Effect of Coffee Consumption On Renal Outcome: A Systematic Review and Meta-Analysis of Clinical Studies

REVIEW ARTICLE
Effect of Coffee Consumption on Renal

Outcome: A Systematic Review and
Meta-Analysis of Clinical Studies
Mehmet Kanbay, MD,* Dimitrie Siriopol, MD,† Sidar Copur, MD,‡ Laura Tapoi, MD,§
Laura Benchea, MD,§ Masanari Kuwabara, MD,{ Patrick Rossignol, MD,** Alberto Ortiz, MD,††
Adrian Covic, MD,‡ and Baris Afsar, MD‡‡
Objective: Drinking coffee is one of the most common daily habits, especially in the developed world. Along with caffeine, coffee has
various ingredients that have been suggested to have beneficial effects, including antioxidant, antiinflammatory, anticarcinogenic, an-
tithrombotic and antifibrotic effects. In this systematic review and meta-analysis, we investigated the relationship between coffee intake
and chronic kidney disease (CKD) related outcomes.
Design and Methods: Literature search was performed through PubMed/Medline, Web of Science, Embase (Elsevier), and the Co-
chrane Central Register of Controlled Trials (Wiley) from 1960 to February 2020. Incidence of CKD, the progression of CKD, and CKD-
associated mortality have been evaluated in relation to coffee consumption and the amount of consumption. The Newcastle-Ottawa
scale was used for quality assessment of included studies.
Results: 12 studies were included in the analysis (7 prospective, 5 cross-sectional) involving 505,841 subjects. 7 studies investigated
the relationship between coffee consumption and incident CKD and showed that coffee consumption was associated with a significant
decrease in the risk for incident CKD outcome (RR 0.86, 95% CI 0.76 to 0.97, P 5 .01) with a greater decrease in individuals taking $2
cups/day compared to those who drank #1 cup/day. There was a significantly lower risk of incident end stage kidney disease (ESKD) in
coffee users (HR 0.82, 95% CI 0.72 to 0.94, P 5 .005). Coffee consumption was also associated with a lower risk of albuminuria (OR 0.81,
95% CI 0.68 to 0.97, P 5 .02). Overall, the risk of death related to CKD was lower in coffee users (HR 0.72, 95% CI 0.54 to 0.96, P 5 .02).
Conclusion: Coffee intake was dose-dependently associated with lower incident CKD, ESKD, and albuminuria.
Ó 2020 by the National Kidney Foundation, Inc. All rights reserved.
This article has an online CPE activity available at www.kidney.org/professionals/CRN/ceuMain.cfm
Introduction Increased oxidative stress via the formation of reactive ox-

ygen species (ROS) and the destruction of antioxidant
C HRONIC KIDNEY DISEASE (CKD), affecting
14% of the adult population in the USA, is an
epidemic with an increasing incidence that leads to signif-
mechanisms have been alleged to contribute to the patho-
physiology of adverse outcomes in CKD patients. Addi-
icant morbidity and mortality(1, 2). CKD is considered as tionally, many risk factors for CKD development and
12th leading cause of death worldwide, with cardiovascular progression are known to enhance the production of
disease (CVD) being the predominant cause of mortality in ROS. These risk factors include diabetes mellitus, hyper-
these patients.1-4 Furthermore, patients with CKD are also tension, alcohol consumption, and smoking.6-9
at significant risk for developing bone diseases, cognitive Coffee is one of the most commonly consumed bever-
impairment, anemia, CVD, infections, bleeding or ages, with a consumption rate of approximately 500 billion
thrombotic disorders, and electrolyte imbalances.3,5 cups/year. It contains a complex mixture of alkaloids (e.g.,
* ‡‡
Division of Nephrology, Department of Medicine, Koc University School of Division of Nephrology, Department of Internal Medicine, Suleyman Demi-
Medicine, Istanbul, Turkey. rel University School of Medicine, Isparta Turkey.
†
Department of Nephrology, Grigore T. Popa’ University of Medicine, Iasi, Financial Disclosure: The authors declare that they have no conflict of interest.
Romania. Support: This study was not funded by any grant.
‡
Department of Medicine, Koc University School of Medicine, Istanbul, Ethical approval: This article does not contain any studies with human partic-
Turkey. ipants or animals performed by any of the authors.
§
Department of Cardiology, ‘Grigore T. Popa’ University of Medicine, Iasi, Address correspondence to Mehmet Kanbay, MD, Division of Nephrology,
Romania. Department of Medicine, Koc University School of Medicine, 34010, Istanbul,
{
Department of Cardiology, Toranomon Hospital, Tokyo, Japan. Turkey. E-mail: [email protected]
**
Universite de Lorraine, INSERM CIC-P 1433, CHRU de Nancy, IN- Ó 2020 by the National Kidney Foundation, Inc. All rights reserved.
SERM U1116, FCRIN INI-CRCT (Cardiovascular and Renal Clinical 1051-2276/$36.00
Trialists), Nancy, France. https://doi.org/10.1053/j.jrn.2020.08.004
††
Dialysis Unit, School of Medicine, IIS-Fundacion Jimenez Diaz, Univer-
sidad Autonoma de Madrid, Avd. Reyes Catolicos 2, 28040, Madrid, Spain.
Journal of Renal Nutrition, Vol 31, No 1 (January), 2021: pp 5-20 5
Descargado para Anonymous User (n/a) en National Autonomous University of Mexico de ClinicalKey.es por Elsevier en marzo 03, 2022. Para
uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2022. Elsevier Inc. Todos los derechos reservados.
6 KANBAY ET AL
caffeine and trigonelline), diterpenes, chlorogenic acid, and Exclusion criteria included studies with missing data or
melanoidins that may have antioxidant, antiinflammatory, inadequate description of outcomes, studies not classified
anticarcinogenic, antithrombotic, and antifibrotic ef- as original articles (e.g. reviews, meta-analyses, editorials,
fects.10,11 Potential beneficial effects of coffee consumption commentaries), study types not listed as inclusion criteria
have been suggested in the cardiovascular, liver, and neuro- (e.g. case reports, case series), and unpublished data.
logical diseases and mortality and have been postulated to Assessment measures of this meta-analysis included the
be mediated by the antioxidant properties of coffee.12,13 incidence of CKD, the progression of CKD, and total or
Nevertheless, coffee also contains hydroxyhydroquinone, CKD-associated mortality. These assessment measures en-
which may generate ROS and induce single-strand DNA compassed changes in estimated glomerular filtration rate
breaks.14 Although a meta-analysis showed no association (eGFR) or serum creatinine, CKD-related deaths, cardio-
between coffee intake and CKD development,15 it was fol- vascular events or mortality, and total deaths. Details of
lowed by several large-scale studies with contradictory re- study selection procedures are depicted in Supplementary
sults.16,17 Therefore, no consensus has been reached Figure 1.
regarding the effect of coffee consumption on CKD. In
Quality Assessment
this systematic review, our aim is to assess the effect of coffee
Quality assessment of the studies included in the meta-
consumption on CKD development, CKD progression,
analyses was conducted in accordance with the
and CKD-related mortality in adults in light of recent
Newcastle-Ottawa Scale, which uses the selection of study
large-scale studies.
groups as the main criteria, assessment of outcomes, and
Methods comparability of the groups.21 According to the
Newcastle-Ottawa Scale, a study may be given up to nine
We performed this meta-analysis in accordance with the
stars, representing the highest quality research. The quality
Preferred Reporting Items for Systematic Review and
assessment of each study resulted from a consensus decision
Meta-Analyses (PRISMA) guidelines18 and Quality of Re-
by the authors.
porting of Meta-Analyses (QUOROM) statement19 and
the Cochrane Collaboration and Meta-analysis Of Obser- Statistical Analysis
vational Studies in Epidemiology (MOOSE).20 Extracted hazard ratios (HR) or odds ratios (OR) from
the included study protocols were pooled separately using
Literature Search and Inclusion/Exclusion
the random-effects model. The equivalent z test was per-
Criteria
formed for each pooled HR or OR, and if P was smaller
A literature search was performed through four data-
than .05, it was considered statistically significant. We con-
bases, including PubMed/Medline, Web of Science, Em-
verted standard deviation and 95% confidence interval to
base (Elsevier), and the Cochrane Central Register of
standard error using a standard formula.22 When necessary,
Controlled Trials (Wiley) from 1960 to February 2020 by
the individual OR and HR were combined using Peto’s
using the following medical subject headings: ‘‘coffee,’’
method. For the continuous variable (eGFR), the mean
‘‘coffee consumption,’’ ‘‘caffeine,’’ ‘‘caffeine intake,’’
difference was used to assess the effects of coffee consump-
‘‘chronic kidney disease,’’ ‘‘renal disease,’’ ‘‘renal failure,’’
tion. When different studies used both HR and OR for the
‘‘mortality,’’ ‘‘kidney failure’’ and ‘‘kidney disease.’’ Authors
same outcome, we reported the results as risk ratios (RR).
(S.C, M.K, and B.A) independently evaluated the titles, and
We assessed for heterogeneity in the treatment estimates
the abstracts of each study and conflicts were resolved by
using the Cochran Q test and the I2 statistic (with substantial
reaching a consensus after discussion and detailed examina-
heterogeneity defined as values greater than 50%).23 If a
tion of the study. References listed on selected studies were
sufficient number of studies were identified, subgroup anal-
also assessed manually in order not to miss any relevant
ysis was used to explore possible sources of heterogeneity.
study. After the preliminary selection, full texts of the
All statistical analyses were performed using Review Man-
selected studies were evaluated by the authors
ager (RevMan) Version 5.3 (The Cochrane Collaboration
independently.
2012).
Inclusion criteria for our systematic review and meta-
analyses are as follows:
Results
Study should investigate the association between cof- We included in our final analysis 12 studies: 7
fee consumption and incidence or progression of cohort16,17,24-28 and 5 cross-sectional studies.29-33 The
CKD or CKD-associated mortality. total number of evaluated participants was 506,062.
Cross-sectional studies and studies with retrospective Studies ranged from a minimum of 11431 to a maximum
or prospective design irrespective of randomization of 185,855 patients.26 General characteristics of the studies,
are included. including participant characteristics, inclusion and exclu-
Studies should be published in a peer-reviewed jour- sion criteria, intervention methods, outcome measures,
nal in English until February 2020. confounders adjusted in each study, and the Newcastle-
Table 1. Demographic and Clinical Characteristics of the Included Clinical Studies
Coffee consumption
definition and
Study Number of Characteristics of the Recruitment method Definition
Author, Year Location design participants participants method Exclusion criteria of evaluation of CKD
Nakajima Japan Cross- 342 246 M-96 F Patients of two Self-reported CVD, $1 cup/day GFR ,60
et al.,30 2010 sectional Recruitment: After a hospitals kidney diseases Questionnaire mL/min/
medical in Japan between or cancer 1.73 m2
check-up, no history age 30-80 who had
of kidney-cancer- undergone
CVD a medical check-up
BMI: 23.7 in coffee and who responded
consumers; to a questionnaire
23.5 in noncoffee about their lifestyle
consumers characteristics
BP: 119-74.5 in coffee
consumers;
123-76.1 in
COFFEE AND KIDNEY DISEASE

noncoffee
consumers
Smoking: 37.4% in
coffee consumers;
35% in noncoffee
consumers
Alcohol: 48.6% in
coffee consumers;
44.4% in noncoffee
consumers
Kotani Japan Cross- 114 age- 57 M-57 F Participants at age 40- CKD $1 cup/day eGFR , 60
et al.,31 2010 sectional gender Mean age: 59.5 (8.7) for 70 selected from CVD Questionnaire mL/min/
matched M and F database of Smoking 1.73 m2
participant BMI: 24.2 in coffee community-based
consumers; 24.3 in health
noncoffee check-up screening
consumers subjects
BP: 134.8-76.5 in
coffee-consumers;
136.7-75.3 in
noncoffee
consumers
(Continued )
7
Table 1. Demographic and Clinical Characteristics of the Included Clinical Studies (Continued )
8
Coffee consumption
definition and
Kim et Korea Cross- 2,673 0 M-2.673 F Participants at age Age over 85 $2 cup/day eGFR , 60
al.,32 2013 sectional Age: 56.5 for,1cup/ 35-64 performing Lack the data of Questionnaire mL/min/
day; 52.6 for 2 Fourth Korea DM or coffee use 1.73 m2
cump/day; 48.6 for National Health and
$2 cups/day Nutrition Examination
BMI: 23.7 for all groups surveys in 2008
BP: 118.5-75
for,1cup/day;
115.7-74.1 for
1 cup/day; 113.6-
74.2 for $2 cups/day
Significant variations at
alcohol intake,
use of DM-HT
medications; no
significant variation in
current
KANBAY ET AL
fasting lipid profile or
glucose level
Loftfield United Prospective 90,317 40.2% M in Participants at age Extreme calorie Different cups/day All and cause-
et al.,24 2015 States Cohort nonconsumers; 55-74 that are consumption analyzed specific
Study 44.5 M in included in PLCO (,1 or .99 independently mortalities
,1cup/day; 47.6% M Cancer Screening percentile) $4 cup/day were
in 2-3 cups/day; Trial. History of self- Questionnaire evaluated.
62.1 M in $6 cups/ reported CVD
day Malignancy history
Smoking: 4% in Missing data for
nonconsumers; 5.2% smoking or coffee
in ,1cup/day; 9.8% Noncompliance to
in 2-3 cups/day; follow-up
31.8% in $6 cups/
day
Alcohol: 17.1% in
nonconsumers;
34.6% in ,1cup/day;
50% in 2-3
cups/day; 43.2% in
$6 cups/day
Similar for DM, use of
aspirin and
ibuprofen, family
history
Herber- Netherlands Prospective 4,722 Smoking: 15.3% in Participants at age Missing data Food frequency GFR ,60 mL/
Gast cohort ,1cup/day; 26-65 that are Pregnancy questionnaire min/1.73 m2
et al.,25 2016 study 19.5% in 1-2 cups/ included in
day; 20.7% in 3-4 Doetinchem Cohort
cups/day; 27% in 5-6 Study group
cups/day;
40.8% in $6 cups/
day
Alcohol: 23.7% in
,1cup/day; 27.1%
in 1-2 cups/day;
32.2% in 3-4 cups/
day; 31% in 5-6 cups/
day; 29.6% in $6
cups/day
No significant
difference in gender,
BMI, BP, age,

baseline plasma
glucose levels
Girardat- Switzerland Cross- 151 91 M-60 F Participants at age Noncompliance to $2 cup/day eGFR , 60
Rotar sectional Mean age: 32.8 (69) 18-60 included in follow-up Questionnaire mL/min/
et al.,29 2018 BMI: 24.04 (64) eGFR: Swiss ADPKD Treatment with dis- 1.73 m2
90.78 (619) cohort between ease
overall; 95.8 (619) for 2008-2014 with modifying agents
noncoffee proven diagnosis of (Sirolimus, everoli-
consumers; 88.23 ADPKD and mus,
(619) for coffee eGFR .30 mL/min/ tolvaptan, somato-
consumers 1.73 m2 statin
Smoking: 36% overall; analogues etc.)
33% in possible
noncoffee
consumers; 37% in
coffee consumers
BP: 138.4-89 overall;
136.5-86.2 in
noncoffee
consumers; 139.4-
90.5 in
coffee consumers
Park United Prospective 185,855 Participants at age Implausible dietary Different cups/day All and cause-
et al.,26 2017 States cohort study 40-69 that are energy analyzed specific
included in MEC and macronutrient independently mortalities
cohort intake Questionnaire were
Missing information evaluated
Participants not in
top 5
ethnic groups
(Continued )
9
Table 1. Demographic and Clinical Characteristics of the Included Clinical Studies (Continued )
10
Coffee consumption
definition and
Jhee South Prospective 8,717 47.8% M-52.2% F Participants at age eGFR , 60 mL/min/ Food frequency eGFR , 60 mL/min/
et al.,16 2018 Korea cohort Mean age: 52.0 (8.8) 40-69 that are 1.73 m2 questionnaire 1.73 m2
Smoking: 29.1% in included in Known kidney Different cups/day
noncoffee KoGES cohort disease analyzed
consumers; 34.1% in Missing data independently
,1cup/week; Missing follow-up $1 cup/day
38.1% in 1-6 cups/ creatinine
week; 40.7% in
1cup/day; 56.4% in
$2 cups/day
Alcohol: 41.4% in
noncoffee
consumers;
49.5% in ,1cup/
week; 56.3% in
1-6 cups/week;
56.7% in
KANBAY ET AL
1cup/day; 62.6% in
$2 cups/day
No significant
difference in BMI, BP
or comorbidities
Lew Singapore- Prospective 63,257 Age: 56.6 in ,1cup/ Participants at age Known CKD Food frequency ESKD defined as at
et al.,28 2018 China cohort study day; 56.8 in 45-74 that are questionnaire least 1 of the
1cup/day; 56.2 in included in $1 cup/day following:
.1cup/day. Singapore-Chinese Serum creatinine
Smoking: 23% in Health Study cohort .10 mg/dL
,1cup/day; eGFR ,15
27% in 1cup/day; Undergoing hemodialy-
41% in .1cup/day. sis or peritoneal
Alcohol: 10% in ,1cup/ dialysis
day; 11% in Undergone kidney
1cup/day; 14% in transplantation
.1cup/day.
No significant
difference in
comorbidities,
BMI or red meat
intake.
Hu United Prospective 14,209 Age: 53.9 for noncoffee Participants at age Blacks from Wash- Food frequency Incident CKD is defined
et al.,13 States cohort study consumers; 45-64 that are ington questionnaire as at least 1 of the
2018 54.3 for ,1cup/day; included in the Country-Maryland, following:
54.6 for 1-2 cups/ Atherosclerosis Risk Minneapolis- eGFR ,60
day; 54.1 in Communities Minnesota .25% decline in eGFR
for 2-3 cups/day; Study Missing data CKD-related hospitali-

53.5 for $3cups/day. Neither being black zation or death or

Smoking: 44.7% for or white ESKD
noncoffee
consumers; 49.1%
for ,1cup/day;
57.9% for 1-2
cups/day; 64.7% for
2-3 cups/day; 76.6
for $3cups/day.
No significant
difference
in BMI, BP, or

comorbidities.
Kennedy United Prospective 133,814 N/A The United Kingdom Relatives up to 2nd Dietary questionnaire eGFR , 60 mL/min/
et al.,34 2020 Kingdom cohort study Biobank cohort degree (Nonspecified) 1.73 m2
including Noncoffee drinkers
subjects between Patients not from
age 40-73 white
recruited between British ancestry
2006 and 2013
Gaeini Iran Prospective 1,780 Participants included in CKD Food frequency eGFR ,60 mL/min/
et al.,17 2019 cohort study Tehran lipid and CVD questionnaire 1.73 m2
Glucose Study. HT
Missing data
Noncompliance to
follow-up
Specific diets
Under or over-
reports of
energy intakes
F-female, M-male, N/A-Not applicable, CVD-cardiovascular disease, HT-hypertension, CKD-chronic kidney disease, GFR-glomerular filtration rate, BP-blood pressure, BMI-body mass
index, ESKD-end stage renal disease, ADPKD-adult polycystic kidney disease, DM-diabetes mellitus, KoGES-The Korean Genome and Epidemiology Study, MEC-Multiethnic Cohort.
11
12
Table 2. Characteristics and Quality of the Studies
Quality assessment
Adjusted OR Outcome Confounder adjustment Evaluation of outcome (Newcastle-Ottawa scale)
Nakajima et al.,30 2010 0.74 (0.3-1.85) overall eGFR Age Coffee consumption is Selection: 3
0.74 (0.25-2.17) in males Alcohol associated with NIGFR Comparability: 2

1.41 (0.06-33.2) in females BMI independently of clinical Outcome: 3

BP confounders
Fasting glucose
LDL-HDL
Medication
Proteinuria
Sex
Smoking
Tea
Triacylglycerol
Kotani et al.,31 2010 Coffee drinkers had higher eGFR N/A Coffee consumption is Selection: 2
eGFR values linked to higher eGFR Comparability: 1
[73.9 6 16.5 (SD) mL/ values. Outcome: 2
min/1.73 m(2)] than
noncoffee drinkers
(68.6 6 11.7)
KANBAY ET AL
Kim et al.,32 2013 0.52 (0.35 to 0.91) Development of CKD Age Coffee consumption is Selection: 3
Alcohol consumption associated with Comparability: 2
BMI decreased risk of renal Outcome: 3
Calorie intake impairment especially in
DM middle and elderly-aged
Hypertension diabetic women.
Lipid lowering drugs
Loftfield et al.,24 2015 0.8 (0.74-0.87) overall Overall and Cause-Specific Age Coffee consumption is Selection: 3
mortality Mortality Alcohol consumption associated with lower Comparability: 2
0.62 (0.26-1.44) for kidney BMI risk for deaths from heart Outcome: 3
disease-related mortality Content of meals (Meat, disease, chronic
0.75 (0.63-0.9) for heart vegetables, fruits, satu- respiratory diseases,
diseases related rated fat, processed diabetes, pneumonia
mortality meat) and influenza and
Daily calorie intake intentional self-harm, but
Detailed smoking not cancer.
history
DM
Education
Employment status
Ibuprofen-Aspirin-Sup-
plemental vitamin use-
in last 12 months
Postmenopausal HRT
Race
Sex
Herber-Gast et al.,25 2016 0.76 (-0.28, 1.81) for , 1-2 eGFR Age Coffee consumption is Selection: 3
cup/day Alcohol consumption linked to slightly higher Comparability: 2
1.35 (0.25, 2.44) for 3-4 BMI eGFR, especially in Outcome: 2
cups/day Daily calorie intake patients aged $46 y.
1.36 (0.2-2.52) for 5-6 Education level
cups/day Energy-adjusted intake

1.61 (0.41-2.81) for . 6 of fibers-vitamin C-

cups/day protein-fat-saturated
fat
Energy-adjusted intake
of magnesium and
potassium
Gender
Hypercholesterolemia-
HT and DM
Smoking status
Tea intake
Time-dependent phys-

ical activity
Girardat-Rotar et al.,29 2.03 (-0.31-4.38) eGFR Age Coffee consumption is not Selection: 3
2018 BMI a risk factor for ADPKD Comparability: 2
BP progression. Outcome: 3
Gender
Smoking
Park et al.,26 2017 0.75 (0.52–1.08) for 1-3 Total and Cause-Specific Alcohol consumption Coffee consumption is Selection: 3
cups/month; 0.83 (0.61– Mortality BMI linked to lower risk for Comparability: 2
1.12) for 1-6 cups/week; DM deaths due to heart Outcome: 3
0.60 (0.46–0.78) for Education level disease, cancer,
1cup/day; 0.59 (0.45– Race respiratory disease,
0.79) for 2-3 cups/day; Smoking history stroke, diabetes and
0.42 (0.26–0.67) for $4 kidney disease.
cups/day. P for trend
,0.001
(Continued )
13
14
Table 2. Characteristics and Quality of the Studies (Continued )
Quality assessment
Adjusted OR Outcome Confounder adjustment Evaluation of outcome (Newcastle-Ottawa scale)
Jhee et al.,16 2018 0.73 (0.6-0.98) for CKD Incidence of CKD Age Coffee consumption is Selection: 3

incidence eGFR decline rate per year Alcohol consumption associated with Comparability: 2

-0.97 (-1.07 to -0.88) for BMI decreased risk of CKD Outcome: 2

noncoffee consumers; BP development.
-0.93 (-1.11 to -0.75) for DM and HbA1c
,1cup/week; 0.93 (-1.04 Daily intake of tea and
to -0.83) for 1-6 cups/ chocolate
week; -0.75 (-0.84 to Education level
-0.72) for $ 1 cup/day Gender
History of CVD or HT
Income
Log-transformed CRP-
Hemoglobin-Albumin-
eGFR-Total
cholesterol-Proteinuria
Smoking status
Lew et al.,28 2018 0.91 (0.79-1.05) for 1 cup/ Incidence of CKD Age Coffee consumption $2 Selection: 3
day Alcohol consumption cups/day reduces the Comparability: 2
0.82 (0.71-0.96) for .1
KANBAY ET AL
BMI risk of ESRD in the Outcome: 2
cup/day Consumption of black general population.
p-trend: 0.012 tea, green tea or soda
Dialect group
Education status
Gender
Physical activity
Red meat intake
Self-reported history of
DM, HT, stroke or CVD
Smoking status
Total protein intake
Hu et al.,13 2018 0.90 (0.82–0.99) ,1 cup/ Incidence of CKD DASH diet Coffee consumption is Selection: 3
day; 0.90 (0.82–0.99 for 1 DM linked to lower risk of Comparability: 2
to ,2 cups/day; 0.87 Gender incident CKD after Outcome: 2
(0.77–0.97) for 2 to ,3 Physical activity adjustment of
cups/day; , 0.84 (0.75– Smoking status covariates.
0.94) for $3 cups/day
Kennedy et al.,34 2020 0.84 (0.72-0.98) for 1 extra- Incidence of CKD eGFR BMI Participants who drank Selection: 3
cup/day for incident CKD DM higher amounts of coffee Comparability: 2
Hypertension had a lower risk of Outcome: 2
Smoking incident CKD and higher
eGFR after adjusting for
covariates.
COFFEE AND KIDNEY DISEASE 15
index, ESKD-end stage renal disease, ADPKD-adult polycystic kidney disease, DM-diabetes mellitus, HDL-high-density lipoprotein, LDL-low-density lipoprotein, DASH-diet approach to
F-female, M-male, N/A-Not applicable, CVD-cardiovascular disease, HT-hypertension, CKD-chronic kidney disease, GFR-glomerular filtration rate, BP-blood pressure, BMI-body mass
Ottawa assessment scale of studies are reviewed at Tables 1
and 2. CKD definition varied between studies, and eGFR
value was the most commonly preferred approach.
Although the quality assessment of studies via the
Newcastle-Ottawa scale revealed variations, included
Comparability: 2
studies have high scientific quality (Table 2).

Selection: 3
Outcome: 2
To calculate eGFR, 5 studies used the CKD-EPI creati-

nine equation,16,17,25,27,29 5 studies used the MDRD equa-
tion,28,30-33 and 2 studies did not specify.24,26
Five studies defined incident CKD as eGFR ,60 mL/
min/1.73 m2,16,17,30,32,34 while one study defined incident
Tea, coffee consumption or
linked to the risk of HT or

caffeine intake are not
CKD as at least one of the following eGFR ,60 mL/min/

1.73 m2 or .25% decline in eGFR at any subsequent study
visit relative to baseline.27
Two studies reported end stage kidney disease (ESKD)
incidence. One study defined incident ESKD as at least 1
CKD.
of the following: serum creatinine .10 mg/dL, eGFR

,15 mL/min/1.73 m2, undergoing hemodialysis or peri-
toneal dialysis, or undergone kidney transplantation.28
Dietary fiber and calorie
The other study identified ESKD by linkage to the US

Renal Data System (USRDS) registry as cases of kidney
Triglyceride/HDL-C
transplant or dialysis.27
One study defined albuminuria as urinary albumin-
creatinine ratio .17 mg/g (1.92 mg/mmol) in men and
Smoking
stop hypertension, CRP-c-reactive protein, HRT-hormone replacement therapy, HbA1c-hemoglobin A1c.

Gender
.25 mg/g (.2.83 mg/mmol) in women,34 and the second

intake
ratio
BMI
Age
one estimated albuminuria using dipstick urinalysis as fol-

lows: negative and borderline samples were categorized as
normal and the others as overt proteinuria.30
Regarding CKD mortality, 2 studies24,26 included in the
sub-analysis used the International Classification of Dis-
eases, Ninth Revision (ICD-9) codes 580-589 to classify
Incidence of CKD
the cause of death. One study26 used additional codes

from the 10th Revision: N00 to N07, N17 to N19, N25
to N27.
Coffee consumption was defined in different ways,
as follows: nondrinkers versus drinkers(17, 29-31); 1
cup/day versus $2 cups/day(28, 32); ,1 cup/day, 2-3
1.24) for 250-750 mg/day
day caffeine; 0.89 (0.63–
cups/day, $ 4cups/day24; ,1cup/day, 1-2 cups/day, 3-4

0.92 (0.68-1.25) .750 mg/
cups/day, 5-6 cups/day, .6 cups/day25; 1-3 cups/month,

1 cup coffee 5 65 mg
1-6 cups/week, 1cup/day, 2-3 cups/day, $4 cups/day26;

,1 cup/day, 1-2 cups/day, 2-3 cups/day, $3 cups/day27;
,1 cup/week, 1-6 cups/week, 1cup/day, $2cups/day.16
caffeine
One study included only coffee users.34

When estimating the risk for the different CKD
outcomes, 6 studies calculated HRs16,17,24,26-28 while 3
studies calculated the ORs.30,32,34
The median follow-up periods were reported by the
7 prospective cohort studies as follows: 6 years,17 9 years,24
Gaeini et al.,17 2019
11.3 years,16 15 years,25 16.2 years(26), 16.8 years,28

24 years.27
Outcome Measures Reporting

CKD Incidence
There were 6 studies, 3 prospective cohorts16,17,27 and 3
cross-sectional30,32,34 that analyzed the effect of coffee
16 KANBAY ET AL
Figure 1. Forest plot of the included studies for incident chronic kidney disease (CKD) according to coffee use. The comparator is
no coffee intake.
consumption on CKD incidence. As shown in Figure 1, ESKD Incidence

coffee consumption was associated with a significant ESKD incidence was evaluated in 2 prospective cohort
decrease in the risk for incident CKD defined using studies.27,28 Overall, there was a significant lower risk of
eGFR (RR 0.86, 95% CI 0.76 to 0.97, P 5.01, moderate incident ESKD in coffee users (HR 0.82, 95% CI 0.72 to
heterogeneity- I2 5 44%). 0.94, P 5 .005, insignificant heterogeneity- I2 5 0%)
We also analyzed the relationship between the risk of (Figure 2).
incident CKD and the frequency of coffee intake. Only 3 When analyzed according to the frequency of coffee
studies16,27,32 were used for the analysis, and coffee con- intake, the effect was significant and similar in both the cof-
sumption was summarized as #1 cup/day and $2 cups/ fee intake/#1 cup/day and the coffee intake/$2 cups/day
day. The effect on incident CKD was significant in both subgroups as compared to no coffee intake (Supplementary
subgroups (RR 0.87, 95% CI 0.77 to 0.98, P 5 .02 and Figure 3).
RR 0.82, 95% CI 0.74 to 0.92, P , .001 for the #1
Albuminuria
cup/day and the $2 cups/day subgroup, respectively,
There were 2 cross-sectional studies30,34 that reported
both compared to no intake), without a significant interac-
data on the association between coffee consumption and
tion between these subgroups (P 5.52 for the test for sub-
albuminuria. Coffee consumption was associated with a
group differences) (Supplementary Figure 2A).
lower risk of albuminuria (OR 0.81, 95% CI 0.68 to
There were 2 studies that assessed the effect of coffee
0.97, P 5 .02, insignificant heterogeneity- I2 5 0%)
consumption on CKD incidence according to gender:
(Figure 3).
one study32 included only women and the second one30
included more than twice men than women(246 men, 96 CKD Mortality
women). Although the effect was significant only in Two prospective cohort studies24,26 evaluated this
women coffee users (OR 0.60, 95% CI 0.38 to 0.96, outcome. We analyzed the association with CKD mortality
P 5 .03), the interaction test for subgroup differences was according to the frequency of coffee intake as follows: no
nonsignificant (Supplementary Figure 2B). coffee intake, #1 cup/day, 2-3 cups/day, $4 cups/day.
When separately analyzing the effect of coffee consump- Overall, the risk of death related to CKD was lower in cof-
tion on CKD incidence in prospective and cross-sectional fee users (HR 0.72, 95% CI 0.54 to 0.96, P 5.02, substan-
studies, statistical significance was reached only for the latter tial heterogeneity- I2 5 68%); we also observed a trend
(HR 0.90, 95% CI 0.75 to 1.09, P 5.29 and OR 0.70, 95% toward an increased beneficial effect in those with $4
CI 0.53 to 0.93, P 5 .02 respectively). cups/day (Figure 4).
Figure 2. Forest plot of the included studies for incident end stage renal disease (ESKD) according to coffee use. The comparator
is no coffee intake.
Figure 3. Forest plot of the included studies for albuminuria according to coffee use. The comparator is no coffee intake.
Coffee Consumption With Baseline eGFR 0.74 mL/min/1.73 m2, 95% CI -5.61 to 7.08 mL/min/
Four studies, 1 prospective cohort study25 and 3 cross- 1.73 m2, P 5 .82).
sectional studies,29-31 reported the mean and SD eGFR
values at baseline. One study25 reported eGFR values ac- Discussion
cording to the frequency of coffee intake. As shown in Coffee is one of the most consumed beverages world-
Supplementary Figure 4, there was no significant difference wide and is generally considered safe for CKD patients,
between coffee users and nonuser in regard to baseline although a number of caveats may limit its consumption
eGFR (mean difference0.74 mL/min/1.73 m2, 95% CI (potassium contents, phosphate from milk or additives,
-2.65 to 4.14 mL/min/1.73 m2, P 5.67, substantial hetero- amount of fluid, and acute pressor effect). Thus, online
geneity- I2 5 78%). After excluding the prospective cohort CKD patient sites discuss potential risks but no benefits
study from the analysis, the effect of coffee intake on base- and recommend not exceeding moderate consumption.35
line eGFR remained insignificant (mean difference Coffee contains over 1000 ingredients, some of which are
Figure 4. Forest plot of the included studies for chronic kidney disease (CKD) mortality according to the frequency of coffee
intake. The comparator is no coffee intake.
18 KANBAY ET AL
biologically active, including the alkaloid caffeine, diter- activated protein kinase (AMPK) and AMPK-dependent
penes, and chlorogenic acid, among others. The bioavail- decreased expression of epithelial sodium channels
ability of such ingredients depends upon individuals’ (ENaC) at collecting tubules.50 Kidney effects of desmo-
microbiome and genetics of transporters and en- pressin (DDAVP), prostaglandin E2 and isoproterenol are
zymes.33,36,37 As it is the case for items with widespread attenuated in subjects receiving caffeine.51 On the other
consumption, minimal effects may have significant hand, caffeine inhibition of adenosine receptors at juxtaglo-
population-wide health consequences. A large-scale merular cells increased renin levels, potentially activating
meta-analysis demonstrated coffee consumption is associ- the renin-angiotensinogen-aldosterone system. However,
ated with a lower risk for all-cause mortality, CVD inci- such an effect was not observed at physiological caffeine
dence and mortality, liver cirrhosis, certain malignancies concentrations.52,53 Urinary proteome analysis of 30
(i.e. hepatocellular carcinoma, prostate cancer, endometrial healthy subjects revealed decreased urinary kininogen-1 af-
cancer, skin cancer, leukemia), and type 2 diabetes melli- ter caffeine intake.54 This was postulated to potentially in-
tus.33,38,39 Linear dose-dependent beneficial effects have crease renal blood flow and GFR through vasodilatation
been described in certain malignancies such as prostate, resulting from the kidney accumulation of nonexcreted ki-
endometrium, liver cancer, and melanoma33,40-42 while nins.54 Also, caffeine intake was hypothesized to protect
nonlinear dose-dependent beneficial effects are observed from kidney stones, which through translocation of tubular
in all-cause mortality and CVD mortality.38 On the other cell annexin A1 from the apical surface toward the cyto-
hand, the association between coffee consumption and pa- plasm, thus decreasing the crystal-binding ability of tubular
rameters of renal function and CKD incidence has been surfaces.55 In contrast, chronic caffeine intake is thought to
investigated in relatively few studies. be a possible risk factor for cyst formation and enlargement
Previously, one previous meta-analysis, including four in patients with autosomal dominant polycystic kidney
observational studies (n 5 14,898) failed to observe any disease.51
beneficial effects of coffee consumption on CKD incidence Potentially detrimental effects of coffee consumption
in men and described the possibility of inverse association in should not be overlooked, such as arterial stiffness associated
women.15 Another recent meta-analysis study, including 4 with coffee consumption in the acute phase.56 In addition,
cohort studies with a total of 25,849 participants, investi- coffee is traditionally considered as proarrhythmogenic sub-
gated the effects of coffee consumption on incident CKD stance.57 However, this issue is now controversial since acute
incidence.43 Our study includes a higher number of studies ingestion of high doses of caffeine did not induce arrhythmias
with a higher number of participants in addition to the in patients with systolic heart failure who are at high risk for
assessment of effects of coffee consumption on various out- developing ventricular arrhythmias.58 At least in CKD pa-
comes. Additionally, we assess the relationship between the tients, these putative detrimental effects are not well studied.
amount of coffee consumption and outcomes. Our meta- However, our findings suggest that the beneficial effects of
analysis findings suggest that coffee consumption is associ- coffee may outweigh the potentially detrimental effects in
ated with beneficial outcomes in terms of risk for devel- the CKD population.
oping CKD or ESKD, CKD-related mortality, and We acknowledge that this meta-analysis has some limita-
albuminuria, with a trend toward increased beneficial ef- tions. Hence, these findings should be cautiously inter-
fects in those with $4cups/day, especially with regard to preted. Limitations of our meta-analysis include the lack
the mortality outcome. of randomized controlled trials and the inclusion of cross-
Molecular mechanisms of action of caffeine on cellular sectional studies. However, epidemiological studies are ex-
signaling primarily include competitive inhibition of G- pected to be key source information for this topic; a
protein coupled adenosine receptors, thus, decreasing beverage consumed in high amounts worldwide. Observa-
intracellular inositol triphosphate, diacylglycerol, and cal- tional studies cannot ascertain causality and may not have
cium signaling.44,45 Although earlier studies suggested fully accounted for the role of possible confounding factors,
that caffeine intake may impair renal blood flow, later including other dietary variables, comorbid medical condi-
studies demonstrated that caffeine increased GFR via inhi- tions such as diabetes mellitus and hypertension, family his-
bition of adenosine-induced vasoconstriction at afferent ar- tory, and individual genetic variations linked to kidney
terioles through type 1 adenosine receptors.46,47 Last, function, which should not be overlooked. However,
coffee-mediated inhibition of sodium reabsorption may most confounding factors are accounted for in the included
decrease kidney energy utilization, which may be beneficial studies. Another limitation of this meta-analysis is the vari-
in conditions of relative hypoxic such as acute ischemic kid- ability between the qualities of the included studies, which
ney injury and renal artery stenosis48 or any form of CKD were assessed via the Newcastle-Ottawa scale. The need for
with capillary rarefaction.49 future randomized controlled trials investigating the role of
Genetic-epigenetic changes and alterations of cell coffee intake on renal function preservation is clear.
signaling are detected in response to chronic coffee In summary, this meta-analysis showed that coffee con-
consumption such as phosphorylation of 50 AMP- sumption might improve renal outcomes. However, future
prospective, multi-center, well-designed studies are war- 13. Hu EA, Selvin E, Grams ME, Steffen LM, Coresh J, Rebholz CM.
ranted to formally evaluate the impact of coffee consump- Coffee consumption and incident kidney disease: results from the Atheroscle-
rosis Risk in Communities (ARIC) study. Am J Kidney Dis. 2018;72:214-222.
tion on renal outcomes. 14. Hiramoto K, Li X, Makimoto M, Kato T, Kikugawa K. Identification
of hydroxyhydroquinone in coffee as a generator of reactive oxygen species
that break DNA single strands. Mutat Res. 1998;419:43-51.
Practical Application 15. Wijarnpreecha K, Thongprayoon C, Thamcharoen N,
In our meta-analysis, we included 12 studies and demon- Panjawatanan P, Cheungpasitporn W. Association of coffee consumption
strated that coffee consumption was associated with a lower and chronic kidney disease: a meta-analysis. Int J Clin Pract. 2017;71.
risk of developing chronic kidney disease, chronic kidney https://doi.org/10.1111/ijcp.12919.
disease-related mortality, and albuminuria. The study 16. Jhee JH, Nam KH, An SY, et al. Effects of coffee intake on incident
chronic kidney disease: a community-based prospective cohort study. Am J
demonstrated a trend toward increased beneficial effects Med. 2018;131:1482-1490.e3.
in those with drinking $4 cups/day, especially in regard 17. Gaeini Z, Bahadoran Z, Mirmiran P, Azizi F. Tea, coffee, caffeine
to the mortality outcome in chronic kidney disease patients. intake and the risk of cardio-metabolic outcomes: findings from a population
with low coffee and high tea consumption. Nutr Metab. 2019;16:28.
18. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for
Acknowledgments reporting systematic reviews and meta-analyses of studies that evaluate health
MK gratefully acknowledges the use of the services and facilities of the care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62:e1-
Koc University Research Center for Translational Medicine (KUT- e34.
TAM), funded by the Presidency of Turkey, Presidency of Strategy and 19. Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF.
Budget. The content is solely the responsibility of the authors and does Improving the quality of reports of meta-analyses of randomised controlled
not necessarily represent the official views of the Presidency of Strategy trials: the QUOROM statement. Quality of Reporting of Meta-analyses.
and Budget. Lancet. 1999;354:1896-1900.
20. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational
studies in epidemiology: a proposal for reporting. Meta-analysis of Observa-
Supplementary Data tional Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008-
2012.
Supplementary data related to this article can be found at 21. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the
https://doi.org/10.1053/j.jrn.2020.08.004. assessment of the quality of nonrandomized studies in meta-analyses. Eur J Ep-
idemiol. 2010;25:603-605.
22. Higgins JPT, Thomas J, Chandler J, et al. eds.Cochrane Handbook for Sys-
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REVIEW ARTICLE

Effect of Coffee Consumption on Renal

This article has an online CPE activity available at www.kidney.org/professionals/CRN/ceuMain.cfm

Introduction Increased oxidative stress via the formation of reactive ox-

Journal of Renal Nutrition, Vol 31, No 1 (January), 2021: pp 5-20 5

COFFEE AND KIDNEY DISEASE

COFFEE AND KIDNEY DISEASE

for 2-3 cups/day; Study Missing data CKD-related hospitali-

53.5 for $3cups/day. Neither being black zation or death or

COFFEE AND KIDNEY DISEASE

0.74 (0.25-2.17) in males Alcohol associated with NIGFR Comparability: 2

1.41 (0.06-33.2) in females BMI independently of clinical Outcome: 3

cups/day Energy-adjusted intake

1.61 (0.41-2.81) for . 6 of fibers-vitamin C-

COFFEE AND KIDNEY DISEASE

-0.97 (-1.07 to -0.88) for BMI decreased risk of CKD Outcome: 2

studies have high scientific quality (Table 2).

To calculate eGFR, 5 studies used the CKD-EPI creati-

linked to the risk of HT or

CKD as at least one of the following eGFR ,60 mL/min/

of the following: serum creatinine .10 mg/dL, eGFR

The other study identified ESKD by linkage to the US

stop hypertension, CRP-c-reactive protein, HRT-hormone replacement therapy, HbA1c-hemoglobin A1c.

.25 mg/g (.2.83 mg/mmol) in women,34 and the second

one estimated albuminuria using dipstick urinalysis as fol-

the cause of death. One study26 used additional codes

cups/day, $ 4cups/day24; ,1cup/day, 1-2 cups/day, 3-4

cups/day, 5-6 cups/day, .6 cups/day25; 1-3 cups/month,

1-6 cups/week, 1cup/day, 2-3 cups/day, $4 cups/day26;

One study included only coffee users.34

11.3 years,16 15 years,25 16.2 years(26), 16.8 years,28

Outcome Measures Reporting

consumption on CKD incidence. As shown in Figure 1, ESKD Incidence

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