Nephrol Dial Transplant (2021) 36: 87–94

doi: 10.1093/ndt/gfaa314
Advance Access publication 19 December 2020

Chronic kidney disease is a key risk factor for severe

ORIGINAL ARTICLE
COVID-19: a call to action by the ERA-EDTA

ERA-EDTA Council and the ERACODA Working Group*

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Correspondence to: Alberto Ortiz, E-mail: [email protected]
*A list of members of the ERA-EDTA Council and the ERACODA Working Group can be found as
Acknowledgements section.

ABSTRACT RISK FACTORS FOR SEVERE COVID-19

Diabetes, hypertension and cardiovascular disease have been By October 2020, severe acute respiratory syndrome coronavi-
listed as risk factors for severe coronavirus disease 2019 rus 2 (SARS-CoV-2) causing the coronavirus disease 2019
(COVID-19) since the first report of the disease in January (COVID-19) pandemic had infected >35 million people with
2020. However, this report did not mention chronic kidney dis- >1 million deaths [1]. An enigmatic and perilous feature of
ease (CKD) nor did it provide information on the relevance of COVID-19 is the wide range of clinical manifestations from
estimated glomerular filtration rate (eGFR) or albuminuria. As asymptomatic to multiorgan failure and death. The high fre-
the disease spread across the globe, information on larger popu- quency of asymptomatic infection has undoubtedly contributed
lations with greater granularity on risk factors emerged. The re- to the rapid and worldwide spread of SARS-CoV-2 [2]. A key
cently published OpenSAFELY project analysed factors associ- unmet clinical need is the more precise and earlier identification
ated with COVID-19 death in 17 million patients. The picture of individuals at high risk of severe disease. These individuals
that arose differs significantly from initial reports. For example,
may benefit from shielding and be a priority group for vaccina-
hypertension is not an independent risk factor for COVID-19
tion and for early antiviral therapy before clinical deterioration.
death [adjusted hazard ratio (aHR) 0.89], but renal disease very
Although age is the leading risk factor for severe disease, even
much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53)
the elderly may be asymptomatic or have mild disease. Notably,
and CKD (aHR 2.52 for patients with eGFR <30 mL/min/1.73
Spain’s oldest woman, a survivor of the 1918 flu pandemic, sur-
m2) represent three of the four comorbidities associated with
the highest mortality risk from COVID-19. The risk associated vived mild COVID-19 that she probably acquired during her
with CKD Stages 4 and 5 is higher than the risk associated with 113th birthday celebrations [3]. The level of exposure to the vi-
diabetes mellitus (aHR range 1.31–1.95, depending upon gly- rus and viral load most likely play a role, as well as poorly char-
caemic control) or chronic heart disease (aHR 1.17). In another acterized genetic and immunological factors. Additionally,
recent publication, the Global Burden of Disease collaboration several comorbidities are associated with more severe COVID-
identified that worldwide, CKD is the most prevalent risk factor 19, emphasizing the need to study the disease-associated drivers
for severe COVID-19. Moreover, the distribution of risk factors of the higher risk and the potential impact on COVID-19 of
for COVID-19 mortality appears to be different in patients with medications commonly used for these diseases. Recently,
CKD when compared with the general population. The high chronic kidney disease (CKD) emerged as the most common
prevalence of CKD in combination with the elevated risk of risk factor for severe COVID-19 and alarmingly, after age, is
mortality from COVID-19 in CKD necessitates urgent action also the strongest risk factor for severe COVID-19 [4, 5].
for this group of patients. This article defines essential action
points (summarized in Box 1), among which is advocating the WHAT IS CKD?
inclusion of CKD patients in clinical trials testing the efficacy of
CKD is defined as a decrease in kidney function measured by
drugs and vaccines to prevent severe COVID-19.
glomerular filtration rate (GFR) or evidence of kidney damage
Keywords: chronic kidney disease, COVID-19, mortality, (even with normal GFR), such as increased albuminuria,
prevalence, renal replacement therapy, risk factor abnormal urine sediment or structural abnormalities persisting

C The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.

V
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/
by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-
use, please contact [email protected] 87
for >3 months, with implications for health [6]. The GFR and search for CKD and COVID-19 yielded >314 results and it has
albuminuria thresholds thought to have implications for health been found CKD is a key risk factor for severe COVID-19.
are <60 mL/min/1.73 m2 and >30 mg/g of urinary creatinine,
respectively. Despite the consensus CKD definition dating back CKD IS THE MOST PREVALENT RISK FACTOR
to 2012, there is still insufficient awareness of the concept and a FOR SEVERE COVID-19 WORLDWIDE
diagnosis of CKD is frequently not recorded in patient medical
The Global Burden of Disease (GBD) collaboration, which
records [7]. The prevalence of CKD in the adult population has
provides information on the health of populations worldwide
been estimated to be 10–15%, with 850 million people esti-
mated to have CKD globally. CKD is projected to become the annually, recently addressed the prevalence of risk factors for
fifth leading cause of death by 2040 worldwide and one of the severe COVID-19 worldwide [5, 18]. The GBD produces age-,
top two causes of death before the end of the century in some sex- and country-specific health estimates using highly stan-
European countries, particularly in those countries where life dardized, validated approaches applied to all available data
expectancy is longest [8–11]. Indeed, patients with CKD, espe- sources and adjusting for major sources of bias. Using 2017
cially those with kidney failure, are at increased risk of prema- prevalence data and UN population estimates for 2020, the
ture death from many causes, including, but not limited to, GBD estimated the number of individuals at increased risk of

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cardiovascular disease (CVD) and infections [12]. Therapeutic severe COVID-19 by age, sex and country for 188 countries.
nihilism (e.g. withholding drugs or interventions shown to be This study estimated the global population at high risk for se-
effective in the general population) was identified by multiple vere COVID-19 to be 1.7 billion people, comprising 22% of the
publications as a potential contributor to the high mortality global population, of whom 349 million would require hospital
[12]. admission if infected. CKD was the most prevalent risk factor
for severe COVID-19 worldwide [5]. It was the most common
risk factor and as frequent as CVD at any age (Figure 1).
DIABETES, HYPERTENSION AND CVD AS
Removal of CKD as a risk factor would decrease the percentage
RISK FACTORS FOR SEVERE COVID-19
of the global population at increased risk of severe COVID-19
The first report of COVID-19 in PubMed is a January 2020 from 22% to 17%. Thus CKD explains the increased risk of se-
Lancet manuscript describing that among patients admitted vere COVID-19 for about one in four high-risk individuals
with the disease, 20% had diabetes mellitus (DM), 15% hyper- worldwide (Supplementary data, Figure S1), equivalent to 5% of
tension and 15% CVD without any information on the the global population, or 86 530 000 persons.
prevalence of CKD, estimated GFR (eGFR) or albuminuria
[13]. By late March 2020, another report, also from China, listed
CKD IS THE DISEASE CONDITION
CKD status, finding it to be a comorbidity in only 1% of 274
CONVEYING THE HIGHEST RISK FOR
COVID-19 patients (median age 62 years), thus likely signifi-
SEVERE COVID-19
cantly underreporting the presence of CKD [14]. Chronic
hypertension and other cardiovascular comorbidities occurred Williamson et al. [4] recently published the largest analysis to
more frequently among deceased patients. A contemporary sys- date of risk factors for severe COVID-19 resulting in death.
tematic review and meta-analysis of 76 993 patients presented They analysed data from >17 million adults with almost 11 000
in 10 articles listed CKD among the seven most prevalent COVID-19-related deaths using OpenSAFELY, a health analyt-
coexisting diseases (alongside hypertension, CVD and DM) ics platform that covers 40% of all patients in England. In the
among hospitalized COVID-19 patients [15]. Another meta- abstract, the authors state that COVID-19-related death was as-
analysis of four studies including 1389 COVID-19 patients sociated with male sex [adjusted hazard ratio (aHR) 1.59 (95%
noted that although no study individually found CKD to be sig- CI 1.53–1.65)], older age, deprivation, DM, severe asthma,
nificantly associated with severe COVID-19, in the combined Black and South Asian ethnicity and ‘various other medical
analysis CKD was linked with severe COVID-19, without rele- conditions’. CKD is not mentioned in the abstract, yet from the
vant heterogeneity fodds ratio 3.03 [95% confidence interval full paper it is clear that advanced CKD (categories G4 and G5)
(CI) 1.09–8.47], I2 ¼ 0.0%, Cochran’s Q, P ¼ 0.84g [16]. was among the conditions conveying the highest risk of death
Furthermore, in March 2020, UK political and health authori- and notably higher than that conferred by all other factors
ties advised vulnerable persons, including those with CKD, to mentioned in the abstract. Indeed, in a fully adjusted model in-
‘shield’ (i.e. minimize their social contacts) [17]. This statement cluding adjustment for age, patients with kidney disease, for ex-
drew criticism for not considering the fact that CKD can vary ample dialysis patients (aHR 3.69), transplant recipients (aHR
from mild to severe and that this could have consequences [18]. 3.53) and CKD (aHR 2.52 for patients with eGFR <30 mL/min/
Thus early reports failed to adequately assess the prevalence of 1.73 m2, CKD G4–G5), represented three of the top four risk
CKD and to gauge its impact on COVID-19 disease severity categories. The risks in these subgroups were greater than the
and instead focused on CKD-associated conditions risk for COVID-19 death in diabetic patients (aHR range
(e.g. hypertension and DM). This is despite acknowledgement 1.31–1.95, depending upon glycaemic control) and in patients
of CKD as a known risk factor for severity of several other with chronic heart disease (aHR 1.17) (Figure 2). In sensitivity
bacterial and viral infections. As early as the end of March, analyses with different populations [early censoring, restricted
some authors were calling for CKD to be recognized as a high- to those with complete body mass index (BMI)/smoking data,
risk condition. Half a year later, in September 2020, a PubMed adjusted for recorded or imputed ethnicity], the risk conferred

88 ERA-EDTA Council and the ERACODA Working Group

 100 Chronic kidney disease 100 Cardiovascular disease

80 80

Prevalence (%)

Prevalence (%)
60 60

40 40

20 20

0 0
100 Chronic respiratory disease 100 Diabetes

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80 80
Prevalence (%)

Prevalence (%)
60 60

40 40

20 20

0 0
<5
5–9
10–14
15–19
20–24
25–29
30–34
35–39
40–44
45–49
50–54
55–59
60–64
65–69
70–74
75–79
80–84
85–89
90–94
≥ 95

<5
5–9
10–14
15–19
20–24
25–29
30–34
35–39
40–44
45–49
50–54
55–59
60–64
65–69
70–74
75–79
80–84
85–89
90–94
≥ 95
Age (years) Age (years)

FIGURE 1: Global prevalence of key underlying conditions associated with severe COVID-19 if infected. Prevalence by age. The four most
prevalent risk factors have been selected and ranked from left to right according to the highest global prevalence at any age range (bold black
line). Grey lines represent individual countries. Data from Clark et al. [5].

by CKD G4–G5 was consistently higher than the risk conveyed comorbidities that convey the highest risk of death in COVID-
by poorly controlled DM or severe asthma, which makes it all 19, it is replaced in the article ‘headline’ (i.e. the abstract) by
the more puzzling that CKD was not among the risk factors more ‘popular’ conditions that somewhat ironically are actually
detailed in the abstract. associated with a lower COVID-19 mortality risk than CKD.
Data for hypertension are interesting. Despite having been In a separate UK population-based cohort study undertaken
widely mentioned as a risk factor for severe COVID-19, in an in a general practice context, age and eGFR were the variables
analysis adjusted for age and sex it was only weakly associated that most strongly affected the aHRs for COVID-19-related
with the risk of death [HR 1.09 (95% CI 1.05–1.14)]. In a fully death in people with type 1 (T1DM; n ¼ 264 390) and type 2 di-
adjusted analysis, the risk associated with hypertension was in abetes (T2DM; n ¼ 2 874 020) (Figure 3) [21]. The increased
fact reversed [aHR 0.89 (95% CI 0.85–0.93)], thus suggesting risk was evident from eGFR 45–59 mL/min/1.73 m2, but not
that hypertension may be a surrogate for other conditions (e.g. with an eGFR above that value, in both T1DM and T2DM, i.e.
CKD) that convey the risk. A further explanation might be that it was evident for patients with CKD as defined by eGFR thresh-
the risk associated with hypertension is influenced by the use of olds. Unfortunately, similar to the OpenSAFELY study, the ef-
certain drugs [e.g. renin–angiotensin system (RAS) blockers]. fect of increased albuminuria was not analysed. Thus the
Although initially hypothesized that RAS blockade may in- increased risk of persons with CKD G3–G5 was confirmed, but
crease the risk of severe COVID-19 by increasing angiotensin- information on CKD G1–G2 was lacking, as in other epidemio-
converting enzyme 2 expression (and subsequent virus entry logical studies. Of the different variables analysed, an eGFR
into cells) or decrease the risk of severe COVID-19 by promot- <15 mL/min/1.73 m2 conferred the highest risk of death after
ing angiotensin(1-7) synthesis, neither of these hypotheses has age, both in T1DM [aHR compared with eGFR 90 mL/min/
been proven thus far in epidemiological studies, which instead 1.73 m2 8.35 (95% CI 5.50–12.70)] and in T2DM [aHR 4.91
tend to show a neutral effect [18, 19]. The potential impact of (95% CI 4.34–5.56)]. Other variables analysed included sex,
RAS blockade was not assessed in OpenSAFELY. Ultimately, socio-economic status or deprivation, ethnicity, haemoglobin
even when CKD is clearly demonstrated to be among A1c, BMI, blood pressure, antihypertensive drugs, smoking

Chronic kidney disease key risk factor for COVID-19 89

status and cardiovascular comorbidities. HRs for impaired kid- Results from the ERA-EDTA Registry further support the
ney function were consistent for males and females and were high mortality due to COVID-19 in dialysis patients and kidney
greater for people <70 years of age. transplant recipients across Europe [22]. The 28-day mortality
was 20.0% (95% CI 18.7–21.4%) in 3285 patients receiving dial-
ysis and 19.9% (17.5–22.5%) in 1013 recipients of a kidney
4.0
transplant. Mortality risk was 1.28 (95% CI 1.02–1.60) times
Adjusted hazard ratio for COVID-19 mortality

3.5 higher in transplant recipients compared with age- and sex-

matched dialysis patients. In both groups, mortality is in large
3.0 part related to age and in dialysis patients also to frailty status
[23]. In addition, frequent hospital attendance, as is needed for
2.5 in-centre dialysis, may increase the risk of infection for end-
stage kidney disease patients [24].
2.0
A missing piece of information is quantification of the risk con-
1.5 veyed by pathological albuminuria. This may be the sole criterion

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that defines CKD when eGFR is 60 mL/min/1.73 m2 or may fur-
1.0 ther increase risk in CKD patients with a lower eGFR. Interestingly,
COVID-19 itself may result in glomerular injury, evidenced by the
0.5 occurrence of proteinuria, which can be associated with acute kid-
ney injury [25]. In turn, acute kidney injury can lead to CKD, and
0
when superimposed on CKD, it increases the risk for mortality con-
s

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ic ag y

se

d)

se

n
n
si

og yr anc

io
er se m pla

lle
o

ea
ly

4–

ns

veyed by CKD even further [26, 27]. These data also indicate that
se

KD

tro
ia

is

te
G
an

di
D

td
C

on

er
ne d al

KD
al
r

SARS-CoV-2 has multiorgan tropism that includes glomerular and,

ar
di tolo an t

yp
nc
C

he

H
(u
al
rg

O gn ic

as was later shown, tubular cells [28, 29].

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hr
ia
a

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a
em

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th
H

END-STAGE KIDNEY DISEASE AND THE

FIGURE 2: Risk factors for COVID-19-related death. Graph shows
NEED FOR SPECIFIC STUDIES
the five medical conditions associated with the highest HRs of death Emerging data revealed risk factors for severe COVID-19
and, additionally, the risk associated with CKD G3 and the risk asso- among patients on kidney replacement therapy. The European
ciated with the risk factors recognized early in the pandemic as asso- Renal Association COVID-19 Database (ERACODA) cohort,
ciated with severe COVID-19 (diabetes, chronic heart disease and
established by the ERA-EDTA, showed that within dialysis and
hypertension, in black). In red, conditions of nephrological interest.
Light blue represents non-kidney risk factors present in <100 indi-
kidney transplant populations the risk conferred by classical
viduals. Data derived from Williamson et al. [4]. Patients with CKD risk factors for severe COVID-19 is completely different than in
G4–G5 have an eGFR <30 mL/min/1.73 m2 and patients with CKD the general population [23]. For instance, in dialysis patients
G3 have an eGFR of 30–60 mL/min/1.73 m2. with COVID-19 [n ¼ 768, of which 192 (25%) died], the rela-
tive contribution of age to mortality is considerably less than in

A B
Hazard ratio for COVID-19 mortality

10 12 ++++
T1DM T1DM < 70 yr T1DM ≥ 70 yr
T2DM T2DM < 70 yr T2DM ≥ 70 yr
* * 10
8

8
6 ++++
6 ++++
4 * *
4
* * * * ++++
2
2 ++

0 0
≥ 90 60–89 45–59 30–44 15–29 <15 ≥ 90 60–89 45–59 30–44 15–29 <15
eGFR (mL/min per 1.73 m2) eGFR (mL/min per 1.73 m2)

FIGURE 3: CKD as a risk factor for COVID-19-related death in T1DM and T2DM patients in general practice. (A) The aHRs for COVID-19-
related death according to type of diabetes and eGFR range. (B) The aHRs for COVID-19-related death according to type of diabetes, age and
eGFR range. An eGFR 90 mL/min/1.73 m2 was the reference for both graphs and was considered to be 1 in each of the categories (T1DM,
T2DM and age categories within) assessed. *P < 0.0001 versus eGFR 90 mL/min/1.73 m2; þ, non-overlapping 95% CI versus eGFR 90 mL/
min/1.73m2. Data derived from Holman et al. [20].

90 ERA-EDTA Council and the ERACODA Working Group

 A
Characteristics Adj. HR (95% CI)
Age (years)
• 50–59 (ref.) 1.00 (ref.)
• 60–69 2.40 (2.16, 2.66)
• 70–79 6.08 (5.52, 6.69)
• 80+ 20.61 (18.72, 22.70)
Sex
• Female (ref.) 1.00 (ref.)
• Male 1.59 (1.53, 1.65)
Body mass index (kg/m2)
• < 30 (ref.) 1.00 (ref.)
• 30–34.9 1.05 (1.00, 1.11)
• 35–39.9 1.40 (1.30, 1.52)
Diabetes
• No (ref.) 1.00 (ref.)
• Yes (HbA1c ≥ 58 mmol/mol) 1.95 (1.83, 2.07)

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Hypertension
• No (ref.) 1.00 (ref.)
• Yes 0.89 (0.85, 0.93)
Chronic heart disease
• No (ref.) 1.00 (ref.)
• Yes 1.17 (1.12, 1.22)
Respiratory disease ex. asthma
• No (ref.) 1.00 (ref.)
• Yes 1.63 (1.55, 1.71)
0.25 0.5 1 2 5 10
Adjusted hazard ratio and 95% CI
B
Characteristics Adj. HR (95% CI)
Age (years)
• 50–59 (ref.) 1.00 (ref.)
• 60–69 1.25 (0.67, 2.33)
• 70–79 2.95 (1.69, 5.16)
• 80+ 3.50 (1.97, 6.23)
Sex
• Female (ref.) 1.00 (ref.)
• Male 1.11 (0.78, 1.59)
Body mass index (kg/m2)
• < 30 (ref.) 1.00 (ref.)
• 30–34.9 1.26 (0.83, 1.92)
• 35–39.9 2.12 (1.23, 3.65)
Diabetes
• No (ref.) 1.00 (ref.)
• Yes 1.00 (0.72, 1.39)
Hypertension
• No (ref.) 1.00 (ref.)
• Yes 0.56 (0.38, 0.82)
Coronary artery disease
• No (ref.) 1.00 (ref.)
• Yes 1.03 (0.74, 1.43)
Chronic lung disease
• No (ref.) 1.00 (ref.)
• Yes 1.05 (0.68, 1.63)
0.25 0.5 1 2 5 10
Adjusted hazard ratio and 95% CI

FIGURE 4: Risk factors for COVID-19-related death. Left graph shows the situation in subjects of the general population (as derived from the
OpenSAFELY study; data from Williamson et al. [4]) and the right graph shows the situation in patients with end-stage kidney disease treated
by maintenance haemodialysis (as derived from the ERACODA cohort; data derived from Hilbrands et al. [23]).

subjects from the general population. In addition, in dialysis The mortality rates in dialysis and transplant cohorts
patients, male sex, hypertension, coronary artery disease and di- clearly demonstrate that these are high-risk populations
abetes do not confer an independent increased risk of mortality [22, 23]; given the discrepancies between risk factors in
(Figure 4). this population as compared with the general population

Chronic kidney disease key risk factor for COVID-19 91

 Box 1. Background why CKD is important for the COVID-19 pandemic, resultant clinical and research consequences, and action points
Background
A. CKD is among the most prevalent conditions that increase the risk of severe COVID-19.
B. CKD is the condition that is most strongly associated with the risk of severe COVID-19.
C. Particularly in advanced CKD, the normal risk factors for severe COVID-19 are less important.
D. Patients with advanced CKD may be at additional increased risk of SARS-CoV-2 infection because of frequent hospital attendance.
E. A CKD diagnosis may be missed by physicians, especially in environments in which eGFR is not calculated automatically from serum creatinine by clin-
ical laboratories and where albuminuria is not routinely measured.

Clinical and research consequences and related action points

1. The study of the immune and inflammatory response to SARS-CoV-2 in CKD patients may provide clues to the pathogenesis of COVID-19 and
successful treatments for CKD patients with COVID-19.
Action point: Research into the immune and inflammatory response to SARS-CoV-2 at different stages of CKD should be encouraged.
2. The impact of increased albuminuria on COVID-19 severity in patients with eGFR categories G1 and G2 and also G3–G5 should be studied
Action point: Epidemiological research should be stimulated to clearly define the role of CKD, including elevated albuminuria, as a risk factor for severe
COVID-19.

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Action point: Consideration should be given to making testing for proteinuria/albuminuria mandatory for all individuals who test positive for
COVID-19 and are admitted to hospital.
3. Patients with CKD have a high risk of COVID-19-related complications, including mortality. This notwithstanding, at least 70–75% (in ESKD) of
CKD patients survive.
Action point: A CKD diagnosis should not be used as the sole criterion to deny vital supportive care to CKD patients with severe COVID-19.
Action point: Once CKD is identified, consider prompt transfer to a higher level of care.
4. Risk factors for COVID-19 mortality cannot be extrapolated from the general population to the CKD population.
Action point: Epidemiological research should be encouraged to investigate which factors can be of help to triage which CKD patients will benefit most
from more invasive treatment, including vital support care.
5. Patients of all CKD categories should be represented in vaccine and drug trials, including patients on maintenance haemodialysis and those with a
kidney transplant.
Action point: Actively encourage the inclusion of CKD patients in vaccine and drug trials.

[23], findings in the general population cannot and should such patients different vaccination schedules may be nec-
not be extrapolated to end-stage kidney disease popula- essary (e.g. a higher dose or repeat vaccinations).
tions. There are other compelling reasons why the CKD
population merits specific study. During the last 2 decades
it has become clear that some drugs that are effective in CONCLUSIONS
patients with normal kidney function have little or no effi- Although not listed in initial reports as a risk factor for severe
cacy in patients with impaired kidney function, especially COVID-19, CKD has emerged not only as the most prevalent
in those on dialysis. This holds true for, among others, sta- comorbidity conveying an increased risk for severe COVID-19,
tins [30]. Medications prescribed to lower COVID-19 mor- but also as the comorbidity that conveys the highest risk for se-
bidity and mortality must therefore be tested in patients vere COVID-19. The increased risk is evident below the thresh-
with impaired kidney function to prove their efficacy in old of eGFR that defines CKD and the risk increases as the
this patient category. Unfortunately, randomized clinical eGFR decreases, with the highest risk in patients on kidney re-
trials often exclude patients with impaired kidney function placement therapy. Although CKD patients are known to be at
due to safety reasons [10]. It is our recommendation that increased risk of death due to infectious diseases, the factors
the kidney community should take great care to include contributing to their greater vulnerability for severe COVID-19
CKD patients in COVID-19 medication trials to avoid dis- should be explored, as these may provide valuable insights into
parities in the treatment of this patient group. A first step therapeutic approaches to the disease in this patient group. It is
in achieving this is propagating awareness of the impor- presently unknown if earlier categories of CKD (G1/G2, i.e.
tance of CKD as a key risk factor among the general com- patients with preserved kidney function but with increased al-
munity and policymakers so that the problem is buminuria) are also at an increased risk of severe COVID-19,
recognized. Furthermore, we know that because of the im- and this must be explored. Moreover, the recognition that CKD
munosuppressive nature of the uraemic milieu in dialysis significantly contributes to the severity of COVID-19 should
patients and because of the use of immunosuppressants in now result in focused efforts to improve outcomes for the 850
transplantation patients, these patients respond poorly to million global CKD patients [8]. Paramount to this is the enrol-
vaccination [31]. It is therefore imperative that CKD ment of patients representing all CKD stages, including dialysis
patients be included in trials testing the efficacy of vaccines and transplantation, in clinical trials of vaccines to prevent and
against SARS-CoV-2 infection. It is very plausible that in drugs to treat COVID-19.

92 ERA-EDTA Council and the ERACODA Working Group

 7a
Crucially, a CKD diagnosis should not be used as the sole Department of Nephrology and Renal Transplantation,
criterion to deny intensive care admission with severe COVID- Patras University Hospital, Patras, Greece.
8b
19. Both scientific societies and patient associations should be Department of Internal Medicine, Maastricht University
vigilant in this regard. Until better epidemiological data become Medical Center, Maastricht, the Netherlands.
9b
available and the biological basis of the increased risk of severe ERA-EDTA Registry, Dept. Medical Informatics,
COVID-19 in CKD patients is ascertained, therapeutic nihilism Amsterdam University Medical Center, Amsterdam Public
may continue to play a role and CKD patients may be denied vi- Health Research Institute, Amsterdam, the Netherlands.
10a
tal support based on their increased risk of COVID-19-related Division of Nephrology, Ambroise ParÕ University
death. This becomes an unacceptable self-fulfilling prophecy. Hospital, APHP, Boulogne-Billancourt/Paris, France.
11a
The threatening shortage of intensive care unit capacity in some Centre for Research in Epidemiology and Population
parts of the world may have contributed to the high mortality Health (CESP), INSERM UMRS 1018, UniversitÕ Paris-
of CKD patients in these areas. In those with kidney disease, Saclay, UniversitÕ Versailles Saint Quentin (UVSQ),
therapeutic nihilism has been repeatedly associated with ad- Villejuif, France.
12a
verse outcomes [11]. Facing an ongoing pandemic of unquanti- Department of Internal Medicine, Division of Nephrology,

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fiable duration, this is not an acceptable strategy, particularly Medical University of Graz, Graz, Austria.
13a
considering the high prevalence of CKD. We propose that those 1st Department of Internal Medicine, Third Faculty of
with CKD must be actively included in research to ensure equi- Medicine, Charles University, Faculty Hospital KrÃlovskÕ
table access to effective vaccines and treatments in the future. Vinohrady, Prague, Czech Republic.
14a
Department Nephrology, Vall d’Hebron Hospital
SUPPLEMENTARY DATA Universitari, Vall d’Hebron Barcelona Hospital Campus,
Nephrology Research Group, Vall d’Hebron Institut de
Supplementary data are available at ndt online. Recerca (VHIR), Barcelona, Spain.
15a
Glasgow Renal and Transplant Unit, Queen Elizabeth
ACKNOWLEDGEMENTS University Hospital, Glasgow, UK.
16a
We would like to thank individual nephrologists and national Inherited Kidney Diseases Nephrology Department,
registries of kidney replacement therapy for providing data Fundació Puigvert Instituto de Investigaciones Biomédicas
on COVID-19 mortality for analyses by the ERACODA col- Sant Pau, Universitat Autónoma de Barcelona, Barcelona,
laboration (Hilbrands et al. [23]) and the ERA-EDTA Spain REDINREN, Barcelona, Spain.
17a
Registry (Jager et al. [22]). Division of Nephrology, Department of Internal Medicine,
The list of collaborative authors on behalf of the aCouncil School of Medicine, Marmara University, Istanbul, Turkey.
18b
of the European Renal Association and the European Dialysis Department of Clinical Pharmacy and Pharmacology,
and Transplantation Association (ERA-EDTA) and the University Medical Centre Groningen, University Hospital
b
Working Group of the European Renal Association COVID- Groningen, Groningen, the Netherlands.
19a
19 Database (ERACODA): Alberto Ortiz1a, Mario Division of Nephrology, University of Würzburg,
Cozzolino2a, Raphaël Duivenvoorden3b, Danilo Fliser4a, Denis Würzburg, Germany.
Fouque5a, Casper F.M. Franssen6b, Dimitrios Goumenos7a,
Marc H. Hemmelder8b, Luuk B. Hilbrands3b, Kitty J. Jager9b,
Ziad A Massy10a,11a, Marlies Noordzij6b, Alexander FUNDING
R.Rosenkranz12a, Ivan Rychlık13a, Maria Jose Soler14a, Kate ERACODA received unrestricted grants from the ERA-
Stevens15a, Roser Torra16a, Serhan Tuglular17a, Priya EDTA, the Dutch Kidney Foundation, Baxter and Sandoz.
Vart6b,18b, Christoph Wanner19a, Ron T. Gansevoort6ab None of these organizations had any role in the conception or
1a
Department Nephrology, Fundacion Jimenez Diaz, Madrid, writing of this article. A.O., R.T. and M.J.S. are supported by
Spain. RETIC REDINREN RD016/0009 FEDER FUNDS from El
2a
Department of Health Sciences, University of Milan, Renal Instituto de Salud Carlos III.
Division, ASST Santi Paolo e Carlo, Milan, Italy.
3b
Department of Nephrology, Radboud University Medical
Center, Nijmegen, the Netherlands.
4a
Internal Medicine IV, Renal and Hypertensive Disease, AUTHORS’ CONTRIBUTIONS
University Medical Center, Homburg, Saar, Germany. This article was conceptualized by A.O. and R.T.G., who also
5a
Department of Nephrology, Dialysis, Nutrition, Centre wrote the first draft of the manuscript. All co-authors were in-
Hospitalier Lyon Sud, Pierre Benite Cedex, France. volved with revising the work and provided important intel-
6b
Department of Nephrology, University Medical Center lectual content. All authors have seen and approved the
Groningen, University Hospital Groningen, Groningen, the submitted version of the manuscript and agreed to be ac-
Netherlands. countable for all aspects of the work.

Chronic kidney disease key risk factor for COVID-19 93

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94 ERA-EDTA Council and the ERACODA Working Group