. Rey-García J, Donat-Vargas C, Sandoval-Insausti H et al.
Ultra-processed food consumption is associated with renal
function decline in older adults: a prospective cohort study.
Nutrients 2021;13:428. https://doi.org/10.3390/nu13020428
47. Osté MCJ, Duan MJ, Gomes-Neto AW et al. Ultra-processed
foods and risk of all-cause mortality in renal transplant re-
cipients. Am J Clin Nutr 2022;115:1646–57. https://doi.org/10.
1093/ajcn/nqac053
48. Du S, Kim H, Crews DC et al. Association between ultra-
processed food consumption and risk of incident CKD: a
prospective cohort study. Am J Kidney Dis 2022;80:589–98.e1.
https://doi.org/10.1053/j.ajkd.2022.03.016
49. Kityo A, Lee SA. The intake of ultra-processed foods and
prevalence of chronic kidney disease: the Health Exami-
nees Study. Nutrients 2022;14:3548. https://doi.org/10.3390/
nu14173548
Downloaded from https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfad103/7152602 by guest on 07 June 2023

UPF and CKD – double trouble 13
50. Montero-Salazar H, Guallar-Castillón P, Banegas JR et al. Food
consumption based on the nutrient prole system under-
lying the Nutri-Score and renal function in older adults.
Clin Nutr 2022;41:1541–8. https://doi.org/10.1016/j.clnu.2022.
05.004
51. Gu Y, Li H, Ma H et al. Consumption of ultraprocessed food
and development of chronic kidney disease: the Tianjin
Chronic Low-Grade Systemic Inammation and Health and
UK Biobank Cohort Studies. Am J Clin Nutr 2023;117:373–82.
52. Nerbass FB, Calice-Silva V, Pecoits-Filho R. Sodium intake
and blood pressure in patients with chronic kidney disease:
a salty relationship. Blood Purif 2018;45:166–72. https://doi.
org/10.1159/000485154
53. He FJ, Tan M, Ma Y et al. Salt reduction to prevent hyper-
tension and cardiovascular disease: JACC state-of-the-art
review. J Am Coll Cardiol 2020;75:632–47. https://doi.org/10.
1016/j.jacc.2019.11.055
54. Kitiyakara C, Chabrashvili T, Chen Y et al. Salt intake, ox-
idative stress, and renal expression of NADPH oxidase and
superoxide dismutase. J Am Soc Nephrol 2003;14:2775–82.
https://doi.org/10.1097/01.ASN.0000092145.90389.65
55. Fotheringham AK, Gallo LA, Borg DJ et al. Advanced glyca-
tion end products (AGEs) and chronic kidney disease: does
the modern diet AGE the kidney? Nutrients 2022;14:2675.
https://doi.org/10.3390/nu14132675
56. Vlassara H, Striker LJ, Teichberg Set al. Advanced glyca-
tion end products induce glomerular sclerosis and albumin-
uria in normal rats. Proc. Natl Acad Sci USA 1994;91:11704–8.
https://doi.org/10.1073/pnas.91.24.11704
57. Chao PC, Huang CN, Hsu CC et al. Association of dietary
AGEs with circulating AGEs, glycated LDL, IL-1αand MCP-
1 levels in type 2 diabetic patients. Eur J Nutr 2010;49:429–34.
https://doi.org/10.1007/s00394-010-0101-3
58. Normand G, Lemoine S, Villien M et al. AGE content of a
protein load is responsible for renal performances: a pilot
study. Diabetes Care 2018;41:1292–4. https://doi.org/10.2337/
dc18-0131
59. Martins AM, Bello Moreira AS, Canella DS et al. Elderly
patients on hemodialysis have worse dietary quality and
higher consumption of ultraprocessed food than elderly
without chronic kidney disease. Nutrition 2017;41:73–9.
https://doi.org/10.1016/j.nut.2017.03.013
60. Martinez Steele E, Marrón Ponce JA, Cediel G et al. Potential
reductions in ultra-processed food consumption substan-
tially improve population cardiometabolic-related dietary
nutrient proles in eight countries. Nutr Metab Cardiovasc
Dis 2022;32:2739–50. https://doi.org/10.1016/j.numecd.2022.
08.018
61. Raphael KL, Zhang Y, Ying J et al. Prevalence of and risk fac-
tors for reduced serum bicarbonate in chronic kidney dis-
ease. Nephrology 2014;19:648–54. https://doi.org/10.1111/nep.
12315
62. Raphael KL. Metabolic acidosis in CKD: Core Curriculum
2019. Am J Kidney Dis 2019;74:263–75. https://doi.org/10.1053/
j.ajkd.2019.01.036
63. Remer T, Manz F. Potential renal acid load of foods and
its inuence on urine pH. J Am Diet Assoc 1995;95:791–7.
https://doi.org/10.1016/S0002-8223(95)00219-7
64. Frassetto LA, Morris RC, Sebastian A. Dietary sodium
chloride intake independently predicts the degree of
hyperchloremic metabolic acidosis in healthy humans con-
suming a net acid-producing diet. Am J Physiol Renal Phys-
iol 2007;293:F521–5. https://doi.org/10.1152/ajprenal.00048.
2007
65. Passey C. Reducing the dietary acid load: how a more al-
kaline diet benets patients with chronic kidney disease.
JRenNutr2017;27:151–60. https://doi.org/10.1053/j.jrn.2016.
11.006
66. Su G, Qin X, Yang C et al. Fiber intake and health in peo-
ple with chronic kidney disease. Clin Kidney J 2022;15:213–25.
https://doi.org/10.1093/ckj/sfab169
67. Andrade LSRC, Cuppari L. The cross-talk between the kidney
and the gut: implications for chronic kidney disease. Nutrire
2017;42:27.
68. Montemurno E, Cosola C, Dalno G et al. What would
you like to eat, Mr CKD Microbiota? Kidney Blood Press Res
2014;39:114–23. https://doi.org/10.1159/000355785
69. Mafra D, Borges N, Alvarenga L et al. Dietary compo-
nents that may inuence the disturbed gut microbiota in
chronic kidney disease. Nutrients 2019;11:496. https://doi.
org/10.3390/nu11030496
70. Lobel L, Cao YG, Fenn K et al. Diet posttranslationally mod-
ies the mouse gut microbial proteome to modulate renal
function. Science 2020;369:1518–24. https://doi.org/10.1126/
science.abb3763
71. Lau WL, Kalantar-Zadeh K, Vaziri ND. The gut as a
source of inammation in chronic kidney disease. Nephron
2015;130:92–8. https://doi.org/10.1159/000381990
72. Stanford J, Charlton K, Stefoska-Needham A et al. Associa-
tions among plant-based diet quality, uremic toxins, and gut
microbiota prole in adults undergoing hemodialysis ther-
apy. JRenNutr2021;31:177–88. https://doi.org/10.1053/j.jrn.
2020.07.008
73. Parpia AS, L’Abbé M, Goldstein M et al. The Impact of ad-
ditives on the phosphorus, potassium, and sodium con-
tent of commonly consumed meat, poultry, and sh prod-
ucts among patients with chronic kidney disease. JRenNutr
2018;28:83–90. https://doi.org/10.1053/j.jrn.2017.08.013
74. Picard K, Mager D, Richard C. How food processing im-
pacts hyperkalemia and hyperphosphatemia management
in chronic kidney disease. Can J Diet Pract Res 2020;81:132–6.
https://doi.org/10.3148/cjdpr-2020-003
75. Benini O, D’Alessandro C, Gianfaldoni D et al. Extra-
phosphate load from food additives in commonly eaten
foods: a real and insidious danger for renal patients. JRen
Nutr 2011;21:303–8. https://doi.org/10.1053/j.jrn.2010.06.021
76. Watanabe MT, Araujo RM, Vogt BP et al. Most consumed
processed foods by patients on hemodialysis: alert for
phosphate-containing additives and the phosphate-to-
protein ratio. Clin Nutr ESPEN 2016;14:37–41. https://doi.org/
10.1016/j.clnesp.2016.05.001
77. Picard K, Picard C, Mager DR et al. Potassium content of the
American food supply and implications for the manage-
ment of hyperkalemia in dialysis: an analysis of the Branded
Product Database. Semin Dial 2021. https://doi.org/10.1111/
sdi.13007
78. Kalantar-Zadeh K, Gutekunst L, Mehrotra R et al. Under-
standing sources of dietary phosphorus in the treatment of
patients with chronic kidney disease. Clin J Am Soc Nephrol
2010;5:519–30. https://doi.org/10.2215/CJN.06080809
79. de Boer IH, Khunti K, Sadusky T et al. Diabetes management
in chronic kidney disease: a consensus report by the Amer-
ican Diabetes Association (ADA) and Kidney Disease: Im-
proving Global Outcomes (KDIGO). Kidney Int 2022;102:974–
89. https://doi.org/10.1016/j.kint.2022.08.012
80. Rossing P, Caramori ML, Chan JCN et al. Executive summary
of the KDIGO 2022 clinical practice guideline for diabetes
management in chronic kidney disease: an update based
Downloaded from https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfad103/7152602 by guest on 07 June 2023

14 C. M. Avesani et al.
on rapidly emerging new evidence. Kidney Int 2022;102:990–
9. https://doi.org/10.1016/j.kint.2022.06.013
81. Avesani CM, Cardozo LF, Yee-Moon Wang A et al. Planetary
health, nutrition and chronic kidney disease: connecting the
dots for a sustainable future. JRenNutr2022. https://doi.org/
10.1053/j.jrn.2022.09.003
82. Willett W, Rockström J, Loken B et al. Food in the Anthro-
pocene: the EAT-Lancet Commission on healthy diets from
sustainable food systems. Lancet 2019;393:447–92. https://
doi.org/10.1016/S0140-6736(18)31788-4
83. EAT-Lancet Commission. Healthy diets from sustain-
able food systems. Food Planet Health. Summary report.
2020. https://eatforum.org/content/uploads/2019/01/
EAT-Lancet_Commission_Summary_Report.pdf
84. Leite FHM, Khandpur N, Andrade GC et al. Ultra-processed
foods should be central to global food systems dialogue
and action on biodiversity. BMJ Glob Health 2022;7:e008269.
https://doi.org/10.1136/bmjgh-2021-008269
85. da Silva JT, Garzillo JMF, Rauber F et al. Greenhouse gas emis-
sions, water footprint, and ecological footprint of food pur-
chases according to their degree of processing in Brazilian
metropolitan areas: a time-series study from 1987 to 2018.
Lancet Planet Health 2021;5:e775–85. https://doi.org/10.1016/
S2542-5196(21)00254-0
86. Lawrence M. Ultra-processed foods: a t-for-purpose con-
cept for nutrition policy activities to tackle unhealthy and
unsustainable diets. Br J Nutr 2022. https://doi.org/10.1017/
S000711452200280X
87. Monteiro CA, Astrup A. Does the concept of “ultra-processed
foods” help inform dietary guidelines, beyond conventional
classication systems? YES. Am J Clin Nutr 2022;116:1476–81.
https://doi.org/10.1093/ajcn/nqac122
88. Ministry of Health of Brazil. Dietary guidelines for
the Brazilian population. Brasilia: Ministry of Health,
2014.
89. Lichtenstein AH, Appel LJ, Vadiveloo M et al. 2021 di-
etary guidance to improve cardiovascular health: a sci-
entic statement from the American Heart Associa-
tion. Circulation 2021;144:e472–87. https://doi.org/10.1161/
CIR.0000000000001031
Downloaded from https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfad103/7152602 by guest on 07 June 2023

NephroCan is a Canadian, fully integrated product and service
provider for patients affected by chronic kidney failure and needing
hemodialysis (HD) therapy. Our company offers a broad range of HD
products including machinery: hemodialysis machine, central and
portable reverse osmosis (RO) systems, patient chairs, and disposables:
dialyzers, bloodlines, stula needles, and bicarbonate cartridges and
bags.
N
ephroCan’s dialyzers (NephroFilters) are made with high-quality
materials and pass rigorous testing to ensure safety, effectiveness,
and efcacy. We offer a variety of NephroFilters to assist nephrologists
and other healthcare providers in administering personalized care for
their patients. NephroFilters are low ux or high-ux permeability and
adaptable to different hemodialysis machines, designed for ease of
use by healthcare professionals.
O
ur HD machine (NephroHDM) features technology that enables
precise and customized treatment for each patient. Our goal is to
improve clinical outcomes and patient safety. The NephroHDM offers
various therapeutic options that allow healthcare providers to tailor
hemodialysis sessions based on each patient’s specic needs. The
machine is practical, with an intuitive interface for a fast, easy set up,
and safe monitoring of HD treatments.
NephroCan’s CE-certied products are trusted by healthcare
professionals around the world. Our commitment to quality and safety
is reected in our operations and processes, which ensure our products
provide patients with the best hemodialysis treatment throughout
their ESRD journey.
Our distribution partners and end users agree on several
reasons why NephroCan presents a unique offering: 
1. Extensive product portfolio
NephroCan offers a wide range of products and services that cover
the “A to Z” of the hemodialysis spectrum. This broad portfolio
provides integrated solutions and comprehensive treatments for
dialysis patients with various medical needs.
2. Commitment to innovation
NephroCan is committed to innovation and invests heavily in
research and development to create new products that can
improve patient outcomes. Our focus is to develop products and
technologies that will better serve the healthcare industry in the
coming years. 
3. Global perspective
With an existing presence in the EU, Africa, Asia, and the Middle
East, NephroCan’s goal is to expand our reach and serve patients
in diverse geographical areas. This global vision allows us to share
best practices and leverage expertise across regions to improve
patient care.
4. Patient and family-centred care approach
NephroCan places a strong emphasis on putting patients and
their families rst. We tailor our products and services to meet
the uniqueness of the communities we serve. This philosophy
is reected in our commitment to quality and safety, ensuring
NephroCan is a trusted provider of hemodialysis products.
You can learn more about how our products are driving positive
change in the industry and improving patient outcomes
worldwide by visiting our website: www.NephroCan.com.
We invite you to see our product portfolio
in person at the upcoming ERA 2023 congress:
Booth number
C.100
MiCo - Milano
Convention Center
June
15th - 17th