210 Nephrology Self-Assessment Program - Vol 18, No 4, September 2019 - Chronic Kidney Disease and Progression
Diet and CKD
Holly J. Kramer, MD, MPH
Department of Public Health, Parkinson School of Health Sciences and Public Health and Department of Medicine, Division
of Nephrology and Hypertension, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois
Sankar D. Navaneethan, MD, MS, MPH
Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston,
Texas Section of Nephrology, and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
High sodium intake mitigates BP control, one of the most important
interventions for prevention of CKD progression. Aside from its
effects on BP, high sodium intake may also exacerbate CKD pro-
gression via hemodynamic (1–3) and nonhemodynamic pathways
such as magnification of oxidative stress due to superoxide anion
generation (4,5) and/or upregulation of transforming growth factor-
b (TGF-b) (6,7). Regardless of its effects, research on imple-
mentation of sodium restriction for patients with CKD remains
poorly explored.
A recent, randomized, crossover trial by Saran et al. (8) dem-
onstrated that a sodium-restricted diet of 2 grams per day signifi-
cantly lowers extracellular volume, which will in turn improve BP
control. The sodium-restricted diet was implemented via in-person
dietary counseling by a registered study dietitian and motivational
interviewing. The counseling occurred at three separate time points
spaced by approximately 2 weeks. Participants also received phone
calls to encourage compliance with diet. Extracellular volume
measured by bioelectrical impedance spectroscopy was reduced by 1.l
L (−1.48 to −0.56 l) with the sodium-restricted diet. The mean
reduction in urinary sodium excretion after 4 weeks was 57.3 mEq/
day with the sodium-restricted diet, and 79% of the 56 participants
showed reductions in urinary sodium excretion with the sodium-
restricted diet. While such findings lend further support for sodium-
restriction for CKD management, more trials are needed to de-
termine more efficient methods for improving dietary behaviors,
including reducing sodium intake.
Coffee
Patients frequently ask what they can do to prevent progression of
CKD. Motivated patients frequently ask about their fluid intake and
diet. For example, in patients with polycystic kidney disease, re-
duction of caffeine intake has been recommended because caffeine
induces cyclic adenosine monophosphate, which is involved with cyst
growth (9). Recently, Lew et al. (10) completed an analysis of data
from a cohort study of approximately 63,000 adults living in Sin-
gapore followed for over 16 years to examine the risk of CKD as-
sociated with coffee consumption. Their analyses showed that
drinking at least two cups of coffee per day was associated with a
significantly lower risk of ESRD (hazard ratio [HR], 0.82; 95% CI,
0.71 to 0.96) than drinking no coffee. However, this association was
restricted to men.
Copyright © 2019 by the American Society of Nephrology
The effects of coffee intake on ESRD risk did not appear to be
mediated by caffeine intake because total caffeine intake from
noncoffee sources was not associated with ESRD risk. These
findings are supported by a recent study in the Atherosclerosis Risk
in Communities (ARIC) completed by Hu et al. (11). In this
analysis of 14,209 adult participants with baseline age of 45 to 64
years for 24 years, drinking at least one cup of coffee per day was
associated with a lower risk of incident CKD, defined as either a
25% or more reduction in baseline eGFR, or hospitalization for
CKD or ESRD. These associated benefits increased with greater
coffee intake. Each additional cup of coffee consumed per day
compared with no coffee consumption was associated with a 3%
lower risk of incident CKD over the follow-up period. Higher
coffee consumption was also associated with lower ESRD risk,
defined as kidney transplantation or initiation of dialysis per the
United States Renal Data System registry, after adjustment for
covariates (HR, 0.83; 95% CI, 0.54 to 1.28). After adjustment for
all covariates, including baseline eGFR, diabetes, and systolic BP,
no significant trend in ESRD risk was noted across quintiles of
coffee consumption (P=0.5) (11). Thus, coffee consumption is
possibly associated with a reduced risk of CKD, but more studies
are essential.
The association between coffee consumption and CKD risk
may be mediated in theory by chlorogenic acid, a dietary poly-
phenol with antioxidant and anti-inflammatory properties (12,13).
Glutathione is an important antioxidant that offsets injury from
oxygen radicals, especially in the renal inner medulla. Proximal
tubules do not synthesize glutathione, and their dependency on
circulating glutathione renders the medulla susceptible to oxidative
stress/injury. Damage to proximal tubules via oxidative stress is
considered an important mediator of kidney disease attributable to
diabetes and/or hypertension (14). Because chlorogenic acids
substantially increase glutathione levels (15), coffee consumption
may mitigate ischemic injury via its effects on glutathione levels and
other effects on oxidative stress and inflammation. However,
chlorogenic acids are found in other beverages. Besides coffee,
studies to date have only identified coffee as the beverage with
chlorogenic acid that reduces CKD risk. Therefore, other factors
that associate with coffee consumption such as behavioral factors
may be operative in mitigating kidney disease risk.
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Nephrology Self-Assessment Program - Vol 18, No 4, September 2019 - Chronic Kidney Disease and Progression
Sugar-Sweetened Beverages
While sugar-sweetened beverage (SSB) consumption has been
linked with weight gain, diabetes, gout, and heart disease, studies
have not consistently reported an association between SSB intake
and incident CKD (16). Rebholz et al. (22) examined beverage
patterns and risk of incident CKD in 3003 participants of the
Jackson Heart Study, a cohort of African American residents of
Jackson, MI. A unique food frequency questionnaire was specifically
developed to determine the beverage intake patterns of Mississippi
Delta region residents. The questionnaire was validated in the
Jackson Heart Study, and a baseline examination was administered
to this cohort from 2000 to 2004. Continuous scores were assigned
for each beverage pattern, with higher scores indicating greater
adherence to a particular beverage pattern. The identified beverage
patterns included several patterns: alcohol beverage, fruit and
vegetable juice, sweetened fruit drinks, artificially sweetened bev-
erage, low-fat milk, and a soda-and-water pattern categorized
as SSB.
For these analyses, incident CKD was examined as an estimated
GFR <60 ml/min per 1.73 m2 accompanied by a ≥30% eGFR
decline at follow-up relative to baseline eGFR. After a median follow-
up of 8 years, 6% of participants with baseline eGFR ≥60 ml/min per
1.73 m2 developed CKD. After adjustment for demographic and
socioeconomic factors, total energy intake, diabetes, and hyperten-
sion, the highest tertile of adherence to an SSB pattern was associated
with a 61% higher odds of incident CKD (95% CI, 1.07 to 2.41)
compared with lowest adherence to an SSB pattern. The association
of incident CKD with high adherence to an SSB pattern was
somewhat attenuated and not significant (odds ratio, 1.37; 95% CI,
0.86 to 2.16) after adjustment for dietary patterns. There was no
evidence that the association of SSB intake with incident CKD was
modified by baseline eGFR or diabetes status. The investigators
examined how individual types of beverages were associated with
incident CKD. After adjustment for covariates, the investigators
discovered that greater intake of soda was associated with incident
CKD (OR, 1.09; 95% CI, 1.00 to 1.18).
Notably, the SSB beverage pattern included soda and water
intake, and it is unknown whether the water was sweetened. This is
important because sweetened and flavored water is now a popular
drink option. The odds of incident CKD associating with SSB
pattern are weak, but the associations of dietary factors with health
outcomes are frequently underestimated because of nondifferential
misclassification of diet, including beverage intake. Such mis-
classification tends to bias measured associations toward the null.
Mississippi has one of the highest rates of SSB intake in the United
States (17). The beverage patterns in this region may not necessarily
mirror patterns in other areas of the United States. Accordingly, the
findings from the Jackson Heart Study may not be replicated in other
cohorts. Greater SSB intake and dietary factors that accompanied
SSB consumption in the Jackson Heart Study cohort may constitute
one reason for the positive association between SSB pattern and
incident CKD.
Diet Soda
To avoid the calories of SSBs, individuals frequently substitute
beverages with artificial sweeteners such as diet soda. The potential
metabolic harms of diet soda remain controversial because reported
211
weight gain noted with diet soda in observational studies may be
confounded by dietary habits (18). However, recent studies have
shown that nonnutritive sweeteners can upregulate adipogenesis and
directly stimulate insulin by binding to sweet taste receptors on
pancreatic beta cells (19–21).
Consequently, nonnutritive sweeteners found in diet soda
could lead to weight gain that would in theory increase the risk of
CKD via risks inherent to diabetes and hypertension. In addition,
caramelized diet soda often contains high amounts of phosphate-
containing preservatives that add to the dietary acid load, which may
exacerbate CKD progression. Dietary soda consumption assessed via
food frequency questionnaires was measured in the Atherosclerosis
Risk in Communities Study, a cohort of 15,368 adults with a mean
age of 54 years. Rebholz et al. (22) discovered a graded increase in the
risk of ESRD associated with greater diet soda consumption.
Drinking 5–7 glasses per week was associated with a 1.33-fold in-
creased risk of ESRD (95% CI, 1.01 to 1.75) and drinking >7 glasses
per week was associated with a 1.83-fold higher risk (95% CI, 1.01
to 2.52) after adjustment for demographics, BP, and serum uric
acid levels.
The results did not change after adjustments for dietary factors
and consumption of SSBs. Note that the association between diet
soda and ESRD was restricted to individuals overweight or obese at
baseline. So, it is possible that dietary behaviors or other poorly
measured factors fuel the association between dietary soda con-
sumption and ESRD risk rather than a particular component of the
diet soda itself. The findings from this study are supported by a
previous analysis of the Nurses’ Health Study in which con-
sumption of two or more diet sodas daily was associated with a
twofold increased odds of eGFR decline ≥30% (OR, 2.02; 95% CI,
1.36 to 3.01) and a ≥3 ml/min per 1.73 m2 per year eGFR decline
(OR, 2.20; 95% CI, 1.36 to 3.55) (23). In summary, these studies
suggest that diet soda consumption may increase the risk of CKD.
However, the disentanglement of beverage choice from other be-
havioral characteristics remains challenging, and these observations
are potentially biased by unmeasured confounders.
Water
Many websites tout the health benefits of drinking at least eight glasses
of water per day, and kidney health is often cited as a strong reason for
increasing water intake. Individuals seeking advice for the prevention
of kidney disease frequently request recommendations regarding ad-
equate water intake. Research, however, has never substantiated the
claim that greater water intake will reduce CKD risk or CKD pro-
gression. Nonetheless, we acknowledge that at least 2 liters of fluid
intake daily represents an important intervention for prevention of
recurrent kidney stones (24).
Current evidence proposes that patients with stages 1–2 CKD
polycystic kidney disease benefit from higher fluid intake provided
that they are not severely restricting protein or sodium intake and do
not take medications that affect diluting segments of the kidney or
vasopressin levels (25). Aside from these specific clinical scenarios,
many nephrologists do not support the lay community adage that
drinking one-half gallon of water daily benefits multiple aspects of
health, including kidney health (26,27). A previous study by Clark
and colleagues (28) showed that a lower urine volume in a 24-hour
period was associated with a faster rate of eGFR decline in the
212 Nephrology Self-Assessment Program - Vol 18, No 4, September 2019 - Chronic Kidney Disease and Progression
Walkerton Health Study, a cohort of adults age 18 years and older
with a baseline eGFRs >60 ml/min (mean eGFR, 87 ml/min per 1.73
m2) designed to determine the health consequences of exposure to
water contaminated with Escherichia coli 0157 and Campylobacter
species (28). Compared with the group with 24-hour urine volumes
of 1–1.9 L/day, individuals in the highest urine volume group (≥3 L/
day) had a 54% lower risk of an eGFR decline ≥5% compared with
baseline after adjustment for age, sex, baseline eGFR, dipstick
proteinuria, medication use, diabetes, and self-reported CVD. No
other urine volume group was significantly associated with higher or
lower odds of rapid eGFR decline compared with the referent group
(1–1.9 L/day). Similar findings were noted for mild to moderate
eGFR decline. Information on other dietary factors such as sodium,
potassium, fiber, total fat, and calories or body size were not included
in the analysis. These findings led to the development of the Chronic
Kidney Disease Water Intake Trial (29).
The Chronic Kidney Disease Water Intake Trial randomized 729
adults with stage 3 CKD and increased urine albumin excretion to
either a hydration group or a usual water intake group. All patients had
a baseline 24-hour urine volume <3 liters per day. After 1 year of
follow-up, the hydration group’s mean change in 24-hour urine
volume was 0.6 l/day (95% CI, 0.5 to 0.7 l) and mean eGFR change
−2.2 ml/min per 1.73 m2. The corresponding eGFR change in the
control group was −1.9 ml/min per 1.73 m2, with a mean group
difference, adjusted for demographics, of −0.3 ml/min per 1.73 m2
(95% CI, −2.8 to 1.2; P=0.74). No significant differences were noted
in change in urine albumin excretion. This trial did not show that
increasing water intake reduced the rate of GFR decline; however, the
study time was relatively short. A longer follow-up time is necessary to
more completely confirm that greater water intake mitigates CKD
progression. More trials are clearly required to fully appreciate the
impact of increasing water intake on CKD outcomes. Briefly, there is
currently no evidence that increasing water intake inhibits CKD
progression. Conversely, patients with kidney stone disease or early
stages of polycystic kidney disease (stages 1–2) should be encouraged to
drink more than 2 liters of fluid daily.
Sugar-sweetened and artificially sweetened bever-
age intake is associated with higher risks of non–
dialysis-dependent CKD. Increasing water intake has
not been shown to reduce the risk of kidney function
decline in clinical trials.
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