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Aims: The objective of the present study is to assess the prognostic value of acute kidney injury (AKI) in the evolution of patients with heart failure (HF) using real-world data. Methods and results: Patients with a diagnosis of HF and with serial measurements of renal function collected throughout the study period were included. Estimated glomerular filtration rate (GFR) was calculated with the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). AKI was defined when a sudden drop in creatinine with posterior recovery was recorded. According to the Risk, Injury, Failure, Loss, and End-Stage Renal Disease (RIFLE) scale, AKI severity was graded in three categories: risk [1.5-fold increase in serum creatinine (sCr)], injury (2.0-fold increase in sCr), and failure (3.0-fold increase in sCr or sCr > 4.0 mg/dL). AKI incidence and risk of hospitalization and mortality after the first episode were calculated by adjusting for potential confounders. A total of 30 529 patients with HF were included. During an average follow-up of 3.2 years, 5294 AKI episodes in 3970 patients (13.0%) and incidence of 3.3/100 HF patients/year were recorded. One episode was observed in 3161 (10.4%), two in 537 (1.8%), and three or more in 272 (0.9%). They were more frequent in women with diabetes and hypertension. The incidence increases across the GFR levels (Stages 1 to 4: risk 7.6%, 6.8%, 11.3%, and 12.5%; injury 2.1%, 2.0%, 3.3%, and 5.5%; and failure 0.9%, 0.6%. 1.4%, and 8.0%). A total of 3817 patients with acute HF admission were recorded during the follow-up, with incidence of 38.4/100 HF patients/year, 3101 (81.2%) patients without AKI, 545 (14.3%) patients with one episode, and 171 (4.5%) patients with two or more. The number of AKI episodes [one hazard ratio (HR) 1.05 (0.98-1.13); two or more HR 2.01 (1.79-2.25)] and severity [risk HR 1.05 (0.97-1.04); injury HR 1.41 (1.24-1.60); and failure HR 1.90 (1.64-2.20)] increases the risk of hospitalization. A total of 10 560 deaths were recorded, with incidence of 9.3/100 HF patients/year, 8951 (33.7%) of subjects without AKI episodes, 1180 (11.17%) of subjects with one episode, and 429 (4.06%) with two or more episodes. The number of episodes [one HR 1.05 (0.98-1.13); two or more HR 2.01 (1.79-2.25)] and severity [risk 1.05 confidence interval (CI) (0.97-1.14), injury 1.41 (CI 1.24-1.60), and failure 1.90 (CI 1.64-2.20)] increases mortality risk. Conclusions: The study demonstrated the worse prognostic value of sudden renal function decline in HF patients and pointed to those with more future risk who require review of treatment and closer follow-up.
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Acute kidney injury in heart failure: a population study
Jose Luis Holgado
, Cristina Lopez
, Antonio Fernandez
, Inmaculada Sauri
, Ruth Uso
, Jose Luis Trillo
, Sara
, Julio Nuñez
, Josep Redon
*and Adrian Ruiz
Cardiovascular and Renal Research Group, INCLIVA Research Institute, University of Valencia, Avda Blasco Ibañez,
, Valencia, Spain;
Internal Medicine Hospital,
Clínico de Valencia, Valencia, Spain;
Cardiology Hospital, Clínico de Valencia, Valencia, Spain;
CIBERObn, Carlos III Health Institute, Madrid, Spain
Aims The objective of the present study is to assess the prognostic value of acute kidney injury (AKI) in the evolution of
patients with heart failure (HF) using real-world data.
Methods and results Patients with a diagnosis of HF and with serial measurements of renal function collected throughout
the study period were included. Estimated glomerular ltration rate (GFR) was calculated with the CKD-EPI (Chronic Kidney
Disease Epidemiology Collaboration). AKI was dened when a sudden drop in creatinine with posterior recovery was recorded.
According to the Risk, Injury, Failure, Loss, and End-Stage Renal Disease (RIFLE) scale, AKI severity was graded in three cate-
gories: risk [1.5-fold increase in serum creatinine (sCr)], injury (2.0-fold increase in sCr), and failure (3.0-fold increase in sCr
or sCr >4.0mg/dL). AKI incidence and risk of hospitalization and mortality after the rst episode were calculated by adjusting
for potential confounders. A total of 30 529 patients with HF were included. During an average follow-up of 3.2years, 5294 AKI
episodes in 3970 patients (13.0%) and incidence of 3.3/100 HF patients/year were recorded. One episode was observed in
3161 (10.4%), two in 537 (1.8%), and three or more in 272 (0.9%). They were more frequent in women with diabetes and hy-
pertension. The incidence increases across the GFR levels (Stages 1to 4:risk 7.6%, 6.8%, 11.3%, and 12.5%; injury 2.1%, 2.0%,
3.3%, and 5.5%; and failure 0.9%, 0.6%. 1.4%, and 8.0%). A total of 3817 patients with acute HF admission were recorded dur-
ing the follow-up, with incidence of 38.4/100 HF patients/year, 3101 (81.2%) patients without AKI, 545 (14.3%) patients with
one episode, and 171 (4.5%) patients with two or more. The number of AKI episodes [one hazard ratio (HR) 1.05 (0.981.13);
two or more HR 2.01 (1.792.25)] and severity [risk HR 1.05 (0.971.04); injury HR 1.41 (1.241.60); and failure HR 1.90 (1.64
2.20)] increases the risk of hospitalization. A total of 10 560 deaths were recorded, with incidence of 9.3/100 HF patients/year,
8951 (33.7%) of subjects without AKI episodes, 1180 (11.17%) of subjects with one episode, and 429 (4.06%) with two or more
episodes. The number of episodes [one HR 1.05 (0.981.13); two or more HR 2.01 (1.792.25)] and severity [risk 1.05 con-
dence interval (CI) (0.971.14), injury 1.41 (CI 1.241.60), and failure 1.90 (CI 1.642.20)] increases mortality risk.
Conclusions The study demonstrated the worse prognostic value of sudden renal function decline in HF patients and pointed
to those with more future risk who require review of treatment and closer follow-up.
Keywords Heart failure; Acute kidney injury; Renal function; Risk of hospitalization; Risk of mortality
; Revised:
; Accepted:
*Correspondence to: Josep Redon, Cardiovascular and Renal Research Group, INCLIVA Research Institute, University of Valencia, Avda Blasco Ibañez,
Spain. Email:
Heart failure (HF) is a mounting condition with huge impact in
health care burden. Prevalence is still increasing mainly
driven for the aging population in which renal dysfunction is
also frequent.
The association between HF and renal dys-
function is well known; while HF increases the risk of renal in-
sufciency, chronic kidney disease (CKD) increases the risk of
hospitalization and mortality.
Thus, the term cardiorenal
syndromewith various subtypes has been introduced.
One of the cardiorenal syndromes is acute kidney injury
(AKI), a syndrome of multiple aetiologies associated with in-
creased risk of hospitalization and high mortality.
It has
been recognized that even patients who have complete or
near-complete kidney function recovery after AKI are at in-
creased risk of progressive CKD, and that superimposition of
©2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
ESC Heart Failure (2020)
Published online in Wiley Online Library ( DOI: 10.1002/ehf2.12595
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the
original work is properly cited.
AKI on CKD is associated with acceleration in the rate of pro-
gression to end-stage renal disease.
In patients with HF, the
incidence and impact of AKI have been reported mainly in
subjects hospitalized with acute HF (AHF), in which the prev-
alence of AKI is ~20%, and it has been recognized that AKI is a
strong independent predictor of both in-hospital and 1-year
A meta-analysis of cohorts, registries, and post-
hoc studies concluded that CKD and worsening of renal func-
tion (WRF),
a term that has been used instead of AKI in HF
are frequently observed in patients with HF. How-
ever, the authors acknowledge heterogeneity due to differ-
ent inclusion criteria, selection bias, and different denitions
and criteria used to qualify AKI.
Indeed, the incidence, prev-
alence, and consequences of AKI in patients with HF are not
well established.
The objective of the present study is to assess the prognos-
tic value of AKI in the evolution of patients with HF using real-
world data. This study reects the view that electronic health
record (EHR)-based studies from general practice are a repre-
sentative setting to evaluate burden of disease associated
with health conditions such as AKI in HF.
Subjects and methods
Study population and baseline data collection
The sample was recruited from beneciaries of the Valencian
Health Agencys universal health care system. The Valencian
Community is a Mediterranean region located on the east
coast of Spain, with a population of 3 799 885 people older
than 18 years in 2012. Every patient has a unique personal
identication number for the health system, so there is one
unique electronic centralized clinical record per patient. The
total population data were extracted using the health infor-
mation exchange function of ABUCASIS for the period of time
between 1January 2012 and 31 December 2015. ABUCASIS
includes information on patient demographics, medications,
vital status, past medical history, and laboratory data,
among others. Patientsdata collected from the system dur-
ing the study were documented by a process of pseudo-
anonymization, making it impossible to use this information
to identify the patients because the only link between the
data and the patient is a code not available to the re-
searchers. The data generated during the study were handled
according to the Spanish Law 3/2008 of Data Protection and
Guaranty of Digital Rights the and corresponding European
The study was reviewed and approved by the
Committee for Ethics and Clinical Trials of the Hospital Clinico
of Valencia.
In the general population, 132 065 subjects were men and
women with a diagnosis of HF (ICD
), and the eligible patients for the present study were
those with serial measurements of renal function collected
throughout the study period. Participants were included in
the study from 1January 2012 if they fullled the eligibility
condition of an HF diagnosis before this time. Subsequently,
participants newly diagnosed of HF during the study period
until 31 December 2015 were also included. Finally, 30 529
subjects of both sexes aged 18 years or older who attended
routine health examinations and fullled eligibility criteria
were initially selected from the total population database.
The observational study was undertaken as part of routine
clinical practice.
Glomerular ltration rate and acute kidney injury
Serum creatinine was measured using a kinetic rate Jaffé
method in a Hitachi Model 704 multichannel analyser
(Boehringer Mannheim Diagnostics). Serum creatinine was
calibrated to account for laboratory differences across time
and to standardize to creatinine measures with isotope
dilution mass spectrometry. Estimated glomerular ltration
rate (eGFR) was calculated from calibrated creatinine, age,
and sex by using the CKD-EPI (Chronic Kidney Disease Epide-
miology Collaboration)
and the KDIGO (Kidney Disease
Improving Global Outcomes) stratication of eGFR
at the
baseline of the study in stable conditions, dened as no
changes in creatinine levels in the previous 6months. During
the follow-up, AKI was dened when a sudden drop in creat-
inine with posterior recovery at previous levels was recorded.
According to the RIFLE scale,
AKI severity was graded in
three categories: risk [1.5-fold increase in serum creatinine
(sCr)], injury (2.0-fold increase in sCr), and failure (3.0-fold in-
crease in sCr or sCr >4.0mg/dL). The number of episodes for
each patient has been quantied and graded.
Cardiovascular risk factor denition
Body mass index (BMI) was calculated by dividing measured
weight in kilograms by square of height in metres. Obesity
was dened as a BMI 30 kg/m
. Blood pressure was mea-
sured up to three times on the same day in a sitting position,
and hypertension was dened as an ofce mean systolic
blood pressure 140 mmHg, a mean diastolic blood pressure
90 mmHg, a recorded physician diagnosis, or medication
use. Diabetes was dened as a non-fasting glucose 200
mg/dL, a recorded physician diagnosis, medication use or an
HbA1c6.5%. Serum total cholesterol was measured enzy-
matically using the Cholesterol High Performance reagent
(Roche Diagnostics). High-density lipoprotein (HDL) choles-
terol was measured using a direct HDL reagent (Roche Diag-
nostics). Low-density lipoprotein cholesterol was calculated
by using the Friedewald formula. Dyslipidaemia was dened
2J.L. Holgado et al.
ESC Heart Failure (2020)
DOI: 10.1002/ehf2.12595
by total cholesterol >200 mg/dL and/or treatment with lipid-
lowering drugs.
Mortality and hospitalization follow-up
Participants were followed up for hospitalization for AHF
and for all-cause mortality until 31 December 2015. Causes
of hospitalization were recorded using codes of the Interna-
tional Classication of Diseases,
th Revision. Vital status
was determined by matching records and death certicates
from the Spanish National Death Index. Mortality included
all causes of death. Time to event was calculated for each
individual as the difference between the date of the
inclusion into the study and the date of the hospital admis-
sion, the date of death, or 31 December 2015, whichever oc-
curred rst.
Statistical analysis
The cumulative survival rates and HF events in each of the
groups (presence of CKD or AKI and the degree of AKI) were
analysed using KaplanMeier curves, and the log-rank test
was used to calculate the statistical signicance of the differ-
ences. The prognostic value of the eGFR groups or AKI was
assessed using a Cox regression hazard model to determine
the hazard ratio (HR) for risk of hospitalization and mortality.
Clinically relevant factors affecting the prognosis, including
age (continuous modelled as restricted cubic splines with 5
knots), sex (men or women), BMI (continuous), hypertension
(no or yes), diabetes (no or yes), angiotensin AT1receptor
blockers (ARBs), angiotensin-converting-enzyme inhibitors
(ACEi), anti-aldosterone drugs, and diuretics (Henle loop and
thiazides), were selected for inclusion in the multivariate
analysis. Multivariate Cox regression hazard model was per-
formed by using the backward stepwise selection.
General characteristics of the study population
A total of 30 529 patients with HF were included. Mean age
was 75 years, and 58% were female. Hypertension was pres-
ent in 89.4%, dyslipidaemia in 65.0%, and diabetes in 48.3%
of the participants. A total of 12 809 (42.0%) patients had
eGFR <60 mL/min/1.73 m
, among them 35.4% eGFR be-
tween 30 and 60 mL/min/1.73 m
and 6.5% between 15 and
30 mL/min/1.73 m
. The number of subjects with one episode
of AKI was 3161 (10.4%) and two or more in 809 (2.6%). The
main characteristics of the study population grouped by the
number of AKI episodes are shown in Table
. Patients with
AKI episodes were more frequently female with diabetes
and hypertension. Likewise, signicant lower eGFR values
were observed across the AKI severity groups. The treatments
are also shown in Table
. Patients with AKI were receiving
more diuretics, beta-blockers, and reninangiotensin aldoste-
rone system blockers (ARB, ACEi, and anti-aldosterone drugs).
Acute kidney injury episodes
During an average follow-up of 3.2years, 5294 episodes of
AKI in 3970 patients (13%), with incidence of 3.3/100
patients/year, were recorded. Only one episode was ob-
served in 3161 (10.4%), two in 537 (1.8%), and three or
more in 272 (0.9%). The odds ratio of a second episode after
the rst was 0.26 (95%CI0.240.28). According to the
severity, AKI risk was present in 2712 patients, injury in 821,
and failure in 437. The prevalence increases across the
reduction of GFR levels (Stages 1to 4:risk 7.6%, 6.8%,
11.3%, and 12.5%; injury 2.1%, 2.0%, 3.3%, and 5.5%; and
failure 0.9%, 0.6%. 1.4%, and 8.0%, respectively) and inci-
dence rate (Stages 1to 4:risk 2.0,1.8,3.2, and 3.7/100
patients/year; injury 0.5,0.5,0.9, and 1.6/100
patients/year; and failure 0.2,0.2,0.4, and 2.3/100
patients/year, respectively) (Figures
Acute kidney injury episodes and acute heart
failure hospitalization
A total of 3817 patients with AHF admission in the study pe-
riod were recorded, with incidence of 38.4/100 HF
patients/year. They were 3101 (81.2%) patients without AKI,
545 (14.3%) patients with one AKI episode, and 171 (4.5%)
patients with two or more episodes. According to the AKI se-
verity, AKI risk was present in 472 (12.4%), injury in 171
(4.5%), and failure in 73 (1.9%). The number of AKI episodes
[one HR 1.05 (0.981.13); two or more HR 2.01 (1.792.25)]
and severity [risk HR 1.05 (0.971.04); injury HR 1.41 (1.24
1.60); and failure HR 1.90 (1.642.20)] increases the risk of
hospitalization, when adjusted by age, sex, CKD stage, hyper-
tension, diabetes, ACEi/ARB, diuretics, number of visits to the
specialist, and number of admissions (Figure
Acute kidney injury episodes and mortality
During the study period, a total of 10 560 deaths were re-
corded, with incidence of 9.3/100 HF patients/year, with
8951 (33.7%, incidence of 9/100 patients/year) of subjects
without AKI episodes, 1180 (11.17%) of subjects with one ep-
isode, and 429 (4.06%) with two or more episodes. According
to the severity of AKI, risk episodes were present in 992
(36.6%), injury in 367 (44.7%), and failure in 250 (57.2%).
The number of episodes [one HR 1.05 (0.981.13); two or
AKI in acute heart failure 3
ESC Heart Failure (2020)
DOI: 10.1002/ehf2.12595
more HR 2.01 (1.792.25)] and severity [risk 1.05 (CI 0.97
1.14), injury 1.41 (CI 1.241.60), and failure 1.90 (CI 1.64
2.20)] increases mortality risk (Figure
). When the mortality
risk was assessed in each of the eGFR groups according to the
AKI severity, patients with eGFR of between 30 and 90
mL/min/1.73 m
are those in whom the risk was graded by
the severity of AKI episode. In patients with eGFR between
15 and 30 mL/min/1.73 m
, the risk of mortality is high in
all subjects, with and without AKI episodes.
In a large cohort of acute and chronic HF patients, AKI is a fre-
quent condition in ~15% of patients with at least one epi-
sode, with an increasing incidence according to the eGFR
group. AKI incidence and both number and severity of epi-
sodes increase the risk of hospital admission by AHF and all-
cause mortality.
The present study was conducted in a population from
the Valencian Community territory, with an EHR associated
with the public general-practice setting that has a 92%
coverage of the population living in the area. Every patient
has a unique personal identication number, which guaran-
tees the interoperability of the EHRs. Thus, administrative
data, including all prescriptions and dispensation of subsi-
dized treatments and hospitalization events, are linked to
the database that integrates all the health care interven-
tions and procedures that the patients received. Therefore,
this study includes information on baseline risk factors and
follow-up for mortality and hospitalizations from adults with
HF who had their serum creatinine repeatedly measured by
the public health system during the study period.
Dening and classifying the sudden decrease in renal func-
tion are still a matter of debate with several criteria used,
such as RIFLE,
and WRF.
One study com-
pared them in patients hospitalized due to acute heart de-
compensation to assess the benets of using one or two of
the AKI classication systems.
The authors concluded that
the potential advantages of the new classications, AKIN
and KDIGO, lie in the ability to identify those patients with
more severe degrees of AKI who will go on to experience ad-
verse events at 30 days and 1year. However, the differences
in terms of predictive abilities were only marginal.
and classication of AKI were performed based on the RIFLE
Table 1 General characteristics of the study population
All subjects No AKI AKI risk AKI injury AKI failure
Number 30 529 26 559 2712 821 437
Sex (M) 14 030 (46.0) 12 173 (45.8) 1232 (45.4)
379 (46.2)
246 (56.3)
Body mass index (kg/m
) 30.8 (5.8) 30.8 (5.8) 30.8 (5.6) 31.0 (5.7) 30.4 (6.5)
Age at diagnosis 75.1 (11.0) 75.1 (11.1) 75.4 (10.2) 75.9 (9.9) 74.6 (10.7)
eGFR (mL/min/1.73 m
) 65.0 (22.4) 66.0 (21.9) 59.8 (23.4)
58.2 (24.7)
46.5 (27.0)
CKD Stage 1, >90 13.4 13.8 11.4
CKD Stage 2, 9060 44.6 46.4 34.3 33.3 19.9
CKD Stage 3, 6030 35.4 34.2 45.1 42.9 35.5
CKD Stage 4, 3015 6.5 5.6 9.2 13.3 36.4
Average of visits
19.4 (19.1) 18.9 (18.2) 23.8 (23.1)
21.2 (24.6)
22.1 (26.1)
Acute HF hospitalization 3817 (12.5) 3101 (11.7) 472 (17.4)
171 (20.8)
73 (16.7)
Mortality 10 560 (34.6) 8951 (33.7) 992 (36.6) 367 (44.7)
250 (57.2)
Anaemia 16 145 (52.9) 13 534 (51.0) 1760 (64.9)
541 (65.9)
310 (70.9)
Diabetes 14 740 (48.3) 12 484 (47.0) 1536 (56.6)
475 (57.9)
245 (56.1)
Dyslipidaemia 19 831 (65.0) 17 135 (64.5) 1861 (68.6)
545 (66.4) 290 (66.4)
Hypertension 27 303 (89.4) 23 595 (88.8) 2526 (93.1)
767 (93.4)
415 (95.0)
Myocardial infarction 5569 (18.2) 4695 (17.7) 604 (22.3)
174 (21.2)
96 (22.0)
Atrial brillation 17 159 (56.2) 14 675 (55.3) 1689 (62.3)
541 (65.9)
254 (58.1)
Diuretics 22 715 (74.4) 19 471 (73.3) 2232 (82.3)
663 (80.8)
349 (79.9)
Beta-blockers 13 131 (43.0) 11 199 (42.2) 1326 (48.9)
406 (49.5)
200 (45.8)
ACEi/ARB 19 859 (65.0) 17 053 (64.2) 1924 (70.9)
596 (72.6)
286 (65.4)
Calcium antagonists 7795 (25.5) 6569 (24.7) 797 (29.4)
258 (31.4)
171 (39.1)
NSAIDs 8660 (28.4) 7668 (28.9) 711 (26.2)
191 (23.3)
90 (20.6)
Anti-aldosterone 5477 (17.9) 4537 (17.1) 631 (23.3)
216 (26.3)
93 (21.3)
ACEi, angiotensin-converting-enzyme inhibitor; AKI, acute kidney injury; ARB, angiotensin receptor blocker; CKD, chronic kidney disease;
eGFR, estimated glomerular ltration rate; NSAIDs, non-steroidal anti-inammatory drug.
Values are number (percentage).
Difference with no AKI group.
Difference with AKI risk group.
Difference with AKI injury group.
Visits to specialists and primary care physicians.
4J.L. Holgado et al.
ESC Heart Failure (2020)
DOI: 10.1002/ehf2.12595
scale on the changes in serum creatinine, without the criteria
that include urine output, owing to the characteristics of the
database that do not record specic data from the hospitali-
zation period or the ambulant control.
In patients with HF, AKI is a frequent event in which the
haemodynamic status, low cardiac output or congestive
status, and the impact of drugs, mainly diuretics and renin
angiotensin system blockade, are relevant factors. As it is ex-
pected, the incidence increases in patients with eGFR <60
mL/min/1.73 m
owing to the lower renal functional reserve
produced by the HF itself or owing to age and co-morbidities
that increase the risk of renal functional deterioration. The
Figure 1Risk to develop AKI episodes by CKD stage. Using as a reference the group in CKD Stage 1, the risk of risk (A) was HR 0.87 (95%CI0.760.99)
in Stage 2,HR1.48 (95%CI1.291.69) in Stage 3, and HR 1.95 (95%CI1.652.30) in Stage 4.Injury (B) was HR 0.97 (95%CI0.761.25) in Stage 2,HR
1.58 (95%CI1.222.05) in Stage 3, and HR 3.49 (95%CI2.614.66) in Stage 4.Failure (C) was HR 1.09 (95%CI0.721.63) in Stage 2,HR2.75 (95%CI
1.844.11) in Stage 3, and HR 16.36 (95%CI10.8424.69) in Stage 3. Lines: blue (Stage 1), orange (Stage 2), green (Stage 3), and red (Stage 4). AKI,
acute kidney injury; CI, condence interval; CKD, chronic kidney disease; HR, hazard ratio.
Figure 2Percentage of patients with AKI severity episodes by CKD stage. AKI, acute kidney injury; CKD, chronic kidney disease.
AKI in acute heart failure 5
ESC Heart Failure (2020)
DOI: 10.1002/ehf2.12595
more reduced eGFR increases not only the incidence but also
the severity and reduces the lag period of time free of AKI.
These data are in agreement with those of previous studies
performed in AHF subjects, but no information was available
on the total HF population. Whether or not the incidence was
higher in patients with HF with reduced ejection fraction than
in those with HF with preserved ejection fraction, it is not
possible to assess it in the present study because the left ven-
tricular function was not properly recorded in a great propor-
tion of patients.
The importance of co-morbidities in the evolution and
prognosis of HF has been emphasized,
and several studies
have tried to identify factors related with hospitalization
and prognosis.
Besides ischaemic heart disease, other
factors such as non-compliance to the prescribed treatments
or diet, infections, arrhythmias, uncontrolled hypertension,
anaemia, and renal dysfunction are among the most common
reasons for AHF, progression, and mortality. The relevance
and impact of AKI in terms of prognostic value for hospital ad-
mission by AHF or mortality have been investigated in the
present study. Hospital admissions were considered only for
those due to AHF avoiding total hospitalizations because pa-
tients with HF could have admission due to decompensation
or other deadly co-morbidities. AKI increases risk of hospital-
ization and mortality, indicating the more fragile status of the
The limitations and strengths of the present study should
be considered. First is with regards the denition of AKI.
While we recognized the utility of AKI denition in epidemi-
ology and clinical research arenas, it is not sufciently vali-
dated for use in the diagnosis and clinical management of
patients. The study does not identify the cause of mortality,
whether it is cardiovascular or not, although the AKI repre-
sents a status of fragility that can alert about the very high
risk of all-cause mortality. Moreover, the lack of assessment
of natriuretic peptides and left ventricular ejection fraction
precluded to better dissect the effect of AKI across the dif-
ferent phenotypes of HF. The large sample size and the av-
erage follow-up are useful to properly assess the
signicance of changes in renal function in terms of
In conclusion, the study described the prognostic value of
sudden renal function decline beyond the episode of AKI
and pointed to the patients with more future risk who re-
quire review of treatment and more careful follow-up. As
the problem of hospitalization for AHF is expected to
Figure 3Risk of AHF hospital admissions by AKI number (A), one-episode HR 1.19 (1.091.31), two or more episodes HR 1.84 (1.572.15). Line colours:
blue (no AKI), orange (one AKI), and red (two or more AKI). Severity (B) of AKI episodes risk 1.17 (1.061.3), injury 1.80 (1.542.1), and failure 1.38
(1.091.75). Line colours as in Figure
. AHF, acute heart failure; AKI, acute kidney injury; HR, hazard ratio.
6J.L. Holgado et al.
ESC Heart Failure (2020)
DOI: 10.1002/ehf2.12595
increase, we have to design strategies of management in the
future. Further research is needed to nd which is the best
plan or site of management for these patients, taking into ac-
count that this can vary according to the population or the or-
ganization of health systems.
We acknowledge the contribution of the Health Authorities
of the Conselleria de Salud UniversalGeneralitat Valenciana
for allowing to use their data.
Conicts of Interest
None declared.
This work was supported by the BigData@Heart (IMI2-
FPP116074-2), BigMedilytics (ICT-15-780495), and CIBERObn
Carlos III Health Institute (PI16/01402).
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... Heart failure as an independent risk for mortality in HD patients, whether incident or chronic, has been studied and confirmed. (32)(33)(34)(35)(36) Among HD patients, those who have cardiovascular disease have worse prognosis. Cardiovascular disease is the most common cause of death in HD patients. ...
... Several studies have also shown that patients with heart failure that develop acute or acute-on-chronic kidney disease with HD dependence have a poorer prognosis, with a median survival of less than 4 months. (36)(37) AKI requiring dialysis is associated with substantial morbidity, mortality, and progression to CKD. Patients are considered to have reached ESRD after 90 days of AKI with dialysis requirement. ...
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Introduction: Chronic kidney disease has significant morbidity and mortality worldwide. Various studies have demonstrated that incident patients experience a higher mortality rate within the first 3 months of dialysis. Methods: A single-center retrospective case-control study (1:3) was performed to determine early (
... The incidence of AKI in population is ~20%. [40][41][42] The significance of WRF among patients with AHF has been emphasized for years. 40,43 The presence of WRF, understood as an increase in SCr > 0.3 mg/dL in serum or a decrease in eGFR by >25% (expressed in mL/min/1.73 ...
... [40][41][42] The significance of WRF among patients with AHF has been emphasized for years. 40,43 The presence of WRF, understood as an increase in SCr > 0.3 mg/dL in serum or a decrease in eGFR by >25% (expressed in mL/min/1.73 m 2 , calculated according to the Modification of Diet in Renal Disease (MDRD) formula), together with worsening or lack of improvement in signs and symptoms of AHF, is known as the "true WRF". ...
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Heart failure (HF) is a pathophysiologically complex disease that is exceptionally heterogeneous in terms of its etiology. It is associated with unsatisfactorily high mortality, both in-hospital and post-discharge, as well as with very frequent rehospitalizations. High phenotypic variability, coexistence of various hemodynamic disorders (such as changes in systemic and pulmonary vascular resistance, increased central venous pressure, impaired heart cardiac output, and fluid overload) and coexisting metabolic and neurohormonal disorders may eventually lead to impaired systemic perfusion. Congestion that impairs renal perfusion has a significant impact on both glomerular filtration and the renal tubular function. This review article discusses the importance of changes caused by HF in various nephron segments, phenotyping of cardiorenal syndromes, the role of effective natriuresis in decongestion, and the importance of known and new diagnostic biomarkers in predicting renal dysfunction. A better understanding of cardiac and renal interactions may help in selecting an effective, efficient and nephroprotective strategy of treatment for patients with HF.
... The WRF and AKI in AHF are common complications associated with ominous outcomes [4]. The occurrence of AKI has been estimated at 9-13% of AHF patients [16,17]. The underlying causes of the WRF in AHF are complex and not fully understood; the most prominent hypotheses include the impact of, i.a., congestion [18]. ...
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Acute heart failure (AHF) is a common and severe condition with a poor prognosis. Its course is often complicated by worsening renal function (WRF), exacerbating the outcome. The population of AHF patients experiencing WRF is heterogenous, and some novel possibilities for its analysis have recently emerged. Clustering is a machine learning (ML) technique that divides the population into distinct subgroups based on the similarity of cases (patients). Given that, we decided to use clustering to find subgroups inside the AHF population that differ in terms of WRF occurrence. We evaluated data from the three hundred and twelve AHF patients hospitalized in our institution who had creatinine assessed four times during hospitalization. Eighty-six variables evaluated at admission were included in the analysis. The k-medoids algorithm was used for clustering, and the quality of the procedure was judged by the Davies–Bouldin index. Three clinically and prognostically different clusters were distinguished. The groups had significantly (p = 0.004) different incidences of WRF. Inside the AHF population, we successfully discovered that three groups varied in renal prognosis. Our results provide novel insight into the AHF and WRF interplay and can be valuable for future trial construction and more tailored treatment.
... On the other hand, bolus-free levosimendan administration may have prevented significant hypotension reported in patients after administration of a bolus of the inodilatator levosimendan (19). These findings fit well into data reported here, showing stable kidney function after levosimendan in the context of acute heart failure, a condition known to affect kidney function normally negatively (37). ...
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Background Patients with heart failure frequently present with kidney dysfunction. Kidney function is relevant, as prognosis declines with reduced kidney function and potentially beneficial drugs like levosimendan are contraindicated for missing safety data. Materials and methods A single-center retrospective registry study was conducted including all patients receiving levosimendan on a medical intensive care unit between January 2010 and December 2019. Exclusion criteria were a follow-up less than 24 h or missing glomerular filtration rate (eGFR) before administration of levosimendan. The first course of treatment was evaluated. Patients were stratified by eGFR before drug administration and the primary endpoint was a composite of supraventricular-, ventricular tachycardia and death within 7 days after administration of levosimendan. An internal control group was created by propensity score matching. Results A total of 794 patients receiving levosimendan were screened and 368 unique patients were included. Patients were predominantly male (73.6%) and median age was 63 years. Patients were divided by eGFR into three groups: >60 ml/min/1.73 m ² ( n = 110), 60–30 ml/min/1.73 m ² ( n = 130), and <30 ml/min/1.73 m ² ( n = 128). ICU survival was significantly lower in patients with lower eGFR (69.1, 57.7, and 50.8%, respectively, p = 0.016) and patients with lower eGFR were significantly older and had significantly more comorbidities. The primary combined endpoint was reached in 61.8, 63.1, and 69.5% of subjects, respectively ( p = 0.396). A multivariate logistic regression model suggested only age ( p < 0.020), extracorporeal membrane oxygenation ( p < 0.001) or renal replacement therapy ( p = 0.028) during day 1–7 independently predict the primary endpoint while kidney function did not ( p = 0.835). A propensity score matching of patients with eGFR < 30 and >30 ml/min/1.73 m ² based on these predictors of outcome confirmed the primary endpoint ( p = 0.886). Conclusion The combined endpoint of supraventricular-, ventricular tachycardia and death within 7 days was reached at a similar rate in patients independently of kidney function. Prospective randomized trials are warranted to clarify if levosimendan can be used safely in severely reduced kidney function.
... CHF leads to complex interactions between the heart and the kidneys (39). Patients with a history of CHF are usually at increased risk of AKI due to inadequate renal reserve function and reduced renal perfusion (40). Moreover, our study shows that patients with AIS who develop AKI are usually associated with a higher HR. ...
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Background This study sought to develop and validate a dynamic nomogram chart to assess the risk of acute kidney injury (AKI) in patients with acute ischemic stroke (AIS). Methods These data were drawn from the Medical Information Mart for Intensive Care III (MIMIC-III) database, which collects 47 clinical indicators of patients after admission to the hospital. The primary outcome indicator was the occurrence of AKI within 48 h of intensive care unit (ICU) admission. Independent risk factors for AKI were screened from the training set using univariate and multifactorial logistic regression analyses. Multiple logistic regression models were developed, and nomograms were plotted and validated in an internal validation set. Based on the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) to estimate the performance of this nomogram. Results Nomogram indicators include blood urea nitrogen (BUN), creatinine, red blood cell distribution width (RDW), heart rate (HR), Oxford Acute Severity of Illness Score (OASIS), the history of congestive heart failure (CHF), the use of vancomycin, contrast agent, and mannitol. The predictive model displayed well discrimination with the area under the ROC curve values of 0.8529 and 0.8598 for the training set and the validator, respectively. Calibration curves revealed favorable concordance between the actual and predicted incidence of AKI ( p > 0.05). DCA indicates the excellent net clinical benefit of nomogram in predicting AKI. Conclusion In summary, we explored the incidence of AKI in patients with AIS during ICU stay and developed a predictive model to help clinical decision-making.
... Renal assessment and KDIGO categories. Serum creatinine was measured and estimated glomerular filtration rate (eGFR) was calculated from creatinine, age and sex using the CKD-EPI 22 . Albuminuria and/or proteinuria was assessed in first voiding urine in the morning and expressed as the ratio with urinary creatinine (mg/g). ...
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The objective is to assess the impact of anticoagulant treatment in non-valvular atrial fibrillation (AF) and different categories of renal dysfunction in real world. Electronic Health recordings of patients with diagnosis of AF and renal function collected throughout 5 years and classified according to KDIGO categories. Stroke, transitory ischemic attack (TIA), intracranial hemorrhage and all-cause mortality were identified. Anticoagulant treatments during the study period were classified in untreated (never received therapy), VKA, NOAC and Aspirin. The risk of events was calculated by Cox-proportional hazard models adjusted by confounders. A total of 65,734 patients with AF, mean age 73.3 ± 10.49 years old and 47% females and follow-up of 3.2 years were included. KDIGO classification were: G1 33,903 (51.6%), G2 17,456 (26.6%), G3 8024 (12.2%) and G4 6351 (9.7%). There were 8592 cases of stroke and TIA, 437 intracranial hemorrhage, and 9603 all-cause deaths (incidence 36, 2 and 38 per 10 ³ person/year, respectively). 4.1% of patients with CHA2DS2-VASc Score 2 or higher did not receive anticoagulant therapy. Risk of stroke, TIA, and all-cause mortality increased from G1 to G4 groups. Anticoagulant treatments reduced the risk of events in the four categories, but NOAC seemed to offer significantly better protection. Renal dysfunction increases the risk of events in AF and anticoagulant treatments reduced the risk of stroke and all-cause mortality, although NOAC were better than VKA. Efforts should be done to reduce the variability in the use of anticoagulants even in this high risk group.
... Due to the special interaction in heart, liver and kidney, heart failure patients are often accompanied with liver and kidney damage, which always indicates worse clinical prognosis (31)(32)(33). In our study, FGF21 was positively correlated with Cr (r = 0.33, p < 0.001) and BUN (r = 0.31, p < 0.001), which means that there are close relationship between FGF21 and renal function in AHF patients. ...
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Background Recent studies of fibroblast growth factor 21 (FGF21), first recognized as a regulator of glucose and lipid metabolism, have found that the level of in serum FGF21 is associated with the prognosis of many cardiovascular diseases, but its relationship to acute heart failure (AHF) patients remains unknown. Our study aimed to investigate whether circulating FGF21 could predict the short-term prognosis of AHF patients.Methods Four hundred and two AHF patients and 19 healthy controls were recruited into the prospective cohort study, and blood samples of participants were collected, in tubes without anticoagulant, within the first 24 h after hospital admission. Serum FGF21 levels were detected by enzyme-linked immunosorbent assay (ELISA). All patients were followed-up at least 6 months after discharge. The primary endpoint was all-cause death, and secondary endpoint was a composite endpoint of death and heart failure readmission. Mortality and composite end point events were analyzed using Kaplan-Meier curves. ROC curves compared the difference between the FGF21 and NT-proBNP in predicting 3- and 6-months mortality. Time-to-event data were evaluated using Kaplan-Meier estimation and Cox proportional hazards models.ResultsIn the present study, the serum FGF21 concentrations were significantly higher in the 402 AHF patients enrolled, compared with the 19 healthy controls (p < 0.001). The average age was 70 (±12) years, and 58% were males. Participants were divided into two groups according to the median FGF21 level (262 pg/ml): a high FGF21 group (n = 201, FGF21 ≥ 262 pg/ml) and low FGF21 group (n = 201, FGF21 <262 pg/ml). FGF21 was positively correlated with NT-proBNP, BUN, AST, creatinine and cholesterol, and negatively correlated with ALB and HDL. After a median follow-up of 193 days, the high FGF21 group had higher mortality and composite endpoint events compared with the low FGF21 group (HR: 3.91, 95% CI 2.21–6.92, p <0.001), even after adjusting for NT-proBNP (HR: 3.17, 95% CI 1.72–5.81, p < 0.001). ROC analysis shows that FGF21 was better than NT-proBNP in predicting death at both 3 (AUC, 0.77 vs. 0.63, p < 0.001) and 6 months (AUC, 0.78 vs. 0.66).Conclusion High baseline FGF21 levels are associated with adverse clinical outcomes in AHF patients. Serum FGF21 might be a potential predictive biomarker of AHF patients.
... In the PROTECT Trial which included patients with some degree of CKD, many patients had a creatinine increase during hospitalization, and those experiencing more severe CKD showed a higher mortality during the 60 days followup (32). More recently, Holgado et al. demonstrated that AHF patients with more severe AKI degree had poorer prognosis (33). Interestingly, when WRF is associated with hemoconcentration or reduction in NTproBNP, it is not connected to an increased adverse event rate (34). ...
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Background The role of worsening renal function during acute heart failure (AHF) hospitalization is still debated. Very few studies have extensively evaluated the renal function (RF) trend during hospitalization by repetitive measurements.Objectives To investigate the prognostic relevance of different RF trajectories together with the congestion status in hospitalized patients.Methods This is a post hoc analysis of a multi-center study including 467 patients admitted with AHF who were screened for the Diur-AHF Trial. We recognized five main RF trajectories based on serum creatinine and estimated glomerular filtration rate (eGFR) behavior. According to the RF trajectories our sample was divided into 1-stable (S), 2-transient improvement (TI), 3-permanent improvement (PI), 4-transient worsening (TW), and 5-persistent worsening (PW). The primary outcome was the combined endpoint of 180 days including all causes of mortality and re-hospitalization.ResultsWe recruited 467 subjects with a mean congestion score of 3.5±1.08 and a median creatinine value of 1.28 (1.00–1.70) mg/dl, eGFR 50 (37–65) ml/min/m2 and NTpro B-type natriuretic peptide (BNP) 7,000 (4,200–11,700) pg/ml. A univariate analysis of the RF pattern demonstrated that TI and PW patterns were significantly related to poor prognosis [HR: 2.71 (1.81–4.05); p < 0.001; HR: 1.68 (1.15–2.45); p = 0.007, respectively]. Conversely, the TW pattern showed a significantly protective effect on outcome [HR:0.34 (0.19–0.60); p < 0.001]. Persistence of congestion and BNP reduction ≥ 30% were significantly related to clinical outcome at univariate analysis [HR: 2.41 (1.81–3.21); p < 0.001 and HR:0.47 (0.35–0.67); p < 0.001]. A multivariable analysis confirmed the independently prognostic role of TI, PW patterns, persistence of congestion, and reduced BNP decrease at discharge.Conclusions Various RF patterns during AHF hospitalization are associated with different risk(s). PW and TI appear to be the two trajectories related to worse outcome. Current findings confirm the importance of RF evaluation during and after hospitalization.
Objectives: Old age was identified as a strong risk factor for acute kidney injury (AKI). Our objectives were to provide estimates of AKI, risk factors and outcomes in patients ≥ 75 years for whom data are scarce. Methods: Observational studies and randomized controlled trials between 2005 and 2021 with patients of mean or median age ≥ 75 years, reporting AKI according to current definitions. Data on AKI incidence, risk factors and mortality were analyzed separately in unselected (UC) and acute heart failure (AHF) cohorts. Results: Twenty-six observational studies and 4 randomized controlled trials with 51,111 UC and 25,414 AHF patients were included. Ages averaged 79.4 and 79.8 years, respectively. Pooled risk ratios (RRs) of AKI rates were 26.29% (95% confidence intervals (CI) 13.20-41.97) (UC) and 24.21% (95% CI 20.03-28.65) (AHF). In both cohorts, AKI was associated with decreased estimated glomerular filtration rate at baseline, chronic kidney disease (UC: RR 1.80 (95% CI 1.15-2.80), AHF: RR 1.51 (95% CI 1.26-1.95) and hypertension (UC: RR 1.30 (95% CI 1.09-1.56), AHF: RR 1.07 (95% CI 1.05-1.09). RRs of AKI in patients on renin-angiotensin-inhibitors were 0.87 (95% CI 0.78-0.97) and 0.88 (95% CI 0.78-0.98) in UC and AHF, respectively. AKI was consistently associated with increased risk of in-hospital mortality (UC: RR 3.15 (95% CI 2.28-4.35), AHF: RR 4.28 (95% CI 2.53-7.24). Conclusion: AKI is frequent in patients ≥ 75 years. While reduced renal function at baseline, CKD and hypertension were associated with AKI development, renin-angiotensin-inhibitors may be protective. Older AKI patients showed higher short-term mortality rates.
Background: Studies have shown that more than half of patients with heart failure (HF) with acute kidney injury (AKI) have newonset AKI, and renal function evaluation markers such as estimated glomerular filtration rate are usually not repeatedly tested during the hospitalization. As an independent risk factor, delayed AKI recognition has been shown to be associated with the adverse events of patients with HF, such as chronic kidney disease and death. Objective: The aim of this study is to develop and assess of an unsupervised machine learning model that identifies patients with HF and normal renal function but who are susceptible to de novo AKI. Methods: We analyzed an electronic health record data set that included 5075 patients admitted for HF with normal renal function, from which 2 phenogroups were categorized using an unsupervised machine learning algorithm called K-means clustering. We then determined whether the inferred phenogroup index had the potential to be an essential risk indicator by conducting survival analysis, AKI prediction, and the hazard ratio test. Results: The AKI incidence rate in the generated phenogroup 2 was significantly higher than that in phenogroup 1 (group 1: 106/2823, 3.75%; group 2: 259/2252, 11.50%; P<.001). The survival rate of phenogroup 2 was consistently lower than that of phenogroup 1 (P<.005). According to logistic regression, the univariate model using the phenogroup index achieved promising performance in AKI prediction (sensitivity 0.710). The generated phenogroup index was also significant in serving as a risk indicator for AKI (hazard ratio 3.20, 95% CI 2.55-4.01). Consistent results were yielded by applying the proposed model on an external validation data set extracted from Medical Information Mart for Intensive Care (MIMIC) III pertaining to 1006 patients with HF and normal renal function. Conclusions: According to a machine learning analysis on electronic health record data, patients with HF who had normal renal function were clustered into separate phenogroups associated with different risk levels of de novo AKI. Our investigation suggests that using machine learning can facilitate patient phengrouping and stratification in clinical settings where the identification of high-risk patients has been challenging.
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Abstract Acute kidney injury (AKI) is a frequent complication of hospitalization and is associated with an increased risk of chronic kidney disease (CKD), end-stage renal disease (ESRD), and mortality. While AKI is a known risk factor for short-term adverse outcomes, more recent data suggest that the risk of mortality and renal dysfunction extends far beyond hospital discharge. However, determining whether this risk applies to all patients who experience an episode of AKI is difficult. The magnitude of this risk seems highly dependent on the presence of comorbid conditions, including cardiovascular disease, hypertension, diabetes mellitus, preexisting CKD, and renal recovery. Furthermore, these comorbidities themselves lead to structural renal damage due to multiple pathophysiological changes, including glomeruloscleroses and tubulointerstitial fibrosis, which can lead to the loss of residual capacity, glomerular hyperfiltration, and continued deterioration of renal function. AKI seems to accelerate this deterioration and increase the risk of death, CDK, and ESRD in most vulnerable patients. Therefore, we strongly advocate adequate hemodynamic monitoring and follow-up in patients susceptible to renal dysfunction. Additionally, other potential renal stressors, including nephrotoxic medications and iodine-containing contrast fluids, should be avoided. Unfortunately, therapeutic interventions are not yet available. Additional research is warranted and should focus on the prevention of AKI, identification of therapeutic targets, and provision of adequate follow-up to those who survive an episode of AKI.
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Purpose of review: Acute decompensated heart failure (ADHF) is one of the biggest challenges in the management of chronic heart failure. Despite several advances in medical and device therapy, high readmission and mortality rates continue to be a burden on healthcare systems worldwide. The aim of the current review is to provide an overview on current as well as future approaches in cardiorenal interactions in patients with ADHF. Recent findings: One of the strongest predictors of adverse outcomes in ADHF is renal dysfunction, referred to as cardiorenal syndromes (CRS) or cardiorenal interactions. Patients with ADHF frequently develop worsening of renal function (WRF) and/or acute kidney injury (AKI). Recent studies brought new information about biomarkers in diagnosing and predicting prognosis of CRS. Among others, dry weight at hospital discharge is considered a surrogate marker of successful treatment in ADHF patients with/without renal dysfunction. The etiology of WRF appears to be an important factor for determining risk related to WRF as well as clinical management. The hypertonic saline used as adjunctive therapy for intravenous loop diuretics and/or induction of aquaresis (e.g., using tolvaptan) may be promising and efficient approaches in the future.
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Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a signi cant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate de nition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the de nition, epidemiology and pathophysiology of AKI.
Background and objectives: AKI in the hospital is common and is associated with excess mortality. We examined whether AKI is also independently associated with a higher risk of different cardiovascular events in the first year after discharge. Design, setting, participants, & measurements: We conducted a retrospective analysis of a cohort between 2006 and 2013 with follow-up through 2014, within Kaiser Permanente Northern California. We identified all adults admitted to 21 hospitals who had one or more in-hospital serum creatinine test result and survived to discharge. Occurrence of AKI was on the basis of Kidney Disease: Improving Global Outcomes diagnostic criteria. Potential confounders were identified from comprehensive inpatient and outpatient, laboratory, and pharmacy electronic medical records. During the 365 days after discharge, we ascertained occurrence of heart failure, acute coronary syndromes, peripheral artery disease, and ischemic stroke events from electronic medical records. Results: Among a matched cohort of 146,941 hospitalized adults, 31,245 experienced AKI. At 365 days postdischarge, AKI was independently associated with higher rates of the composite outcome of hospitalization for heart failure and atherosclerotic events (adjusted hazard ratio [aHR], 1.18; 95% confidence interval [95% CI], 1.13 to 1.25) even after adjustment for demographics, comorbidities, preadmission eGFR and proteinuria, heart failure and sepsis complicating the hospitalization, intensive care unit (ICU) admission, length of stay, and predicted in-hospital mortality. This was driven by an excess risk of subsequent heart failure (aHR, 1.44; 95% CI, 1.33 to 1.56), whereas there was no significant association with follow-up atherosclerotic events (aHR, 1.05; 95% CI, 0.98 to 1.12). Conclusions: AKI is independently associated with a higher risk of cardiovascular events, especially heart failure, after hospital discharge.
Background In-hospital worsening heart failure (WHF) occurs frequently in patients hospitalized for acute heart failure (AHF) and has strongly negative prognostic associations. It may be a useful endpoint in studies of AHF management but important questions remain regarding optimization of its definition and variability in its incidence. Methods Our objective was to survey the full extent of clinical interest in WHF and assess the impact of baseline variables and trial design on outcomes. PubMed, Embase, and BIOSIS were searched systematically for clinical studies that had in-hospital WHF as an endpoint. Differences in definitions of in-hospital WHF were reviewed for their potential impact on observed incidence of WHF and its associations with post-discharge outcomes. Results The search identified 35 publications representing 13 interventional trials, 3 observational studies, several different classes of therapeutic agent, and 78,752 patients overall. Incidence of in-hospital WHF varied greatly—from 4.2% to 37%. Concerning the impact of differences in the way in which WHF was defined, two important factors were physician determination of worsening and whether intensification of diuretic therapy alone was defined as a WHF event. Patients having in-hospital WHF were at substantially greater risk for death and longer length of stay during index hospitalizations, all-cause and heart-failure rehospitalization, cardiovascular complications, renal failure, all-cause death, cardiovascular death, and higher healthcare costs post-discharge. Conclusions There is diverse interest in selecting in-hospital WHF as an endpoint in clinical trials. Differences in reported incidence are complexly related to differences in the way in which WHF is defined.
Aims: To analyse the characteristics of hospitalized patients for AHF, with special attention to the clustering of morbidities. Methods and results: Clinical records of patients, admitted in Internal Medicine due to AHF, during three years, were reviewed. The characteristics of patients-episodes were registered and key indicators of performance. Multiple correspondence analysis (MCA) was used to assess the distribution of morbidities. LR models were used to study clinical variables related with death or readmission. The median age was 80y, predominantly women and with multiple morbidities. As it was expected, CVRF were the main associated comorbidities followed by respiratory diseases, CKD and chronic anaemia. In the MCA, all the CVRF clustered around the origin so they explained little of the total inertia. Male sex, young age, IHD, obesity and lung disease were more common in reduced EF whereas female, older age and thyroid disease were more common in preserved EF. The confidence ellipses for death in hospitalization or during the follow-up or for readmissions overlapped, so it was not possible to identify clusters of morbidities to predict outcomes. The main causes for AHF were infections, anaemia and RVR in AF. Nearly 16% died during the hospitalization whereas 25.6% died and 56.3% were re-hospitalized during the following year after the discharge. Previous or repeated admissions to the hospital were the best single predictors for death or readmission. Conclusions: Strategies to control infections, anaemia and AF, in the outpatient settings, might help to reduce the burden of AHF, although this remains to be proven.
Aim: To provide a robust estimates of mortality risk in acute coronary syndrome (ACS) associated acute kidney injury (AKI) to inform clinical practice and policy. Methods: A meta-analysis of cohort studies evaluating outcomes of ACS and which reported AKI and AKI associated mortality. Studies were excluded if they incorporated patients not admitted through the emergency department (i.e. for elective procedures), were limited to cardiogenic shock or cardiac arrest, or relied on registry data for outcomes without further adjudication. The predictor was ACS associated AKI and outcomes early (30-day or in-hospital) mortality and late-mortality (post-hospital discharge). Results: Thirty-six studies with 37 unique cohorts comprising 100,476 patients were included. The pooled rate of ACS-associated AKI was 15.8%. In 32 cohorts reporting early mortality the crude early mortality rate was 15.0% amongst those with AKI compared with 2.0% amongst those without AKI. The pooled estimate of the relative risk of AKI-associated early mortality was 4.1 (95% Confidence Interval: 3.3 to 5.0) with high heterogeneity between studies (I(2) = 84% [61% to 88%]). When heterogeneity was accounted for mathematically using credibility ceilings, the risk of mortality was lower, but still clinically significant (3.1 (2.6 to 3.6)). In 19 cohorts reporting late mortality (1 to 10 years), the relative risk of AKI-associated mortality was 2.6 (2.0 to 3.3) with moderate heterogeneity (I(2) = 65% [35% to 88%]). Following application of credibility ceiling relative risk estimate dropped to 2.2 (1.9 to 2.6). Conclusions: ACS-associated AKI is associated with more than a three-fold increase in early mortality and more than two-fold in long-term mortality. This article is protected by copyright. All rights reserved.
Heart failure (HF) is a major health-care problem and the prognosis of affected patients is poor. HF often coexists with a number of comorbidities of which declining renal function is of particular importance. A loss of glomerular filtration rate, as in acute kidney injury (AKI) or chronic kidney disease (CKD), independently predicts mortality and accelerates the overall progression of cardiovascular disease and HF. Importantly, cardiac and renal diseases interact in a complex bidirectional and interdependent manner in both acute and chronic settings. From a pathophysiological perspective, cardiac and renal diseases share a number of common pathways, including inflammatory and direct, cellular immune-mediated mechanisms; stress-mediated and (neuro)hormonal responses; metabolic and nutritional changes including bone and mineral disorder, altered haemodynamic and acid-base or fluid status; and the development of anaemia. In an effort to better understand the important crosstalk between the two organs, classifications such as the cardio-renal syndromes were developed. This classification might lead to a more precise understanding of the complex interdependent pathophysiology of cardiac and renal diseases. In light of exceptionally high mortality associated with coexisting HF and kidney disease, this Review describes important crosstalk between the heart and kidney, with a focus on HF and kidney disease in the acute and chronic settings. Underlying molecular and cellular pathomechanisms in HF, AKI and CKD are discussed in addition to current and future therapeutic approaches.
Acute heart failure (AHF) is a complex syndrome characterized by worsening heart failure (HF) symptoms that requires escalation of therapy. Intrinsic cardiac abnormalities and comorbid conditions, including lung and renal disease, and sleep-disordered breathing, can contribute to the development of AHF. In this Review, we summarize and discuss the literature on the clinical evaluation and underlying pathophysiology of AHF. Important features of AHF evaluation include identification of precipitating factors to the disease, and assessment of circulatory-renal limitations associated with use of HF medications, prior HF hospitalizations, congestion and perfusion profiles, and end-organ dysfunction. The pathophysiological contributions of endothelial dysfunction, neurohormonal activation, venous congestion, and myocardial injury to the development of AHF are also discussed. These potential causative mechanisms provide a framework for clinicians to evaluate and manage patients with AHF and highlight possible future targets for therapies designed to improve clinical outcomes.