Original Research

Dietary Patterns, Apolipoprotein L1 Risk Genotypes, and

CKD Outcomes Among Black Adults in the Reasons for
Geographic and Racial Differences in Stroke (REGARDS)
Cohort Study
Titilayo O. Ilori, Marquita S. Brooks, Parin N. Desai, Katharine L. Cheung, Suzanne E. Judd,
Deidra C. Crews, Mary Cushman, Cheryl A. Winkler, Michael G. Shlipak, Jeffrey B. Kopp,
Rakhi P. Naik, Michelle M. Estrella, Orlando M. Guti errez, and Holly Kramer

Visual Abstract included

Rationale & Objective: Dietary factors may impact
inflammation and interferon production, which
could influence phenotypic expression of Apolipo-
protein1 (APOL1) genotypes. We investigated
whether associations of dietary patterns with kid-
ney outcomes differed by APOL1 genotypes.
Study Design: Prospective cohort.
Settings & Participants: 5,640 Black participants
in the Reasons for Geographic and Racial Differ-
ences in Stroke (REGARDS).
Exposures: Five dietary patterns derived from food
frequency questionnaires: Convenience foods,
Southern, Sweets and Fats, Plant-based, and
Alcohol/Salads.
Outcomes: Incident chronic kidney disease
(CKD), CKD progression, and kidney failure. Inci-
dent CKD was defined as a change in estimated
glomerular filtration rate (eGFR) to <60 mL/min/
1.73 m2 accompanied by a ≥25% decline from
baseline eGFR or development of kidney failure
among those with baseline eGFR ≥60 mL/1.73 m2
body surface area. CKD progression was defined
as a composite of 40% reduction in eGFR from
baseline or development of kidney failure in the
subset of participants who had serum creatinine
levels at baseline and completed a second in-home
visit/follow-up visit.
Analytical Approach: We examined associations
of dietary pattern quartiles with incident CKD
(n=4,188), CKD progression (n=5,640), and
kidney failure (n=5,640). We tested for statistical
interaction between dietary patterns and APOL1 Complete author and article
genotypes for CKD outcomes and explored strati- information provided before
references.
fied analyses by APOL1 genotypes.
Correspondence to T.O. Ilori
Results: Among 5,640 Black REGARDS partici- (Tilori1@bu.edu)
pants, mean age was 64 years (standard
Kidney Med. 5(5):100621.
deviation = 9), 35% were male, and 682 (12.1%) Published online March 6,
had high-risk APOL1 genotypes. Highest versus 2023.
lowest quartiles (Q4 vs Q1) of Southern dietary
doi: 10.1016/
pattern were associated with higher adjusted
j.xkme.2023.100621
odds of CKD progression (OR, 1.28; 95% CI,
1.01-1.63) but not incident CKD (OR, 0.92; 95% © 2023 The Authors.
Published by Elsevier Inc.
CI, 0.74-1.14) or kidney failure (HR, 1.48; 95% on behalf of the National
CI, 0.90-2.44). No other dietary patterns showed Kidney Foundation, Inc. This
significant associations with CKD. There were no is an open access article
statistically significant interactions between under the CC BY-NC-ND
license (http://
APOL1 genotypes and dietary patterns. Stratified
creativecommons.org/
analysis showed no consistent associations
licenses/by-nc-nd/4.0/).
across genotypes, although Q3 and Q4 versus
Q1 of Plant-based and Southern patterns were
associated with lower odds of CKD progression
among APOL1 high- but not low-risk genotypes.
Limitations: Included overlapping dietary patterns
based on a single time point and multiple testing.
Conclusions: In Black REGARDS participants,
Southern dietary pattern was associated with
increased risk of CKD progression. Analyses
stratified by APOL1 genotypes suggest associ-
ations may differ by genetic background, but
these findings require confirmation in other
cohorts.

rs60910145 (I384M) (G1) and rs71785313—a 6 base

A n individual’s preferences and access to healthy and
unhealthy foods translates to decades of dietary be-
haviors that can influence the development of chronic
diseases. Examining dietary patterns as an exposure for
disease risk such as chronic kidney disease (CKD) may be
more informative than focusing solely on 1 particular
nutrient or food group.1 Previous studies that examined
associations of dietary patterns with CKD outcomes did not
show consistent associations of dietary patterns with CKD
risk, but such differences could in part be due to hetero-
geneity in genetic risk for CKD. Approximately 13% of
African Americans carry ApolipoproteinL1 (APOL1) high-
risk genotypes, a 2-allele haplotype consisting of 2 non-
synonymous coding variants rs73885319 (S342G) or
pair deletion (G2).2 Only a minority of adults with the
APOL1 high-risk genotypes will develop CKD, which in-
dicates that a second factor is needed for phenotypic
expression of APOL1 high-risk variants.3 To date, factors
that increase interferon levels such as viral infections
strongly influence the phenotypic CKD risk in individuals
with APOL1 high-risk genotypes,4-7 but few studies have
examined the interaction of diet and APOL1 high-risk ge-
notypes on CKD outcomes. Diet influences innate immu-
nity and promotes pro- or anti-inflammatory effects by
immune cells and adipocytes, and this metabolic
inflammation/meta-inflammation may impact develop-
ment and progression of CKD.8,9 Diet also shapes the gut

Kidney Med Vol 5 | Iss 5 | May 2023 | 100621 1


PLAIN-LANGUAGE SUMMARY
Dietary patterns may influence phenotypic expression
of Apolipoprotein1 (APOL1) high-risk genotypes and
chronic kidney disease (CKD). Using data from the
Reasons for Geographic and Racial Differences in Stroke
(REGARDS) cohort, we examined whether associations
of 5 dietary patterns with CKD differed by APOL1 ge-
notypes. Mean age of Black REGARDS participants
(n=5,640) was 64 years and 35% were male; 12.1%
had high-risk APOL1 genotypes. Highest versus lowest
Southern dietary pattern quartile was significantly
associated with CKD progression (odds ratio, 1.28; 95%
confidence interval 1.01-1.63) but not incident CKD or
kidney failure. In exploratory stratified analyses, highest
versus lowest quartiles of Plant-based and Southern
patterns were associated with lower odds of CKD pro-
gression in APOL1 high-risk genotypes. Dietary patterns
are associated with CKD progression, but more studies
are needed.
microbiome, which may modulate the production of
interferon in response to viral infection.10,11 To our
knowledge, no previous study has examined whether the
association of dietary patterns with CKD outcomes differs
by the presence of APOL1 high-risk genotypes.
The aim of this study was to investigate whether the
association of dietary patterns with CKD outcomes differs by
the presence of APOL1 genotypes. We used data from the
Reasons for Geographic and Racial Differences in Stroke
(REGARDS) cohort to examine associations of 5 empirically
derived dietary patterns with CKD outcomes.12 We tested
for statistical interactions between dietary patterns and
presence of APOL1 high-risk genotypes. Subsequently, as an
exploratory analysis, we examined associations of dietary
patterns and CKD outcomes according to presence of APOL1
high-risk genotypes. We hypothesized that association of
dietary patterns with kidney outcomes differ by the pres-
ence of APOL1 genotypes.
METHODS
Setting and Participants
The REGARDS cohort is a population-based cohort
designed to examine geographic differences in stroke
incidence in Black and White adults in the United States
aged 45 years and older. Approximately half of the par-
ticipants (55.5%) were recruited from 8 Southeastern US
states with disproportionately higher stroke mortality rates
(Georgia, North Carolina, South Carolina, Tennessee,
Mississippi, Alabama, Louisiana, and Arkansas) compared
with other states, and 44.5% were recruited from all other
US states except for Hawaii and Alaska.13 Inclusion and
exclusion criteria for the REGARDS study have been
described, and race and ethnicity were self-reported.13 The
2 Kidney Med Vol 5 | Iss 5 | May 2023 | 100621
Ilori et al
study was designed to recruit an equal number of men and
women and to oversample Black adults. Potential partici-
pants were identified from commercially available lists;
residents were recruited through an initial mailing fol-
lowed by telephone contact. Overall, 30,239 individuals
were enrolled in REGARDS between January 2003 and
October 2007. Participants completed computer-assisted
telephone interviews followed by in-home study visits
conducted by trained health professionals that included
collection of fasting blood and urine samples. Research
personnel provided a 1998 Block Food Frequency Ques-
tionnaire (Block 98 FFQ, Nutrition Quest) for participants
to complete and mail back to the study center.14 Starting in
April 2013, participants were invited to undergo a second
in-person visit during which the baseline procedures were
repeated. Among the 16,150 participants who participated
in the second assessment, 15,938 completed the second
telephone-administered assessment and 14,449 had in-
person assessments, which were completed in December
2016. The REGARDS study protocol was approved by the
Institutional Review Boards at the participating centers,
and all participants provided informed consent.
Figure 1 shows the selection of the 5,640 Black
REGARDS participants included in the analyses of CKD
progression and incident kidney failure and the 4,188
Black participants included in the incident CKD analyses
(Fig 1).
Exposures
The primary exposures were the 5 dietary patterns previ-
ously derived from the REGARDS cohort: Convenience
foods, Southern, Sweets and Fats, Plant-based, and
Alcohol/Salads.12
Empirically Derived Dietary Patterns
The food frequency questionnaire includes frequency of
consumption and portion sizes of specific fruits and bev-
erages.15 Food frequency questionnaires were completed
by participants at home and mailed to the study center,
where they were checked for completeness. The scanned
files were sent to Nutrition Quest for analysis of nutrient
contents using algorithms.
Dietary patterns and factor loading values for 56 food
groups have previously been derived in the REGARDS
cohort using principal component analysis.12 Using the
scree plot and eigenvalues ≥1.5, a 5-factor solution was
retained based on loadings that contributed the most to
each pattern. In total, the 5 retained dietary patterns
explained w24% of the total variance in the study popu-
lation. All other factors explained less than 3% of the
variance. Congruence by ethnicity, region, and sex was
confirmed across the 5 patterns by deriving patterns
separately in each subpopulation.12
Five retained dietary patterns were defined according to
food group loadings;12 (1) The Convenience dietary
pattern was characterized by high factor loadings for
Ilori et al

A B
Total participants in REGARDS Total participants in REGARDS
N = 30,239 N = 30,239

Excluded individuals with data Excluded individuals with data

anomalies; n = 56 anomalies; n = 56

n = 30,183 n = 30,183
Excluded with baseline CKD;
n = 6,776
Excluded White participants; Excluded with baseline ESRD;
n = 17,669 n = 112
Excluded White participants;
Black participants in REGARDS Black participants in REGARDS n = 14,185
n = 12,514 n = 9,110
Excluded those with Excluded those with
Missing FFQ; n = 3006 Missing FFQ; n = 2148
Incomplete <15% of FFQ; n = 1652 Incomplete <15% of FFQ;
Implausible caloric intake; n = 581 n = 1063
Missing follow-up data; n = 434 Implausible caloric intake;
n = 416
n = 6,841 n = 5132 Missing follow-up data; n = 351

Missing data on covariates; n = 219 Missing data on covariates;

Missing APOL1 genotype data; n = 351
n = 982 Missing APOL1 genotype data;
n = 593
Final sample size Final sample size
n = 5,640 n = 4,188

Figure 1. Final Sample for (A) Exposures and incident ESKD/CKD Progression (B) Dietary Exposures and incident CKD (Bottom) in
the REGARDS study.

Chinese and Mexican food, pasta dishes, pizza, soup, and
other mixed dishes including frozen or take-out meals; (2)
the Plant-based pattern, by fruits, vegetables, and fish; (3)
the Sweets/Fats pattern, by desserts and carbohydrate-
heavy items; (4) the Southern dietary pattern, by organ
meats, fried foods, sugar-sweetened beverages, and
greens; and (5) the Alcohol/Salads pattern, by alcohol,
green-leafy vegetables, and salad dressing.
A dietary pattern score was calculated for each participant
by adding observed intakes of component food groups,
weighted by their respective factor loadings. The scores
were later divided into quartiles for the statistical analyses,
and dietary patterns were considered as continuous and
categorical variables, with quartile 1 (Q1) having the lowest
accordance to the dietary pattern and quartile 4 (Q4) having
the highest accordance to each dietary pattern. Unlike
cluster analysis, individuals may be in accordance with more
than 1 dietary pattern in factor analysis (Table S1).16
APOL1 Risk Genotypes
APOL1 risk variants G1 and G2 were genotyped in Black
participants using TaqMan SNP Genotyping Assays
(Applied Biosystems/Thermofisher Scientific). We defined
APOL1 risk genotype for each individual using a recessive
model, with the high-risk genotype individuals carrying 2
risk alleles (G1/G1, G2/G2 or G1/G2) and low-risk ge-
notype individuals carrying 1 or 0 risk allele (G1/G0, G2/
G0 or G0/G0).17
Outcomes
Serum creatinine was measured using isotope dilution
mass spectrometry-traceable methods. The 2021 race-free
CKD Epidemiology Collaboration creatinine-cystatin
equation was used to calculate estimated glomerular
filtration rate (eGFR).18
Among those who had a baseline eGFR ≥60 mL/min/
1.73 m2 at the first visit and completed the second in-
home visit (n=4,188), incident CKD was defined as a
change in eGFR to <60 mL/min/1.73 m2 accompanied by
a ≥25% decline from baseline eGFR or development of
kidney failure among those with baseline eGFR ≥60 mL/
1.73 m2 body surface area. CKD progression was defined
as a composite of 40% reduction in eGFR from baseline or
development of kidney failure in the subset of participants
who had serum creatinine level measured at baseline and
completed a second in-home visit/follow-up visit. Time to
kidney failure was assessed via linkage with the US Renal
Data System through June 30, 2018. Participants were
followed from the first visit to kidney failure, death, or
June 30, 2018, whichever came first.
Covariates
Covariates for adjustment in our analyses were a priori
determined based on known association with both the
exposure and the outcome via previous studies.19-29 Self-
reported highest levels of education achieved, family in-
come, age, and smoking status were obtained during the
baseline telephone interview. Systolic and diastolic blood
pressures were defined as an average of 2 seated blood
pressures taken after a 5-minute rest during the baseline
in-home visit. Hypertension was defined as blood pres-
sure ≥140/90 mm Hg or use of antihypertensive medica-
tion. Physical activity was assessed through a single
question “How many times per week do you engage in
intense physical activity, enough to work up sweat?”
Diabetes mellitus was defined by a fasting serum

Kidney Med Vol 5 | Iss 5 | May 2023 | 100621 3


glucose ≥126 mg/dL, nonfasting serum gluco-
se ≥200 mg/dL, or use of anti-diabetes medications.
Fasting blood samples were collected during baseline and
the follow-up in-home visits. Body mass index urine al-
bumin was measured by nephelometry using the BNII
ProcSpec nephelometer (now Siemens, Munich). We did
not include baseline eGFR and albuminuria in the main
analyses because we felt that this was part of the causal
pathway for kidney disease outcomes. Sensitivity analyses
were conducted that included adjusting for baseline eGFR
and albuminuria.
Analytical Approach
We examined baseline characteristics of participants
included in the kidney failure analyses (n=5,640) by
quartiles of dietary pattern scores for the 5 patterns derived
by factor analysis. Results are reported as mean and stan-
dard deviation, median and interquartile range, or counts
and proportions.
Multivariable logistic regression was used to determine
associations of dietary patterns with incident CKD and CKD
progression. We modeled the dietary patterns as quartiles.
Models were repeated using Poisson regression. We esti-
mated the associations of the same dietary patterns with
kidney failure using Cox proportional hazard regression.
We confirmed the assumptions of proportional hazards
using Schoenfield residuals and log-log plots. Models
adjusted for age, sex, region (random effect), caloric
intake, exercise, smoking status, education level, income,
hypertension, body mass index, history of diabetes, and
history of cardiovascular disease. Models were repeated
with death as a competing risk for kidney failure using
Fine and Gray model.30
We tested for interactions between dietary patterns and
APOL1 high-risk genotype status by introducing multipli-
cative interaction terms and adjusting for APOL1 high-risk
genotype status as a covariate. Subsequently, we stratified
the association of dietary patterns with kidney outcomes
by the presence of APOL1 high-risk genotype status. We
also tested for dietary patterns as a mediator of the asso-
ciation of APOL1 genotypes with CKD outcomes. A 2-tailed
P value < 0.05 was considered statistically significant for all
analyses. To account for multiple testing, we considered
the P for interaction significant when P < 0.01. Analyses
were conducted using SAS software version 9.4 (SAS
Institute Inc).
RESULTS
Descriptive Characteristics
Baseline characteristics by quartiles of dietary patterns for
these 5,640 participants are shown in Table 1. Among the
5,640 Black REGARDS participants included in the analyses
of CKD progression and kidney failure, mean age was 64
years (standard deviation = 9), 35% were male, and 682
(12.1%) had high-risk APOL1 genotypes (Table S2). Per-
centage of participants with high-risk APOL1 genotypes did
4 Kidney Med Vol 5 | Iss 5 | May 2023 | 100621
Ilori et al
not differ significantly by quartiles of any dietary pattern
(Table 1). Prevalence of diabetes increased across Conve-
nience and Southern dietary patterns. Table S2 shows
differences in characteristics by presence of high-risk
APOL1 genotypes. During a median follow-up of 11.6
years (interquartile range, 6.3-13.6 years), 3.2% (n=180)
developed kidney failure (37 with high-risk and 143 with
low-risk APOL1 genotypes), and 7.5% (n=440) showed
CKD progression (67 with high-risk and 363 with low-risk
APOL1 genotypes). High-risk APOL1 variants were present
in 11.3% (n=474) of the 4,188 Black REGARDS partici-
pants with baseline eGFR ≥60 mL/min/1.73 m2 and who
participated in a follow-up home visit. Over a median
follow-up of 9.5 years (interquartile range, 8.8-9.9 years),
incident CKD occurred in 7.4% (n=313) of this group
(n=32 with high-risk and 281 with low-risk APOL1
genotypes).
Characteristics of individuals who were and were not
included in the cohort examined for CKD progression and
kidney failure outcomes are shown in Table S1. Partici-
pants included in the analyses were more likely to be fe-
male, have diabetes and a higher body mass index, and
income <$20,000 (all P < 0.001) (Table S1).
Empirically Derived Dietary Pattern Scores and
CKD outcomes
Table 2 shows the associations of dietary pattern quartiles
with CKD outcomes. The highest quartile of a Southern
dietary pattern versus the lowest quartile was significantly
associated with CKD progression (odds ratio, 1.28; 95%
confidence interval [CI], 1.01-1.63) but not with incident
CKD (odds ratio, 0.92; 95% CI 0.74-1.14). The adjusted
risk of incident kidney failure was increased in the highest
versus lowest quartile of a Southern dietary pattern (hazard
ratio, 1.48; 95% CI 0.90-2.44), but the confidence interval
was wide and included 1.0 (Table 2). The upper quartiles
of all other dietary patterns compared with lowest quartile
were not significantly associated with any CKD outcome.
In models that used Poisson regression and adjusted for
baseline eGFR and albuminuria, the highest quartile of the
Southern dietary pattern versus lowest quartile was
significantly associated with increased rate of incident CKD
(relative rate, 1.41; 95% CI, 1.12-1.79) but not CKD
progression (relative rate, 1.11; 95% CI, 0.95-.29)
(Table S4). No dietary pattern was significantly associated
with kidney failure, and findings were similar when ana-
lyses accounted for death as a competing risk (Table 2).
Interaction Analyses
After adjustment for all covariates, no significant statistical
interaction was noted between the dietary patterns
(examined as quartiles or when modeled continuously),
APOL1 risk genotypes, and kidney outcomes (Fig 2A-C). As
an exploratory analysis, we stratified the selected cohorts
by presence of APOL1 risk genotypes and repeated analyses.
Figure 2A-C shows the associations of dietary patterns with
CKD outcomes in participants with high- and low-risk
Ilori et al

Table 1. Baseline Sociodemographic and Clinical Characteristics Across Quartiles of Dietary Patterns Among Black Individuals in
the REGARDS Cohort
Q1 Q2 Q3 Q4 P for trend
Convenience Dietary Pattern – Q1 desirable
Total N 1,410 1,410 1,410 1,410
Age (y) 66 (9) 64 (9) 62 (9) 62 (9) <0.001
Male 438 (31.1%) 455 (32.3%) 508 (36.0%) 566 (40.1%) <0.001
Income <$20,000 419 (29.7%) 354 (25.11%) 313 (22.2%) 354 (25.1%) <0.001
Smoking 0.005
Current 221 (15.7%) 246 (17.5%) 235 (16.7%) 299 (21.2%)
Past 542 (38.4%) 533 (37.8%) 552 (39.2%) 490 (34.8%)
Never 647 (45.9%) 631 (44.8%) 623 (44.2%) 621 (44.0%)
BMI (kg/m2) 30.4 (6.6) 30.9 (6.7) 30.6 (6.5) 31.5 (7.1) <0.001
Physical activity 0.37
None 512 (36.3%) 512 (36.3%) 500 (35.5%) 522 (37.0%)
1 to 3 times per wk 508 (36.0%) 551 (39.1%) 552 (39.2%) 514 (36.5%)
4 or more times per wk 390 (27.7%) 347 (24.6%) 358 (25.4%) 374 (26.5%)
Diabetes 392 (27.8%) 428 (30.4%) 356 (25.3%) 368 (26.1%) 0.01
eGFR (mL/min/1.73 m2) 80.5 (21.7) 83.0 (22.2) 85.9 (21.0) 87.2 (22.1) <0.001
ACR (mg/g) 8.0 [4.6-17.8] 7.4 [4.5-16.2] 7.1 [4.3-17.2] 7.3 [4.4-18.1] 0.08
APOL1 status 0.37
High risk 163 (11.6%) 159 (11.3%) 187 (13.3%) 173 (12.3%)
Low risk 1,247 (88.4%) 1,251 (88.7%) 1,223 (86.7%) 1,237 (87.7%)
Plant-Based Dietary Pattern – Q4 desirable
Total N 1,410 1,410 1,410 1,410
Age (y) 61 (9) 64 (9) 65 (9) 64 (9) <0.001
Male 588 (41.7%) 516 (36.6%) 449 (31.8%) 414 (29.4%) <0.001
Income <$20,000 378 (26.8%) 364 (25.8%) 358 (25.4%) 340 (24.1%) 0.43
Smoking <0.001
Current 403 (28.6%) 249 (17.7%) 196 (13.9%) 153 (10.9%)
Past 493 (35.0%) 552 (39.2%) 553 (39.22%) 519 (36.8%)
Never 514 (36.5%) 609 (43.2%) 661 (46.9%) 738 (52.3%)
BMI (kg/m2) 30.7 (6.9) 30.8 (7.0) 30.9 (6.6%) 31.0 (6.5) 0.25
Physical activity <0.001
None 612 (43.4%) 540 (38.3%) 492 (34.9%) 402 (28.5%)
1 to 3 times per wk 475 (33.7%) 524 (37.2%) 538 (38.2%) 588 (41.7%)
4 or more times per wk 323 (22.9%) 346 (24.5%) 380 (27.0%) 420 (29.8%)
Diabetes 330 (23.4%) 412 (29.2%) 393 (27.9%) 409 (29.0%) 0.001
eGFR (mL/min/1.73 m2) 85.6 (23.0) 82.6 (22.3) 83.2 (21.7) 85.1 (20.4%) 0.72
ACR (mg/g) 7.2 [4.4-17.6] 7.5 [4.4-18.5] 7.4 [4.5-17.1] 7.6 [4.6-16.7] 0.40
APOL1 status 0.54
High risk 165 (11.7%) 182 (12.9%) 159 (11.3%) 176 (12.5%)
Low risk 1,245 (88.3%) 1,228 (87.1%) 1,251 (88.7%) 1,234 (87.5%)
Sweets and Fats Dietary Pattern – Q1 desirable
Total N 1410 1,410 1,410 1,410
Age (y) 63 (8) 64 (9) 64 (9) 63 (9) 0.89
Male 450 (31.9%) 460 (32.6%) 509 (36.1%) 548 (38.9%) <0.001
Income <$20,000 329 (23.3%) 358 (25.4%) 359 (25.5%) 394 (27.9%) 0.05
Smoking <0.001
Current 220 (15.6%) 224 (15.9%) 263 (18.7%) 294 (20.9%)
Past 501 (35.5%) 525 (37.2%) 538 (38.2%) 553 (39.2%)
Never 689 (48.9%) 661 (46.9%) 609 (43.2%) 563 (39.9%)
BMI (kg/m2) 30.9 (6.7) 31.0 (6.6) 30.9 (6.9) 30.7 (6.8) 0.38
Physical activity <0.001
None 462 (32.8%) 501 (35.5%) 498 (35.3%) 585 (41.5%)
1 to 3 times per wk 554 (39.3%) 560 (39.7%) 523 (37.1%) 488 (34.6%)
4 or more times per wk 394 (27.9%) 349 (24.8%) 389 (27.6%) 337 (23.9%)
(Continued)

Kidney Med Vol 5 | Iss 5 | May 2023 | 100621 5

 Ilori et al

Table 1 (Cont'd). Baseline Sociodemographic and Clinical Characteristics Across Quartiles of Dietary Patterns Among Black In-
dividuals in the REGARDS Cohort
Q1 Q2 Q3 Q4 P for trend
Diabetes 425 (30.1%) 398 (28.2%) 387 (27.5%) 334 (26.7%) 0.001
eGFR (mL/min/1.73 m2) 85.1 (22.3) 85.3 (22.1) 83.0 (21.8) 85.2 (21.5) 0.98
ACR (mg/g) 7.5 [4.5-17.4] 7.6 [4.5-18.8] 7.1 [4.4-16.5] 7.5 [4.5-16.7] 0.47
APOL1 status 0.68
High risk 163 (11.6%) 167 (11.8%) 183 (13.0%) 169 (12.0%)
Low risk 1,247 (88.4%) 1,243 (88.2%) 1,227 (87.0%) 1,241 (88.0%)
Southern Dietary Pattern – Q1 desirable
Total N 1,410 1,410 1,410 1,410
Age (y) 64 (9) 65 (9) 64 (9) 62 (9) <0.001
Male 294 (20.9%) 411 (29.2%) 577 (40.9%) 685 (48.6%) <0.001
Income <$20,000 256 (18.2%) 358 (25.4%) 365 (25.9%) 461 (32.7%) <0.001
Smoking <0.001
Current 151 (10.7%) 235 (16.7%) 277 (19.7%) 338 (24.0%)
Past 562 (39.9%) 525 (37.2%) 527 (37.4%) 503 (35.7%)
Never 697 (49.4%) 650 (46.1%) 606 (43.0%) 569 (40.4%)
BMI (kg/m2) 30.4 (6.4) 30.5 (6.5) 31.3 (6.9) 31.2 (7.1) <0.001
Physical activity 0.16
None 501 (35.5%) 480 (34.0%) 531 (37.7%) 534 (37.9%)
1 to 3 times per wk 552 (39.2%) 553 (39.2%) 523 (37.1%) 497 (35.3%)
4 or more times per wk 357 (25.3%) 377 (26.7%) 356 (25.3%) 379 (26.9%)
Diabetes 336 (23.8%) 379 (26.9%) 408 (28.9%) 421 (29.9%) 0.002
eGFR (mL/min/1.73 m2) 84.5 (21.2) 83.4 (21.3) 84.3 (22.2) 84.4 (22.8) 0.91
ACR (mg/g) 6.8 [4.4-13.7] 7.1 [4.4-16.2] 7.7 [4.5-19.1] 8.5 [4.7-23.5] <0.001
APOL1 status 0.25
High risk 150 (10.6%) 183 (13.0%) 177 (12.5%) 172 (12.2%)
Low risk 1,260 (89.4%) 1,227 (87.0%) 1,233 (87.5%) 1,238 (87.8%)
Alcohol and Salads Dietary Pattern
Total N 1,410 1,410 1,410 1,410
Age 65 (9) 64 (9) 63 (9) 62 (9) <0.001
Male 460 (32.6%) 417 (29.6%) 525 (37.2%) 565 (40.1%) <0.001
Income <$20,0000 483 (34.3%) 372 (26.4%) 326 (23.1%) 259 (18.4%) <0.001
Smoking <0.001
Current 198 (14.0%) 235 (16.7%) 262 (18.6%) 306 (21.7%)
Past 466 (33.1%) 517 (36.7%) 542 (38.4%) 592 (42.0%)
Never 746 (52.9%) 658 (46.7%) 606 (43.0%) 512 (36.3%)
BMI (kg/m2) 30.4 (6.6) 31.0 (6.9) 31.0 (6.7) 31.1 (6.7) 0.005
Physical activity 0.06
None 507 (36.0%) 537 (38.1%) 501 (35.5%) 501 (35.5%)
1 to 3 times per wk 506 (35.9%) 526 (37.3%) 569 (40.4%) 524 (37.2%)
4 or more times per wk 397 (28.2%) 347 (24.6%) 340 (24.1%) 385 (27.3%)
Diabetes 372 (26.4%) 396 (28.1%) 410 (29.1%) 366 (26.0%) 0.21
eGFR (mL/min/1.73 m2) 81.0 (22.3) 83.0 (22.4) 84.8 (22.1) 87.8 (20.2) <0.001
ACR (mg/g) 7.5 [4.6-18.0] 7.6 [4.6-17.3] 7.4 [4.5-18.5] 7.1 [4.3-15.4] 0.04
APOL1 status 0.06
High risk 187 (13.3%) 187 (13.3%) 149 (10.6%) 159 (11.3%)
Low risk 1223 (86.7%) 1223 (86.7%) 1261 (89.4%) 1251 (88.7%)
Note: Categorical variables are expressed as n (%), and continuous variables are expressed as mean (standard deviation) or median [interquartile range]. N=5,640
sample size includes individuals in the incident end-stage renal disease and chronic kidney disease progression analyses.
Abbreviations: ACR, albumin creatinine ratio; APOL1, Apolipoprotein L1; BMI, body mass index, eGFR, estimated glomerular filtration rate.

APOL1 genotypes. The associations of the Plant-based and
Southern dietary pattern quartiles with CKD progression
appeared to differ by the presence of APOL1 genotypes. For
both dietary patterns, higher quartiles (Q3, Q4) versus
lowest (Q1) were associated with significantly lower odds
of CKD progression among participants with high-risk
APOL1 genotypes. In contrast, with low-risk APOL1 geno-
types, the highest quartile (Q4) versus lowest (Q1) for
Plant-based dietary pattern showed no association with
CKD progression whereas the highest quartile (Q4) versus

6 Kidney Med Vol 5 | Iss 5 | May 2023 | 100621

Ilori et al

Table 2. Associations of Dietary Patterns With CKD Outcomes Among Black Individuals in the REGARDS Cohort (N=4,188 for
Incident CKD Outcomes and 5,640 for CKD Progression and Incident CKD)
Incident Kidney Failure
Incident CKD CKD Progression Incident Kidney Failure (With Death As a
aOR (95% CI)* aOR (95% CI)* aHR (95% CI)* Competing Risk)
Events 313 440 180 180
Convenience Dietary Pattern (Q1 desirable)
Q1 Ref Ref Ref Ref
Q2 1.41 (1.06-1.88) 1.08 (0.67-1.73) 0.92 (0.61-1.38) 0.96 (0.63-1.47)
Q3 1.63 (1.48-1.79) 1.01 (0.80-1.26) 0.79 (0.51-1.24) 0.79.(0.49-1.27)
Q4 1.01 (0.84-1.22) 0.92 (0.71-1.19) 1.01 (0.63-1.61) 1.03 (0.62-1.72)
Plant-Based Dietary Pattern (Q4 desirable)
Q1 Ref Ref Ref Ref
Q2 0.89 (0.72-1.10) 0.92 (0.86-0.97) 1.17 (0.77-1.79) 1.16 (0.75-1.79)
Q3 0.72 (0.52-0.99) 0.98 (0.91-1.04) 0.93 (0.59-1.47) 0.94 (0.59-1.50)
Q4 0.95 (0.79-1.13) 0.95 (0.81-1.11) 1.24 (0.77-2.02) 1.25 (0.76-2.06)
Sweets and Fat Dietary Pattern (Q1 desirable)
Q1 Ref Ref Ref Ref
Q2 1.36 (1.00-1.83) 1.12 (0.96-1.30) 0.97 (0.63-1.48) 0.87 (0.56-1.34)
Q3 1.15 (0.75-1.75) 1.26 (1.02-1.57) 1.14 (0.74-1.74) 1.10 (0.71-1.71)
Q4 1.07 (0.71-1.60) 1.19 (0.90-1.58) 1.00 (0.59-1.69) 1.03 (0.61-1.72)
Southern Dietary Pattern (Q1 desirable)
Q1 Ref Ref Ref Ref
Q2 1.43 (1.15-1.78) 1.16 (0.85-1.59) 0.94 (0.60-1.48) 0.89(0.56-1.41)
Q3 1.18 (1.12-1.24) 1.07 (0.75-1.54) 0.88 (0.55-1.40) 0.86 (0.53-1.39)
Q4 0.92 (0.74-1.14) 1.28 (1.01-1.63) 1.48 (0.90-2.44) 1.42 (0.84-2.41)
Alcohols and Salad Dietary Pattern
Q1 Ref Ref Ref Ref
Q2 0.82 (0.66-1.03) 0.91 (0.68-1.21) 0.73 (0.48-1.11) 0.77 (0.51-1.18)
Q3 0.78 (0.53-1.15) 0.87 (0.77-0.98) 0.72 (0.47-1.10) 0.68 (0.43-1.05)
Q4 0.84 (0.48-1.45) 0.88 (0.71-1.11) 0.77 (0.50-1.18) 0.72 (0.46-1.13)
Note: *Models were adjusted for age, sex, region, caloric intake, exercise, smoking status, cardiovascular disease, hypertension, education level, income, body mass
index, and diabetes.
Abbreviations: aHR, adjusted hazard ratio; aOR, adjusted odds ratio; CI, confidence interval; CKD, chronic kidney disease.

lowest (Q1) showed significantly higher odds of CKD
progression (odds ratio, 1.53; 95% CI, 1.18-1.98) (Fig
2B). All other associations of dietary pattern quartiles
with CKD outcomes appeared similar by the presence of
APOL1 high-risk genotypes. Additionally, in the mediation
analyses, dietary patterns showed no evidence of statistical
significance as a mediator of the association of APOL1 ge-
notypes with CKD outcomes (Table S5).
DISCUSSION
This study examined the association of 5 dietary patterns
with incident CKD, CKD progression, and kidney failure in
a large cohort of Black individuals. Our analyses also
explored potential differences in the associations of dietary
patterns with CKD outcomes by the presence of APOL1
high-risk genotypes. Overall, no dietary pattern was
significantly associated with kidney failure, but higher
Southern dietary pattern accordance was significantly
associated with higher odds of CKD progression. In the
exploratory analyses stratified by APOL1 genotypes, the
association of Southern dietary pattern accordance with
CKD outcomes appeared to differ by presence of APOL1
high-risk genotypes, but the statistical interaction term did
not meet statistical significance. Exploratory analyses also
showed differences in the association of Plant-based di-
etary pattern with CKD progression, but interaction terms
did not meet statistical significance.
The findings of different associations of dietary patterns
with CKD progression in this study should be interpreted
with caution given the lack of statistically significant in-
teractions, but the findings deserve further investigation.
Dietary factors may influence inflammation and interferon
production in setting of a viral illness, which could
potentially influence the phenotypic expression of APOL1
variants. For example, many fruits and vegetables have a
high content of polyphenol compounds that downregulate
the gene expression of pro-inflammatory factors via inac-
tivation of nuclear factor kappa light chain enhancer of
activated B cells.31 Polyphenols also impede eicosanoid
production and block enzymes that lead to production of
reactive oxygen species while upregulating production of
antioxidant enzymes.31 The gut microbiota, shaped by
decades of habitual dietary patterns, produces small chain

Kidney Med Vol 5 | Iss 5 | May 2023 | 100621 7

 Ilori et al

Figure 2. (A) Associations of Dietary Patterns across APOL1 Genotypes in REGARDS for Incident CKD. (B) Associations of Di-
etary Patterns across APOL1 Genotypes in REGARDS for CKD Progression. (C) Associations of Dietary Patterns across APOL1
Genotypes in REGARDS for Incident Kidney Failure

fatty acids via fermentation of nondigestible dietary fiber. Other mechanisms that may link dietary patterns with
These small chain fatty acids have been shown to increase CKD also include higher blood pressure, inflammation,
interferon production in response to a viral infection.31 endothelial dysfunction, and insulin resistance.9,32,33 The

8 Kidney Med Vol 5 | Iss 5 | May 2023 | 100621

Ilori et al
Figure 2. Continued.
Southern dietary pattern is characterized by consumption
of fried foods, processed meats, and sugar-sweetened
beverages and the intake of red meat and has been asso-
ciated with heightened CKD risk and progression.34-36 The
Southern dietary pattern often includes collard greens,
which are rich in vitamins K and A and antioxidants.
We did not find consistent associations with Plant-based
dietary patterns and CKD outcomes. Reasons for the
inconsistent findings with the Plant-based pattern are
Kidney Med Vol 5 | Iss 5 | May 2023 | 100621
unclear and may be because of the misclassification of
dietary patterns. The finding of lower odds of CKD pro-
gression with high accordance to Plant-based dietary pat-
terns in participants with high-risk APOL1 variants deserves
further study given the recent report that higher potassium
intake may reduce CKD risk in individuals with high-risk
APOL1 variants.37 Plant-based diet could also decrease
CKD risk via reduction of dietary acid load, inflammation,
oxidative stress, and reductions in intraglomerular
9

Figure 2. Continued.
pressure.38-41 In a study among Black participants in the
African American Study of Kidney Disease and Hyperten-
sion (AASK), the high-risk APOL1 genotype was associated
strongly with CKD progression among Blacks with low net
endogenous acid production.42 However, several previous
older studies have shown no modification of association of
APOL1 genotypes with CKD progression by baseline uri-
nary excretion of potassium or estimated net endogenous
acid production.38,42-44
10
Ilori et al
To our knowledge, this is the first report that explores
the potential effect modification of APOL1 high-risk ge-
notypes on the association of dietary patterns with CKD
outcomes. In exploratory analyses, we found inconsistent
differences in associations of dietary patterns with high-
and low-risk APOL1 genotypes, which may warrant further
investigations with larger sample sizes. To date, factors that
increase interferon levels, such as infection with HIV
(human immunodeficiency virus) and SARS-CoV2 (severe
Kidney Med Vol 5 | Iss 5 | May 2023 | 100621
Ilori et al
acute respiratory syndrome coronavirus 2), modify the
phenotypic expression of the APOL1 high-risk genotypes
because interferon upregulates APOL1 expression in
podocytes.5,7,45 Although diet can influence inflammatory
markers, a previous study by Chen et al46 found that in-
flammatory biomarkers did not modify the association of
APOL1 genotypes and CKD outcomes.
This study has several limitations. First, the REGARDS
cohort was not specifically designed to examine the asso-
ciations of diet with CKD outcomes, and baseline urine
albumin-to-creatinine ratios were low, reflecting a low risk
for CKD outcomes. Secondly, dietary patterns were esti-
mated from a single time point in this older cohort, which
limits interpretability and generalizability when using di-
etary patterns to determine gene-diet interactions.47
Existing methodologies to model gene-diet interactions
using dietary patterns may not be optimal as the effects of
dietary patterns may be incremental and time-varying.47
Although largely employed in epidemiological studies,
food frequency questionnaires have some limitations with
nutrient accuracy and content, and this may pose a chal-
lenge in more complex analyses like diet by gene in-
teractions.48,49 Because the included cohort differs from
the participants who were not included, results may not be
representative of the entire REGARDS cohort.
In summary, we found that higher accordance with
Southern dietary pattern was associated with increased risk
for CKD progression, but this association may differ by
APOL1 genotypes. More studies are needed to determine if
the associations of dietary patterns with CKD outcomes
differ by presence of APOL1 high-risk genotypes. Such
information could help identify dietary patterns that can
modulate CKD risk, especially in adults with high-risk
APOL1 genotypes. Future studies of dietary patterns for
CKD risk should also consider use of 24-hour recalls,
duplicate dietary approach, food consumption records,
and dietary history records or other informative assess-
ments of dietary intake.
SUPPLEMENTARY MATERIAL
Supplementary File (PDF)
Figure S1: Kaplan-Meier Curve for the association of APOL1 risk
genotypes with incident kidney failure.
Figure S2: Associations of dietary patterns across APOL1 geno-
types in REGARDS for CKD outcomes.
Table S1: Food Group Loadings of the Dietary Patterns Derived
From the REGARDS Cohort.
Table S2: Baseline Characteristics of REGARDS Participants
Included in the Kidney Failure Outcomes Analyses Stratified by
ApolipoproteinL1 (APOL1) Risk Genotypes.
Table S3: Baseline Characteristics of REGARDS Participants
Versus Excluded Participants.
Table S4: Association of Dietary Patterns with Incident Chronic
Kidney Disease and CKD Progression, Using Poisson Regression.
Table S5: Mediation Analysis Results for APOL1 High-Risk Variants
and CKD Outcomes (CKD Progression, Kidney Failure, Incident CKD).
Kidney Med Vol 5 | Iss 5 | May 2023 | 100621
ARTICLE INFORMATION
Authors’ Full Names and Academic Degrees: Titilayo O. Ilori, MD,
MS, Marquita S. Brooks, MSPH, Parin N. Desai, MD, Katharine L.
Cheung, MD, PhD, Suzanne E. Judd, PhD, Deidra C. Crews, MD,
ScM, Mary Cushman, MD, Cheryl A. Winkler, PhD, Michael G.
Shlipak, MD, MPH, Jeffrey B. Kopp, MD, Rakhi P. Naik, MD,
Michelle M. Estrella, MD, Orlando M. Guti
errez, MD, and Holly
Kramer, MD, MPH.
Authors’ Affiliations: Division of Nephrology, Department of
Medicine, Boston Medical Center, Boston University School of
Medicine, Boston, MA (TOI); Department of Biostatistics, School
of Public Health, University of Alabama, Birmingham, AB (MSB,
SEJ); Division of Nephrology and Hypertension, Loyola University
Chicago, Maywood, IL (PND); Division of Nephrology, Department
of Medicine, Larner College of Medicine at The University of
Vermont, Burlington, VT (KLC); Division of Nephrology, Department
of Medicine, John Hopkins School of Medicine, Baltimore, MD
(DCC); Division of Hematology, Department of Medicine, Larner
College of Medicine at The University of Vermont, Burlington, VT
(MC); Basic Research Laboratory, Center for Cancer Research,
National Cancer Institute, National Institutes of Health and Leidos
Biomedical Research, Frederick National Laboratory, Frederick,
MD (CAW); Department of Medicine, University of California, San
Francisco, San Francisco, CA (MGS); Kidney Disease Section,
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), NIH, Bethesda, MD (JBK); Division of Hematology,
Department of Medicine, John Hopkins School of Medicine,
Baltimore, MD (RPN); Division of Nephrology, Department of
Medicine, San Francisco VA Medical Center, San Francisco, CA
(MME); Division of Nephrology, Department of Medicine, University
of Alabama, Birmingham, AB (OMG); and Department of Public
Health Sciences Division of Nephrology and Hypertension, Loyola
University, Chicago, IL (HK).
Address for Correspondence: Titilayo O. Ilori, MD, Boston
University School of Medicine, 650 Albany St, Boston, MA 02118.
Email: Tilori1@bu.edu
Authors’ Contributions: Contributions: research idea and study
design: TOI, SEJ, OMG, HK; data acquisition: MSB, SEJ; data
analysis/interpretation: MSB, DCC, MME, MGS, PND, RPN, SEJ,
KLC, MC, JBK, CAW, TOI, OMG, HK; statistical analysis: MSB,
SEJ; supervision or mentorship: SEJ, OMG, HK. Each author
contributed important intellectual content during manuscript
drafting or revision and accepts accountability for the overall work
by ensuring that questions pertaining to the accuracy or integrity
of any portion of the work are appropriately investigated and
resolved.
Support: This research project is supported by cooperative
agreement U01 NS041588 co-funded by the National Institute of
Neurological Disorders and Stroke (NINDS) and the National
Institute on Aging (NIA), National Institutes of Health, Department
of Health and Human Services. The content is solely the
responsibility of the authors and does not necessarily represent
the official views of the NINDS or the NIA. Dr Ilori is funded by
the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) K23DK119542 and the Department of
Medicine, Boston Medical Center. Dr Kopp is supported by the
Intramural Research Program, NIDDK, NIH, Bethesda. Dr Crews
was supported, in part, by grant 1 K24 HL148181 from the
National Heart, Lung, and Blood Institute, National Institutes of
Health.
Financial Disclosure: Dr Kramer is a consultant for Bayer
Pharmaceuticals and AstraZeneca. The remaining authors declare
that they have no relevant financial interests.
Acknowledgements: The authors thank the other investigators, the
staff, and the participants of the REGARDS study for their valuable
11

contributions. A full list of participating REGARDS investigators and
institutions can be found at: https://www.uab.edu/soph/
regardsstudy/
We would like to thank Sushrut Waikar MD, MPH and Josee Jos
ee
Dupuis, PhD for their contributions and insight toward the
manuscript and reading early versions of the manuscript.
Peer Review: Received June 22, 2022 as a submission to the
expedited consideration track with 4 external peer reviews. Direct
editorial input from the Statistical Editor and the Editor-in-Chief.
Accepted in revised form January 16, 2023.
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 Ilori et al

Do dietary patterns influence the risk of kidney disease

associated with different APOL1 genotypes?

Methods Results Associations between dietary patterns and kidney disease

Incident CKD CKD progression* Incident KF**
Dietary N = 4188 N = 5640 N = 5640
Prospective cohort study
patterns Highest vs lowest consumption, 95% CI

N = 5,640 Black participants Southern 0.92 (0.74, 1.14) 1.28 (1.01, 1.63) 1.48 (0.90 - 2.44)
in the Reasons for Geographic
and Racial Differences in Convenience 1.01 (0.84, 1.22) 0.92 (0.71, 1.19) 1.01 (0.63 - 1.61)
Stroke (REGARDS)
Sweets and fats 1.07 (0.71, 1.60) 1.19 (0.90, 1.58) 1.00 (0.59 - 1.69)
Mean age 64 years
Plant-based 0.95 (0.79, 1.13) 0.95 (0.81-1.11) 1.24 (0.77 - 2.02)
35% male
Alcohol/salads 0.84 (0.48, 1.45) 0.88 (0.71, 1.11) 0.77 (0.50 - 1.18)

12% with high-risk No statistically significant interactions between

*40% reduction in eGFR
APOL1 genotype from baseline or KF
APOL1 genotypes and dietary patterns
**KF – kidney failure

Conclusion: In this cohort, a Southern dietary pattern was associated with Reference: Ilori TO, Brooks MS, Desai PN et al. Dietary Patterns, Apolipoprotein
a higher risk of CKD progression. Analyses stratified by APOL1 genotypes L1 risk genotypes, and CKD outcomes among black adults in the REGARDS
cohort study. Kidney Medicine, 2023.
suggests associations may differ by genetic background but these findings
require confirmation in other cohorts. Visual abstract by Corina Teodosiu, MD @CTeodosiu

14 Kidney Med Vol 5 | Iss 5 | May 2023 | 100621