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Acute Kidney Injury (AKI) is an often neglected but crucial element of clinical nephrology. The aim of the Nephrology Public Policy Committee (NPPC) of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) is to promote several key aspects of European nephrology. One of the targets proposed by NPPC was to advance European nephrology involvement in AKI. We undertook literature analyses to define the current position of European nephrology in the field of AKI compared to other regions, and about how different European countries compare to each other. It appeared that vis-à-vis countries with a comparable socioeconomic status (the US, Australia, New Zealand, Canada), the European contribution was almost 50% lower. Within Europe, Central/Eastern Europe and countries with a lower gross domestic product (GDP) showed lower scientific output. Nephrologists contributed to less than half of the output. There was no trend for a change over the last decade. It is concluded that there is room to improve the contribution of European nephrology in the field of AKI. We propose a model on how to promote clinical collaboration on AKI across Europe, the creation of a pan-European nephrology network of interested units is proposed, to improve clinical outcomes, increase nephrologist involvement and awareness outside nephrology, and stimulate research on AKI in Europe. Accordingly, we also propose a list of research priorities and stress the need for more European funding of AKI research.
EDTAKI: a Nephrology and Public Policy Committee platform
call for more European involvement in acute kidney injury
Raymond Vanholder
, Eric Rondeau
, Hans-Joachim Anders
, Nicholas Carlson
, Danilo Fliser
Mehmet Kanbay
, Jose´ Anto´nio Lopes
, Patrick T. Murray
, Alberto Ortiz
, Ana B. Sanz
Nicholas M. Selby
, Andrzej Wiecek
and Ziad A. Massy
Department of Internal Medicine and Pediatrics, Nephrology Section, Ghent University Hospital, Ghent, Belgium,
European Kidney Health
Alliance, Brussels, Belgium,
Renal Intensive Care and Transplantation Unit, Hoˆpital Tenon, l’Assistance Publique-Hoˆ pitaux de Paris, Sorbonne
Universite´, Paris, France,
Department of Medicine IV, Division of Nephrology, Ludwig Maximilian University Hospital, Munich, Germany,
Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark,
Department of Research, Danish Heart
Foundation, Copenhagen, Denmark,
Internal MedicineIV, Saarland University Medical Center, Homburg, Germany,
Department of Internal
Medicine, Nephrology Section, Koc University School of Medicine, Istanbul, Turkey,
Division of Nephrology and Renal Transplantation,
Centro Hospitalar Universita´rio Lisboa Norte, Lisboa, Portugal,
School of Medicine, University College Dublin, Catherine McAuley Education
and Research Centre, Dublin, Ireland,
Research Institute Fundacion Jemenez Diaz, Autonoma University Madrid, Madrid, Spain,
Division of
Health Sciences and Graduate Entry Medicine, Centre for Kidney Research and Innovation, University of Nottingham, Nottingham, UK,
Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland,
Department of
Nephrology, Ambroise Pare´ University Hospital, l’AssistancePublique-Hoˆpitaux de Paris, Paris, France and
Centre for Research in
Epidemiology and Population Health, Paris-Saclay University, Versailles Saint Quentin University, INSERM UMRS 1018, Paris, France
Twitter handles: @EKHA_EU and @ERAEDTA
Correspondence to: Raymond Vanholder; E-mail:
Background. Acute kidney injury (AKI) is an often neglected
but crucial element of clinical nephrology. The aim of the
Nephrology and Public Policy Committee (NPPC) of the
European Renal Association–European Dialysis and Transplant
Association is to promote several key aspects of European ne-
phrology. One of the targets proposed by the NPPC was to ad-
vance European nephrology involvement in AKI.
Methods. We undertook a literature analysis to define the cur-
rent position of European nephrology in the field of AKI com-
pared with other regions and to determine how different
European countries compare with each other.
Results. It appeared that vis-a`-vis countries with a comparable
socio-economic status (the USA, Australia, New Zealand and
Canada), the European contribution was almost 50% less.
Within Europe, Central and Eastern Europe and countries with
a lower gross domestic product showed lower scientific output.
Nephrologists contributed to less than half of the output. There
was no trend of a change over the last decade.
Conclusions. There is room to improve the contribution of
European nephrology in the field of AKI. We propose a model
on how to promote clinical collaboration on AKI across Europe
and the creation of a pan-European nephrology network of in-
terested units to improve clinical outcomes, increase nephrolo-
gist involvement and awareness outside nephrology and
stimulate research on AKI in Europe. Accordingly, we also pro-
pose a list of research priorities and stress the need for more
European funding of AKI research.
Keywords: acute kidney injury, AKI, Nephrology and Public
Policy Committee, networking, NPPC
Until the beginning of this century, at least 30 definitions of
acute kidney injury (AKI) were in use [1,2]. The introduction
of classification systems, although not perfect, resulted in a
more systematic approach, acknowledging that minor changes
in kidney function are related to worse outcomes [3].
Nevertheless, AKI is not one disease but an amalgam involving
many specialties, with a broad spectrum of causes, including
hypovolaemia, hypoperfusion, nephrotoxicity, haem pigments,
intravascular coagulation, inflammation, post-renal obstruction
[4] and conditions where several factors coincide, like sepsis [5,
6]. The two most involved specialties are nephrology and inten-
sive care medicine [7]. The nephrologist’s role, although consid-
ered essential [8], may vary depending on the local situation.
Traditionally chronic kidney disease (CKD) and AKI were
viewed as separate entities, but recent knowledge considers the
two conditions as intertwined [9]. If the acute condition evolves
CThe Author(s) 2021. Published byOxford University Press on behalf of ERA-EDTA. All rights reserved.
Nephrol Dial Transplant (2021) 1–9
doi: 10.1093/ndt/gfab018
Advance Access publication 2 February 2021
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into CKD and long-term kidney replacement therapy, this
heavily weighs on prognosis, and even more so in countries
with limited resources.
The risk of AKI is increased by the presence of comorbid-
ities, including diabetes mellitus, congestive heart failure, arte-
rial hypertension, cardiovascular disease, chronic obstructive
pulmonary disease, secondary immune deficient states like
HIV, chronic liver disease, cancer and CKD [10,11]. Not coin-
cidentally, the non-communicable (chronic) diseases in this list
are also linked to CKD development [12]. The increasing
survival with most of these comorbidities also widens the time
window over which patients are susceptible to AKI [13]. Also,
the progressively growing fraction of elderly people [14]isat
increased risk of AKI and the need for KRT in case of AKI [15].
The epidemiology and phenotypes of AKI patients differ be-
tween high-income countries (HICs) and low- to middle-in-
come countries (LMICs) [4,10,16], which also applies to
Europe, as European countries belong to both categories [17].
Global warming may promote further shifts in epidemiology,
especially in southern Europe, by increasing the risk of
dehydration and infectious diseases such as malaria and dengue
Current status
The burden of AKI is immense due to its immediate conse-
quences as well as the increased risk of long-term problems
such as cardiovascular events in survivors [20]. Even mild AKI
is associated with a reduction in survival, which remains present
even if kidney function recovers [21]. These problems are asso-
ciated with a health-economic and societal burden, owing to
the severity of disease, the multiple comorbidities and compli-
cations, the need for highly technological interventions
(dialysis, artificial ventilation, close monitoring, haemodynamic
support, major surgery etc.) and lengthy recovery periods [22,
23]. They also raise ethical questions on who to treat and who
not [24].
The recent global increase in awareness and action with
regards to AKI can to a substantial extent be attributed to the
International Society of Nephrology, which launched in 2015
the ambitious 0by25 initiative (0 preventable deaths due to AKI
worldwide by 2025) [25]. Although this action mainly aimed at
improving the situation in LMICs, it applies to HICs as well,
and AKI was recently identified as an important target for the
Western European nephrology community [26].
In the context of its key role in clinical nephrology and re-
search, the European Renal Association–European Dialysis and
Transplant Association (ERA-EDTA) convened several stake-
holders in the Nephrology and Public Policy Committee
(NPPC) to consider future avenues advancing European clinical
kidney research. The NPPC defined eight topics to stimulate re-
search collaboration and grant applications in Europe and de-
cided to translate this plan into public policy action [27]. One of
the selected topics was to ‘extend understanding of AKI pro-
gression and complications’. The question arising in this con-
text is where Europe and European academia are positioned in
the fight against AKI and its consequences. Some may perceive
that Europe is lagging behind, but objective pan-European data
on this assumption are lacking.
To answer this question, we reviewed the available literature
to assess European involvement in AKI compared with other
regions worldwide and especially compared with countries with
a similar economic or scientific stature, such as the USA,
Australia–New Zealand (ANZ) and Canada. Based on these
What is already known about this subject?
Acute kidney injury (AKI) is an important kidney problem with high mortality that often receives insufficient
AKI is one of the key issues proposed for promotion by the Nephrology and Public Policy Committee of the
European Renal Association–European Dialysis and Transplant Association.
The contribution of European nephrology to AKI expertise remains unclear.
What this study adds?
The European contribution to AKI publications is low compared with other regions with similar wealth.
In European countries, there is an East–West gradient but also a low–high income gradient.
There is no trend for a change over time.
Nephrologists contributed to less than half of the publications.
What impact this may have on practice or policy?
This is a wake-up call for European nephrology to join efforts to combat AKI.
We propose a pan-European network of interested units participating in multicentric registration and research.
We recommend a model with variable involvement depending on the interest.
We also include a list of research priorities.
2R. Vanholder et al.
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data, we propose a model on how to promote clinical collabora-
tion and nephrology networking on AKI across Europe.
Literature analysis—methods
We first undertook an Endnote search for the entire year
2018 with key terms ‘acute kidney injury’ or ‘acute renal failure’
in the title (referred to by the aggregated term ‘AKI’ in what fol-
lows). As this analysis was started in 2019, the year 2018 was se-
lected, as it was the most recent year with complete literature
data. Experimental and clinical studies and case reports were in-
cluded. We excluded publications that were not directly on AKI
(e.g. papers on acute graft rejection) and letters and comments.
Papers were not excluded based on language or quality criteria.
We recorded the nationality of the first author as representative
for the origin of the publications.
We first performed an analysis of the absolute number of
publications on AKI per region, either a continent, part of a
continent (Latin America and ANZ), a group of countries (the
non-European Mediterranean countries) or an individual coun-
try (USA and Canada). We then normalized these data per mil-
lion population (pmp), which we used as a surrogate for the
human resource capacity to perform scientific and/or clinical
analyses. The non-European Mediterranean countries were
considered as a separate geographic entity because their physi-
cians and researchers are eligible for ERA-EDTA membership.
One of the major questions was the relative scientific output
of Europe versus the USA, the other large Western entity with
vested research interests. To exclude the possibility of a general
trend for a different European kidney research endeavour ver-
sus the USA, we performed a similar scientific output analysis
with search terms ‘chronic kidney disease’ and two more re-
stricted nephrology topics where specific European networks
are active: ‘uremic toxins’ (EUTox) and ‘hemolytic uremic syn-
drome’ (HUS; ERKNet). The ratio of the number of publica-
tions for Europe versus the USA for AKI was compared with
that for the three other topics. We also calculated the mean im-
pact factor of the journals in which the analysed publications
We then ranked all European countries (except those with
<100 000 inhabitants) for the number of generated AKI publi-
cations pmp. We also performed subanalyses comparing
Western and Central and Eastern Europe and the highest,
middle and lowest tertiles of countries classified based on their
gross domestic product (GDP) pmp. Central and Eastern
Europe was defined as the geographic area that was formerly
under communist political influence (former Soviet Union,
Warsaw Pact countries and Yugoslavia and Albania) plus
Turkey. GDP was expressed in US dollars as provided by
Worldometer [28].
The above comprehensive 1-year analysis did not permit as-
sessment of the evolution over time. To answer this question, in
a second, more restricted investigation we assessed the number
of publications with the acronym ‘AKI’ in the title (referred to
as ‘AKI in title’ in what follows) for the years 2012–19 and com-
pared the percent share of European contributions to the rest of
the world. This examination was also used to assess the contri-
bution of nephrologists vis-a`-vis other specialties in Europe and
per country. Here also, assessments were based on the national-
ity of the first author. To analyse specialty involvement, only
countries with more than four contributions in the database
were included.
The first large-scale analysis for the year 2018 comprised 1554
references. When analysing the publication rate in absolute
numbers, Asia had the highest production (564 publications),
followed by Europe (438) and the USA (362)
(Table 1; Supplementary data,Figure S1). When the publication
rate was normalized pmp, the list is headed by ANZ and the
USA (both 1.1 publications pmp) and Canada (1.01). The rate
for Europe was almost 50% lower (0.59 pmp) than that for the
USA (Table 1; Supplementary data,Figure S1).
These differences could, however, be an illustration of a gen-
eral trend for lower European activity in scientific and clinical
nephrology reporting. We therefore also compared European
activity to that of the USA for uraemic toxicity, HUS and CKD.
The ratio of European versus US production was higher for
these three topics than for AKI (Figure 1). The mean journal
impact factors for the European and US AKI papers were the
same (4.2 67.3 and 4.3 67.7).
Analysis of scientific output per European country normal-
ized pmp showed substantial differences, from 2.5 pmp
(Iceland) to 0.05 pmp (Ukraine and the Russian Federation)
(Table 2), while 12 of the 43 countries (27.9%) produced no
Table 1. Publications on AKI per region in 2018
Absolute number of
Share of total
publications (%)
Population in
Share of total
publications pmp (%)
16 1.0 1,216.0 0.01 0.1
ANZ 33 2.1 29.9 1.10 24.9
Asia 564 36.3 4,463.0 0.35 7.9
Canada 38 2.4 37.6 1.01 22.8
Europe 438 28.1 741.4 0.59 13.3
Latin America 69 4.4 626.0 0.11 2.5
Mediterranean 63 2.2 227.5
0.15 3.4
USA 362 23.3 328.2 1.10 24.9
Sub-Saharan Africa.
Total population of Syria, Lebanon, Israel, Egypt, Libya, Algeria, Tunisia and Morocco.
NPPC platform call for more European involvement in AKI 3
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publications. Of note, the scientific output list is headed by
two countries with a population 500 000, so that even a sin-
gle publication gave high scores. When countries were strati-
fied according to a scientific output of >1.00, 0.51–1.00,
0.01–0.50 and 0 pmp, a definite East–West gradient was ob-
served, with a lower scientific output in Central and Eastern
Europe (Figure 2;Table 3). This dichotomy, however, was
paralleled by marked differences in country wealth. GDP
pmp was almost 5 times higher in Western than in Central
and Eastern Europe (Table 3). Stratification of European
countries in tertiles depending on GDP pmp showed a gradi-
ent in proportion to GDP (Table 3). However, there are
exceptions to this trend, essentially corresponding to smaller
countries (Slovenia in the middle GDP tertile with a publica-
tion rate of 1.43 pmp and Croatia in the upper part of the
lower GDP tertile with 0.98).
The longitudinal analysis based on inclusion of the acronym
AKI in the publication title (2012–19) included 213 publica-
tions. It showed an unmodified share of European
contributions versus the rest of the world in the range of
20–30% over the entire period under consideration (Figure 3;
Supplementary data,Table S1). With all data taken together,
the share of nephrologists as first author was slightly <50%,
whereas other specialists, mainly intensive care physicians, con-
tributed to the remaining half (Figure 4). Considering individ-
ual countries with four or more publications, there were
marked differences in contributions from nephrologists,
ranging from the majority of contributions by nephrologists
(Germany, Spain and Italy) to only a minority (the Netherlands
and France) (Supplementary data,Table S2).
FIGURE 2: European publication rate on AKI in 2018 per country
normalized pmp. Darkness of shade in proportion to publication
rate (darkest for highest rate). Rates were calculated as the number
of publications on AKI based on AKI in the title. Blue colours: publi-
cation rate >1.00 pmp, 0.51–1.00 pmp, 0.01–0.50 pmp. Grey: publi-
cation rate 0. There is a marked East–West gradient.
Table 2. European publication rate on AKI in 2018 per country normal-
ized pmp
Country Publications, nPopulation
pmp, n
Iceland 1 0.4 2.50
Malta 1 0.5 2.00
Switzerland 13 8.5 1.53
Slovenia 3 2.1 1.43
Denmark 8 5.8 1.38
The Netherlands 23 17.4 1.32
Belgium 15 11.4 1.32
Finland 6 5.5 1.09
Portugal 11 10.3 1.07
Italy 63 60.4 1.04
Croatia 4 4.1 0.98
Austria 8 8.9 0.90
UK 59 66.4 0.89
Cyprus 1 1.2 0.83
Sweden 8 10.1 0.79
Greece 8 10.3 0.78
Spain 34 46.7 0.73
Germany 60 82.9 0.72
France 45 67.1 0.67
Ireland 3 4.9 0.61
North Macedonia 1 2.1 0.48
Poland 15 38.4 0.39
Norway 2 5.3 0.38
Slovak Republic 2 5.4 0.37
Lithuania 1 2.8 0.36
Turkey 29 83.1 0.35
Georgia 1 3.7 0.27
Romania 3 19.5 0.15
Serbia 1 7.0 0.14
8 145.9 0.05
Ukraine 2 41.7 0.05
Small countries (<100 000 inhabitants) like Andorra, Liechtenstein, Monaco, San
Marino and the Vatican were not included. No publications for Albania, Belarus,
Bosnia-Herzegovina, Bulgaria, Czech Republic, Estonia, Hungary, Kosovo, Latvia,
Luxembourg, Moldova and Montenegro.
Ratio Europe/USA
FIGURE 1: Ratio of the number of publications in Europe versus the
USA for AKI, CKD, HUS and uraemic toxins (Utox) 2018.
4R. Vanholder et al.
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This study analysed the European contribution to both basic and
clinical AKI research as compared with other regions and made
an internal comparison within Europe. The principal findings are:
(i) Normalized to pmp inhabitants, the European contribu-
tion to AKI research is substantially smaller than that of
regions with a similar socio-economic status, such as
North America or ANZA.
(ii) The discrepancy versus the USA was not observed for
other nephrology research topics, such as HUS, uraemic
toxicity or CKD. These differences are not paralleled by
the mean of the impact factors of the journals in which
the papers appeared.
(iii) A manifest East–West gradient in scientific output exists
and this trend parallels disparities in country wealth.
(iv) The contribution of nephrology to European AKI publi-
cations is <50%, with intensive care medicine as an al-
most equivalent contributing specialty.
(v) There is no signal of change in European activity over
the past decade.
The relatively low contribution of European nephrology to
AKI research is worrisome in view of the clinical and health-
economic burden of AKI [20]. In addition, contributing factors
to the incidence of this condition will very likely gain in impor-
tance in the future due to the aging population [24] and im-
proved outcomes of other associated conditions such as
cardiovascular disease [29,30] and cancer [31]. Also, related
costs are projected to increase [22]. Hence research in this field
is essential for the medical community, patients and society
alike. It would be unfavourable for Europe not to be in the front
line of unravelling the pathophysiology of and searching for
new cures for AKI, as a backlog in progress would force
European nephrology to largely depend on non-European data
and therapeutic solutions.
Some may argue that the scanty European contribution in
AKI is emblematic of a global lack of European interest in
kidney research. However, this assumption is not mirrored
for other nephrology topics, and especially not for areas where
European networks like EUTox or ERKNET are active
(Figure 1). Likewise, one may argue that if the analysis had been
limited to Western Europe, scientific output would have been
closer to that from the USA, Canada or ANZ. However, it
would be unlikely for scientific output in those countries to be
geographically more homogeneous than it is in Europe. In addi-
tion, for policy action and improvement initiatives, it is prefera-
ble to consider the European Union and Europe as one entity.
Finally, even if the first author is not European, Europeans
might be ranked as co-authors. However, we thought that the
first author is in most cases the most important contributor to a
publication, reflecting the place where the analysis, observations
or study took place, and in addition they most often are junior
staff members, who constitute the future of medical interest in a
given topic, in this case AKI.
The essential role of the nephrologist in AKI has repeatedly
been emphasized [9,32,33]. First, not all AKI cases are in need
of critical care, and in those patients the nephrologist may be
crucial for timely identification of the problem and its causes
and for instituting therapy, as well as playing an educational role
and raising awareness among non-nephrologists and non-AKI
physicians. Also, in ICU patients, the causes may not be the
more usual critical conditions, like sepsis or kidney hypoperfu-
sion, but intrinsic kidney disorders for which nephrologists can
Table 3. Relation between scientific output (publications on the topic of AKI in 2018) and geographic location and GDP
Region West/East (number
of countries)
GDP pmp
mean 6SD
GDP pmp
median (range)
Scientific output,
mean 6SD
Scientific output,
median (range)
Western Europe 20/0 48 640 622 256 42 229 (105 280–18 695) 1.03 60.54 0.90 (2.50–0)
Central and Eastern Europe 0/21 9877 66119
9198 (23 488–2002) 0.20 60.36
0 (1.43–0)
GDP pmp
Highest tertile 14/0 58 513 618 561 51 436 (105 280–39 532) 1.01 60.58 0.9 (2.50–0)
Middle tertile 6/8 20 720 65345 19 692 (32 038–13 871) 0.64 60.58 0.65 (2.00–0)
Lowest tertile 0/15 6641 63273 5418 (13 200–2002) 0.16 60.26
0.05 (0.98–0)
Scientific output was calculated as the number of publications pmp. GDP: gross domestic product; pmp: per million population.
*P <0.001 versus West.
**P <0.01 versus West.
***P <0.01 versus highest tertile.
2012 2013 2014 2015 2016 2017 2018 2019 Overall
% Publications
FIGURE 3: Year-by-year European contribution to publications on
AKI (% of publications out of overall worldwide publications, based
on AKI in title). There was no significant trend.
NPPC platform call for more European involvement in AKI 5
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be instrumental in diagnosis and management. In addition,
nephrologists can advise on correction of electrolyte disorders
[32] and interpretation of serum creatinine [34]. Second, neph-
rologists master a broad spectrum of kidney replacement thera-
pies, including intermittent and extended haemodialysis and
peritoneal dialysis [35], which may help in overwhelmed health-
care systems like during the ongoing coronavirus disease 2019
(COVID-19) pandemic [36]. Third, nephrologists may assist in
avoiding futile therapy, e.g. in frail AKI patients [24,32,37].
Fourth, and above all, in view of the frequent link with CKD, the
nephrologist can play a role in preventing evolution towards
CKD and to steer the approach and follow-up if kidney function
does not recover [9,38,39]. Thus we call not only for European
research activity on AKI, but also for clinical involvement of
nephrologists in AKI outside the nephrology unit.
Unfortunately, if the publication activity as illustrated in this
study is representative of the clinical involvement of nephrolo-
gists, our data suggest ample room for increasing this participa-
tion. In contrast, more commitment will increase the visibility of
nephrology regarding AKI. As the relation with other specialties
might differ between countries and hospitals, mapping of the
current situation might be of interest.
The representation of intensive care unit (ICU) specialists in
the AKI literature does not reflect the actual epidemiology of
AKI in hospitals and is likely biasing understanding of AKI. In
a recent European study from a single tertiary hospital, based
on electronic screening of patient records using Kidney Disease:
Improving Global Outcomes criteria, ICU cases accounted for
only 3% of hospital-acquired AKI [40]. Of note, this analysis is
based on a single centre and the situation might differ in
settings with different healthcare systems or patient mixes. In
addition, the study contained but was by definition not limited
to ICU patients, but in this way exactly stresses that AKI is also
frequent outside the ICU.
The recent COVID-19 pandemic illustrates several of the
concerns raised above. The frequent presence of cytokine storm
suggested a high propensity for AKI [41] and the many negative
facets of AKI, such as the high complication rate, mortality and
technical demands, emerging in a time-condensed way, while
AKI appeared to be a major complication in many of the most
severely affected COVID-19 patients [4245]. However, espe-
cially in the early phase of the pandemic, European nephrology
needed to rely on epidemiologic data from China [46]orthe
USA [47], although the first cases in Europe and the USA were
reported almost simultaneously [48,49]. The ERA-EDTA took
the laudable decision to open a registry on COVID-19 and its
links to kidney disease (ERACODA) [50,51], but to the best of
our knowledge, this database remained limited to dialysis
patients and transplant recipients.
To improve this situation and boost the European contribu-
tion to AKI, we propose the development of a European ne-
phrology network of clinicians and researchers with interest in
AKI. For each country, one or more coordinators are invited to
convene interested groups in their regional/national environ-
ment. Networks are among the tools to advance interest, knowl-
edge and outcomes in AKI [52] and exist already in some
European countries like the UK [53] and France [54], but they
should be rolled out on a broad European level, e.g. by applying
for a European Cooperation in Science and Technology action.
Once installed, participants will be offered the opportunity to
contribute to European registration and research projects and
proposals for European Union support via Framework
Programmes like Horizon Europe [55]. Some initiatives may be
global and include a broad array of participants; others may be
restricted to a few interested parties, applying a model similar
to that of the EUTox Work Group [56,57]. The network could
also be instrumental in developing pan-European projects to
improve clinical outcomes, such as developing a uniform labo-
ratory AKI alert system, preferably inspired by existing systems
[58]. However, networking may not be the only solution. An
additional focus point could be the extension of involvement of
nephrologists in AKI outside nephrology (intensive care, but
also other specialties like oncology, cardiology, surgery etc.). A
European network could also play a crucial coordinating role in
promoting and organizing this evolution.
The group should define its immediate and long-term re-
search priorities. A preliminary, non-exhaustive list of such
topics can be found in Table 4.
The lower participation in Central and Eastern Europe
should not be considered as a symptom of lack of interest or
quality care, but the parallelism with GDP is striking. We can
only speculate on the reasons, but a probable role can be attrib-
uted to fewer resources for research, lack of time for physicians
possibly resulting in less attention to AKI cases or, since the
number of nephrologists is lower in Central and Eastern than in
Western Europe [59], lower specialist numbers. We plead for
active involvement of Central and Eastern Europe, especially
since differences in epidemiology may lead to interesting obser-
vations and broader pathophysiologic diversity.
Our analysis has a number of drawbacks. First, the analysis
covered only 1 year. Countries might have achieved a different
profile in another year. It is unlikely, however, that this would
have affected the general comparisons between regions or
countries. Second, a number of references may have been
missed if the title did not contain the pre-defined keywords,
but again, this was unlikely to affect general trends. Third,
the use of the address of the first author may not always be
Intensive care
Medical unit
FIGURE 4: Percentage contribution of different specialties in
European publications with AKI in the title (2012–19).
6R. Vanholder et al.
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representative to define the country where the study was
executed. Fourth, the long-term analysis with comparisons
between specialties was based on a second, smaller database,
which might have been biased by the smaller number of re-
trieved papers, while the term AKI in the title might have
been used to a different degree depending on the year, spe-
cialty or country of origin. Finally, the lower publication rate
in Central and Eastern Europe might be attributable to a
number of publications in a local language, which may have
been missed in our search.
On the other hand, our analysis also has a number of
strengths. To our knowledge, this is the first analysis of scien-
tific output on AKI research in the European nephrology com-
munity with comparisons of aspects such as regional and
country activity, evolution over time and involved specialties
and the impact of country wealth. In addition, it was broad
enough to provide useful information on how to inform future
initiatives to modify the situation.
In conclusion, this analysis shows, compared with countries
or regions with comparable socio-economic stature, a relative
lack of European initiatives to study and report on clinical
observations with regards to AKI. As for other focus areas de-
fined by the NPPC, Central and Eastern European and low-
income countries appear to demand special consideration [60].
The data also underscore that the involvement of nephrologists
in this domain could be improved. The fact that only one au-
thor of this article is a woman suggests that there is also room
for more involvement of women. More time could be devoted
to AKI in European nephrology conferences (in the recent
ERA-EDTA meetings markedly more slots were devoted to
CKD than to AKI) and in continuing medical education
courses, especially in LMICs. Furthermore, increased focus on
AKI in European research programmes with more funding for
AKI studies is another necessity. To cope with these problems,
a European nephrology network of researchers and clinicians
interested in AKI will be created under the auspices of ERA-
EDTA, with the intent to inspire interest in AKI and to develop
common research projects.
Supplementary data are available at ndt online.
H.J.A. reports personal fees from Secarna; grants and personal
fees from Previpharma and personal fees from Novartis, Bayer,
GlaxoSmithKline, Boehringer and AstraZeneca, outside the sub-
mitted work. P.T.M. reports personal fees from AM-Pharma,
FAST Biomedical and Renibus Therapeutics, outside the sub-
mitted work. A.O. reports grants from Servier, Sanofi and
Mundipharma and personal fees from Sanofi, Amgen,
AstraZeneca, Otsuka and Kyowa, outside the submitted work.
E.R. reports grants, personal fees and non-financial support
from Alexion Pharmaceuticals, outside the submitted work.
None of the remaining authors declared any conflicts of interest.
The data underlying this article are available in the article and
in its online supplementary material.
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Perform interventional trials of prevention or treatment of AKI
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Describe the impact of primary and secondary preventive measures on
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NPPC platform call for more European involvement in AKI 9
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Full-text available
Chronic kidney disease (CKD) is a major health problem because of its high prevalence, associated complications and high treatment costs. Several aspects of CKD differ significantly in the Eastern European nephrology community compared with Western Europe because of different geographic, socio-economic, infrastructure, cultural and educational features. The two most frequent aetiologies of CKD, DM and hypertension, and many other predisposing factors, are more frequent in the Eastern region, resulting in more prevalent CKD Stages 3–5. Interventions may minimize the potential drawbacks of the high prevalence of CKD in Eastern Europe, which include several options at various stages of the disease, such as raising public, medical personnel and healthcare authorities awareness; early detection by screening high-risk populations; preventing progression and CKD-related complications by training health professionals and patients; promoting transplantation or home dialysis as the preferred modality; disseminating and implementing guidelines and guided therapy and encouraging/supporting country-specific observational research as well as international collaborative projects. Specific ways to significantly impact CKD-related problems in every region of Europe through education, science and networking are collaboration with non-nephrology European societies who have a common interest in CKD and its associated complications, representation through an advisory role within nephrology via national nephrology societies, contributing to the training of local nephrologists and stimulating patient-oriented research. The latter is mandatory to identify country-specific kidney disease–related priorities. Active involvement of patients in this research via collaboration with the European Kidney Patient Federation or national patient federations is imperative to ensure that projects reflect specific patient needs.
Full-text available
Background. Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. Methods. We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. Results. Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 ± 13 and 67 ± 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3–30.2%] in kidney transplant and 25.0% (95% CI 20.2–30.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59–1.10, P = 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n = 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation <1 year before presentation (HR adjusted for sex, age and frailty 0.20, 95% CI 0.07–0.56, P < 0.01). Conclusions. The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients.
Full-text available
Background Predictive models and clinical risk scores for hospital-acquired acute kidney injury (AKI) are mainly focused on critical and surgical patients. We have used the electronic clinical records from a tertiary care general hospital to develop a risk score for new-onset AKI in general inpatients that can be estimated automatically from clinical records. Methods A total of 47 466 patients met inclusion criteria within a 2-year period. Of these, 2385 (5.0%) developed hospital-acquired AKI. Step-wise regression modelling and Bayesian model averaging were used to develop the Madrid Acute Kidney Injury Prediction Score (MAKIPS), which contains 23 variables, all obtainable automatically from electronic clinical records at admission. Bootstrap resampling was employed for internal validation. To optimize calibration, a penalized logistic regression model was estimated by the least absolute shrinkage and selection operator (lasso) method of coefficient shrinkage after estimation. Results The area under the curve of the receiver operating characteristic curve of the MAKIPS score to predict hospital-acquired AKI at admission was 0.811. Among individual variables, the highest odds ratios, all >2.5, for hospital-acquired AKI were conferred by abdominal, cardiovascular or urological surgery followed by congestive heart failure. An online tool ( will facilitate validation in other hospital environments. Conclusions MAKIPS is a new risk score to predict the risk of hospital-acquired AKI, based on variables present at admission in the electronic clinical records. This may help to identify patients who require specific monitoring because of a high risk of AKI.
Full-text available
The kidney is not typically the main target of severe acute respiratory syndrome coronavirus 2, but surprisingly, acute kidney injury (AKI) may occur in 4-23% of cases, whereas the dialysis management of AKI from coronavirus 2019 has not gained much attention. The severity of the pandemic has resulted in significant shortages in medical supplies, including respirators, ventilators and personal protective equipment. Peritoneal dialysis (PD) remains available and has been used in clinical practice for AKI for >70 years; however, it has been used on only a limited basis and therefore experience and knowledge of its use has gradually vanished, leaving a considerable gap. The turning point came in 2007, with a series of sequential publications providing solid evidence that PD is a viable option. As there was an availability constraint and a capacity limit of equipment/supplies in many countries, hemodialysis and convective therapies became alternatives. However, even these therapies are not available in many countries and their capacity is being pushed to the limit in many cities. Evidence-based PD experience lends support for the use of PD now.
Full-text available
The American Society of Nephrology, the European Renal Association–European Dialysis and Transplant Association and the International Society of Nephrology Joint Working Group on Ethical Issues in Nephrology have identified ten broad areas of ethical concern as priority challenges that require collaborative action. Here, we describe these challenges — equity in access to kidney failure care, avoiding futile dialysis, reducing dialysis costs, shared decision-making in kidney failure care, living donor risk evaluation and decision-making, priority setting in kidney disease prevention and care, the ethical implications of genetic kidney diseases, responsible advocacy for kidney health and management of conflicts of interest — with the aim of highlighting the need for ethical analysis of specific issues, as well as for the development of tools and training to support clinicians who treat patients with kidney disease in practising ethically and contributing to ethical policy-making.
The rate of acute kidney injury (AKI) associated with patients hospitalized with Covid-19, and associated outcomes are not well understood. This study describes the presentation, risk factors and outcomes of AKI in patients hospitalized with Covid-19. We reviewed the health records for all patients hospitalized with Covid-19 between March 1, and April 5, 2020, at 13 academic and community hospitals in metropolitan New York. Patients younger than 18 years of age, with end stage kidney disease or with a kidney transplant were excluded. AKI was defined according to KDIGO criteria. Of 5,449 patients admitted with Covid-19, AKI developed in 1,993 (36.6%). The peak stages of AKI were stage 1 in 46.5%, stage 2 in 22.4% and stage 3 in 31.1%. Of these, 14.3% required renal replacement therapy (RRT). AKI was primarily seen in Covid-19 patients with respiratory failure, with 89.7% of patients on mechanical ventilation developing AKI compared to 21.7% of non-ventilated patients. 276/285 (96.8%) of patients requiring RRT were on ventilators. Of patients who required ventilation and developed AKI, 52.2% had the onset of AKI within 24 hours of intubation. Risk factors for AKI included older age, diabetes mellitus, cardiovascular disease, black race, hypertension and need for ventilation and vasopressor medications. Among patients with AKI, 694 died (35%), 519 (26%) were discharged and 780 (39%) were still hospitalized. AKI occurs frequently among patients with Covid-19 disease. It occurs early and in temporal association with respiratory failure and is associated with a poor prognosis.
The outbreak of coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic. Most patients with COVID-19 have mild symptoms, but about 5% develop severe symptoms, which can include acute respiratory distress syndrome, septic shock, and multiple organ failure. Kidney involvement is frequent, with clinical presentation ranging from mild proteinuria to progressive acute kidney injury (AKI) necessitating renal replacement therapy (RRT). An understanding of the pathophysiology and mechanisms of kidney damage and AKI in the setting of critical illness and COVID-19 is emerging, although further research is needed to identify patients at risk of AKI and to guide management strategies. As no specific treatment options exist for AKI secondary to COVID-19, intensive care is largely supportive. Current approaches to prevention and management of AKI, and identification of potential indications for use of RRT and sequential extracorporeal therapies, are based mainly on clinical experience, and AKI strategies are adapted empirically to patients with COVID-19. International collaborative and cross-disciplinary research is needed to obtain adequate evidence to support current clinical approaches and to develop new approaches to management.
The most common reported reasons for intensive care unit admission for patients with severe coronavirus disease 2019 (COVID-19) are either hypoxemic respiratory failure leading to mechanical ventilation or hypotension requiring vasopressor support. Data on AKI are either lacking¹ or only reporting incidence on the basis of case series and retrospective studies.² In this Perspective, we emphasize that AKI can be a severe complication of COVID-19 and highlight the importance of assessing, defining, and reporting the course of AKI.
Background: Some patients with COVID-19 pneumonia also present with kidney injury, and autopsy findings of patients who died from the illness sometimes show renal damage. However, little is known about the clinical characteristics of kidney-related complications, including hematuria, proteinuria, and AKI. Methods: In this retrospective, single-center study in China, we analyzed data from electronic medical records of 333 hospitalized patients with COVID-19 pneumonia, including information about clinical, laboratory, radiologic, and other characteristics, as well as information about renal outcomes. Results: We found that 251 of the 333 patients (75.4%) had abnormal urine dipstick tests or AKI. Of 198 patients with renal involvement for the median duration of 12 days, 118 (59.6%) experienced remission of pneumonia during this period, and 111 of 162 (68.5%) patients experienced remission of proteinuria. Among 35 patients who developed AKI (with AKI identified by criteria expanded somewhat beyond the 2012 Kidney Disease: Improving Global Outcomes definition), 16 (45.7%) experienced complete recovery of kidney function. We suspect that most AKI cases were intrinsic AKI. Patients with renal involvement had higher overall mortality compared with those without renal involvement (28 of 251 [11.2%] versus one of 82 [1.2%], respectively). Stepwise multivariate binary logistic regression analyses showed that severity of pneumonia was the risk factor most commonly associated with lower odds of proteinuric or hematuric remission and recovery from AKI. Conclusions: Renal abnormalities occurred in the majority of patients with COVID-19 pneumonia. Although proteinuria, hematuria, and AKI often resolved in such patients within 3 weeks after the onset of symptoms, renal complications in COVID-19 were associated with higher mortality.