Une promenade dans l'épidémiologie de l'insuffisance ... · PDF...
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Une promenade dans
l'épidémiologie de l'insuffisance
rénale aiguë en quatre étapes
Fernando Liaño
Hospital Universitario Ramón y Cajal Madrid, España
Genéve, 14-12-2012
Préambule
Histoire
L'épidémiologie dans l'unité de soins
intensifs
Un appel de réveil
Une promenade dans
l'épidémiologie de l'insuffisance
rénale aiguë en quatre étapes:
Préambule
Histoire
L'épidémiologie dans l'unité de soins
intensifs
Un appel de réveil
Une promenade dans
l'épidémiologie de l'insuffisance
rénale aiguë en quatre étapes:
AKI epidemiology runs fast
Hsu RK et al. In 2012 stated:
“Our findings are consistent
with and extend on older studiesshowing an increase in disease (AKI)
incidence in the United States
over time7,8”
Hsu RK et al. J Am Soc Nephrol 2013. doi: 10.1681/ASN.2012080800
7.-Hsu CY et al.Kidney Int 2007
8.- Waikar SS et al. J Am Soc Nephrol 2006
AKI epidemiology runs fast
Hsu RK et al. In 2012 stated:
“Our findings are consistent
with and extend on older studiesshowing an increase in disease (AKI)
incidence in the United States
over time7,8”
Hsu RK et al. J Am Soc Nephrol 2013. doi: 10.1681/ASN.2012080800
7.-Hsu CY et al.Kidney Int 2007
8.- Waikar SS et al. J Am Soc Nephrol 2006
Préambule
Histoire
L'épidémiologie dans l'unité de soins
intensifs
Un appel de réveil
Une promenade dans
l'épidémiologie de l'insuffisance
rénale aiguë en quatre étapes:
Clinical & epidemiological
cornerstones in ARF/AKI
Crush
syndrome (Bywaters)
Definition &
standardization
RIFLE (Bellomo)
1917
1941
19771973
1985
2004
War
nephritis (Weldon)
1st Acute
dialysis(Kolf)
Isolated
UF
(Bergström)
1st CAVHF (Kramer)
Biomarkers
(Mishra)
2005
1951
2007
Long-term
outcomes (Schiffel/liaño)
RRT
Dosification (Ronco, Schiffl)
APACHE II (Knaus)
1990's1990
2000
Clinical & epidemiological
cornerstones in ARF/AKI
Crush
syndrome (Bywaters)
Definition &
standardization
RIFLE (Bellomo)
1917
1941
19771973
1985
2004
War
nephritis (Weldon)
1st Acute
dialysis(Kolf)
Isolated
UF
(Bergström)
1st CAVHF (Kramer)
Biomarkers
(Mishra)
2005
1951
2007
Long-term
outcomes (Schiffel/liaño)
RRT
Dosification (Ronco, Schiffl)
APACHE II (Knaus)
1990's1990
2000
ARF (Smith)
(Bellomo)
AKI
Clinical & epidemiological
cornerstones in ARF/AKI
Crush
syndrome (Bywaters)
Definition &
standardization
RIFLE (Bellomo)
1917
1941
19771973
1985
2004
War
nephritis (Weldon)
1st Acute
dialysis(Kolf)
Isolated
UF
(Bergström)
1st CAVHF (Kramer)
Biomarkers
(Mishra)
2005
1951ARF (Smith)
AKI
Beginning of
the cohort
studies
2007
Long-term
outcomes (Schiffel/liaño)
RRT
Dosification (Ronco, Schiffl)
APACHE II (Knaus)
(Bellomo)
1990's1990
2000
Clinical & epidemiological
cornerstones in ARF/AKI
Crush
syndrome (Bywaters)
Definition &
standardization
RIFLE (Bellomo)
1917
1941
19771973
1985
2004
War
nephritis (Weldon)
1st Acute
dialysis(Kolf)
Isolated
UF
(Bergström)
1st CAVHF (Kramer)
Biomarkers
(Mishra)
2005
1951ARF (Smith)
AKI
Beginning of
the cohort
studies
1st
Epidemio.
Study
2007
Long-term
outcomes (Schiffel/liaño)
RRT
Dosification (Ronco, Schiffl)
(Eliahou)
APACHE II (Knaus)
(Bellomo)
1990's1990
2000
Clinical & epidemiological
cornerstones in ARF/AKI
Crush
syndrome (Bywaters)
Definition &
standardization
RIFLE (Bellomo)
1917
1941
19771973
1985
2004
War
nephritis (Weldon)
1st Acute
dialysis(Kolf)
Isolated
UF
(Bergström)
1st CAVHF (Kramer)
Biomarkers
(Mishra)
2005
1951ARF (Smith)
AKI
Beginning of
the cohort
studies
1st
Epidemio.
Study
2007
Long-term
outcomes (Schiffel/liaño)
RRT
Dosification (Ronco, Schiffl)
(Eliahou)
APACHE II (Knaus)
(Bellomo)
1990's
1st
Epidemio.
Chapter
1990(Kleinknecht)
2000
Clinical & epidemiological
cornerstones in ARF/AKI
Crush
syndrome (Bywaters)
Definition &
standardization
RIFLE (Bellomo)
1917
1941
19771973
1985
2004
War
nephritis (Weldon)
1st Acute
dialysis(Kolf)
Isolated
UF
(Bergström)
1st CAVHF (Kramer)
Biomarkers
(Mishra)
2005
1951ARF (Smith)
AKI
Beginning of
the cohort
studies
1st
Epidemio.
Study
Multicentre
studies
2007
Long-term
outcomes (Schiffel/liaño)
RRT
Dosification (Ronco, Schiffl)
(Eliahou)
APACHE II (Knaus)
(Bellomo)
(Feest, Liaño,
Brivet)1990's
1st
Epidemio.
Chapter
1990(Kleinknecht)
2000
Clinical & epidemiological
cornerstones in ARF/AKI
Crush
syndrome (Bywaters)
Definition &
standardization
RIFLE (Bellomo)
1917
1941
19771973
1985
2004
War
nephritis (Weldon)
1st Acute
dialysis(Kolf)
Isolated
UF
(Bergström)
1st CAVHF (Kramer)
Biomarkers
(Mishra)
2005
1951ARF (Smith)
AKI
Beginning of
the cohort
studies
1st
Epidemio.
Study
Multicentre
studies
1st Use of
administrative
databases2007
Long-term
outcomes (Schiffel/liaño)
RRT
Dosification (Ronco, Schiffl)
(Eliahou)
APACHE II (Knaus)
(Bellomo)
(Feest, Liaño,
Brivet)1990's
1st
Epidemio.
Chapter
1990(Kleinknecht)
(Liangos, Waikar, Xue)
2000
Clinical & epidemiological
cornerstones in ARF/AKI
Crush
syndrome (Bywaters)
Definition &
standardization
RIFLE (Bellomo)
1917
1941
19771973
1985
2004
War
nephritis (Weldon)
1st Acute
dialysis(Kolf)
Isolated
UF
(Bergström)
1st CAVHF (Kramer)
Biomarkers
(Mishra)
2005
1951ARF (Smith)
AKI
Beginning of
the cohort
studies
1st
Epidemio.
Study
Multicentre
studies
1st Use of
administrative
databases
Epidemiological
Population-Based
Use of RIFLE
2007
Long-term
outcomes (Schiffel/liaño)
RRT
Dosification (Ronco, Schiffl)
(Eliahou)
APACHE II (Knaus)
(Bellomo)
(Feest, Liaño,
Brivet)1990's
1st
Epidemio.
Chapter
1990(Kleinknecht)
(Liangos, Waikar, Xue)
(Ali)
2000
Clinical & epidemiological
cornerstones in ARF/AKI
Crush
syndrome (Bywaters)
Definition &
standardization
RIFLE (Bellomo)
1917
1941
19771973
1985
2004
War
nephritis (Weldon)
1st Acute
dialysis(Kolf)
Isolated
UF
(Bergström)
1st CAVHF (Kramer)
Biomarkers
(Mishra)
2005
1951ARF (Smith)
AKI
Beginning of
the cohort
studies
1st
Epidemio.
Study
Multicentre
studies
1st Use of
administrative
databases
Epidemiological
Population-Based
Use of RIFLE
2007
Long-term
outcomes (Schiffel/liaño)
RRT
Dosification (Ronco, Schiffl)
Search
for new
issues
(Eliahou)
APACHE II (Knaus)
(Bellomo)
(Feest, Liaño,
Brivet)1990's
1st
Epidemio.
Chapter
1990(Kleinknecht)
(Liangos, Waikar, Xue)
(Ali)
2000
Préambule
Histoire
L'épidémiologie dans l'unité de soins
intensifs
Un appel de réveil
Une promenade dans
l'épidémiologie de l'insuffisance
rénale aiguë en quatre étapes:
Epidemiology of AKI in the ICU setting
Incidence and mortality
Time of development
Etiology
Early outcome
Late outcome
Epidemiology of AKI in the ICU setting
Incidence and mortality
Time of development
Etiology
Early outcome
Late outcome
Patients Initial Hospital Location
34%
23%2%
13%
1%
27%
Medical Dpts.
Surgical Dpts. Traumatology
Nephrology
Gynaecology
ICU
Liaño F et al. Kidney Int 1996; 50:811-818
WITH AKI:
1,738
ICU Incidence: 5.7 %
Uchino et al. JAMA 2005; 294: 813-818
Herrera et al. Med Intensiva 2006; 30:260-267
WITH AKI:
901
ICI Incidence: 5.7 %
AKI in critically-ill patients: Multicentre
prospective studies
PATIENTS ADMITTED
IN 54 ICU:
29,269
(Multinational)
PATIENTS ADMITTED
IN 43 ICU:
15,714
(National - Spain)
Incidence of AKI according to
age during a decade in Australia
Bagshaw SM et al. Critical Care 2007; 11:R68Median age: 64.1 (49-74)
Age in years
Effect of the level of serum creatinine concentration in AKI diagnosis in a series of 9,210 patients admitted to Brigham
and Women´s Hospital
Chertow G et al. J Am Soc Nephrol 16: 3365-3379, 2005
0
2
4
6
8
10
12
14
16
18
0.3-0.4 0.5-0.9 1.0-1.9 > 2.0
N= 1564
N = 885
N = 246
N = 105
Inci
de
nce
(%
)
SCr in mg/dl
PATIENTS ADMITTED IN
20 ICU:
91,254
1996-2005
Criteria: SCr>1.5 mg/dL
AKI
4,754
Incidence: 5.2 %
a) Bagshaw SM et al. Critical Care 2007; 11:R68
b) Bagshaw SM et al. Critical Care 2008; 12:R47
ICU Incidence of early AKI in the same
setting (ANZICS Database) varies with
definition
AKI
43,395
Incidence: 36.0 %
PATIENTS ADMITTED IN
57 ICU:
120,123
2000-2005
Criteria: RIFLE
a
b
Fracaso renal
agudo
Declining mortality in patients with acute renal failure,
1988 to 2002. Waikar SS et al. J Am Soc Nephrol 2006;
17: 1143-1150
0
5
10
15
20
25
30
35
40
45
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
Mo
rtal
ity
(%)
ARF with dialysis
ARF
Incidence: 1988 610/1,000,000 inhabitants
2002 2880/1,000,000 h
Fracaso renal
agudo
Declining mortality in patients with acute renal failure,
1988 to 2002. Waikar SS et al. J Am Soc Nephrol 2006;
17: 1143-1150
0
5
10
15
20
25
30
35
40
45
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
Mo
rtal
ity
(%)
ARF with dialysis
ARF
Incidence: 1988 610/1,000,000 inhabitants
2002 2880/1,000,000 hΔ 10 % YEARLY
Incidence of dialysis-requiring AKI
Hsu RK et al. J Am Soc Nephrol 2013. doi: 10.1681/ASN.2012080800
Incidence of dialysis-requiring AKI
Hsu RK et al. J Am Soc Nephrol 2013. doi: 10.1681/ASN.2012080800
Δ 10 % YEARLY
Mortality rate during a decade
for early AKI in a cohort of
Australian ICUs
Year
Mo
rta
lity
(%
)
AKI No AKI
Bagshaw SM et al. Critical Care 2007; 11:R68
Epidemiology of AKI in the ICU setting
Incidence
Time of development
Etiology
Early outcome
Late outcome
ICU Incidence of AKI using RIFLE
criteria
Hoste EAJ et al Critical Care 2006; 10: R73
Early AKI
22%
Late AKI 45%
ICU Incidence of AKI using RIFLE
criteria
Hoste EAJ et al Critical Care 2006; 10: R73
Early AKI
22%
Late AKI 45%
67 %
Epidemiology of AKI in the ICU setting
Incidence
Time of development
Etiology
Early outcome
Late outcome
TYPE OF AKI
Type (%) ICU n = 253
No-ICU n = 495
P
ATN
76
37 <0.001
Prerenal 18 28 0.002
Acute-on-Chronic
8 15 0.005
Obstructive 0,8 15 <0.001
ATIN 0 3 <0.001
Acute GN 2 4 0.325
Others 1,2 10 <0.001
Liaño F et al. Kidney Int Suppl 1998; 66:S16-S24
Causes associated with the
development of AKI in 1,726 critically-
ill patients
05
101520253035404550
Sep
tic s
hock
Surg
ery
Car
diogen
ic s
hock
Hyp
ovole
mia
Dru
gsHRS
Obs
truct
ive
Oth
ers
Uchino et al. JAMA 2005; 294: 813-818
Epidemiology of AKI in the ICU setting
Incidence
Time of development
Etiology
Early outcome
Late outcome
PREVIOUS
HEALTH
CONDITION
ORIGINAL
DISEASE
KIND AND
SEVERITY OF
KIDNEY INSULT
DEATH
RECOVERY
Baseline SCr
Acute response
Short-term outcome
Analysis of the cardiovascular co-morbility in ARF and non-ARF cases: an estimation in 29,039,599 hospitalised
patients in the USA during 2001
0
5
10
15
20
25
30
35
Coronary
Dis.
HF CKD HT Diabetes
ARF No ARF(558,032) (28,481,567)
*
*
*
*
*
*, p < 0.0001
Liangos O et al. Clin J Am Soc Nephrol 1: 43-51, 2006
Analysis of the cardiovascular co-morbility in ARF and non-ARF cases: an estimation in 29,039,599 hospitalised
patients in the USA during 2001
0
5
10
15
20
25
30
35
Coronary
Dis.
HF CKD HT Diabetes
ARF No ARF(558,032) (28,481,567)
*
*
*
*
*
*, p < 0.0001
Liangos O et al. Clin J Am Soc Nephrol 1: 43-51, 2006
HRs for in-Hospital Mortality by
Baseline CKD and AKI status
eGFR (ml/min/1.7m2)
HR
Pannu N et al. Am J Kidney Dis 2011; 58:206-21340,000 pats.
PREVIOUS
HEALTH
CONDITION
ORIGINAL
DISEASE
KIND AND
SEVERITY OF
KIDNEY INSULT
DEATH
RECOVERY
Baseline SCr
Acute response
Short-term outcome
Mortality in ICU: 30 -80%
Incidence and outcomes of AKI in
intensive care units: A veterans
administration studyThakar CV et al. Crit Care Med 2009; 37: 2552-2558
• Retrospective observational study in a
national cohort of 325,398 pats. Admitted
to 191 ICUs (2001-2006).
• AKI: AKIN classification
• ICU evaluated by a VA system
Incidence and outcomes of AKI in
intensive care units: A veterans
administration studyThakar CV et al. Crit Care Med 2009; 37: 2552-2558
Odds of death by severity of AKI
Aki stage Odds
ratio
95% CI
I 2.23 2.17- 2.30
II 6.08 5.74-6.44
III 8.6 8.08-9.15
III -RRT 5.78 5.30-6.31
326,395 ICU pats
71,486 AKI
3,140 needed RRT.
(22 %)
(4.4 %)
PREVIOUS
HEALTH
CONDITION
ORIGINAL
DISEASE
KIND AND
SEVERITY OF
KIDNEY INSULT
DEATH
RECOVERY
Baseline SCr
Acute response
Short-term outcome
Length of AKI
Mortality rates by magnitude and length of
Acute Kidney Injury
Coca et al. Kidney Int 2010; 78:926-933
35,302 Postoperative diabetic
pats. (non cardiac sur). VA data
AKI:18%
ICU information not provided
Epidemiology of AKI in the ICU setting
Incidence
Time of development
Etiology
Early outcome
Late outcome
PREVIOUS
HEALTH
CONDITION
ORIGINAL
DISEASE
KIND AND
SEVERITY OF
KIDNEY INSULT
DEATH
RECOVERY
DEATH
Baseline SCr
Acute response
Short-term outcome
Long-term outcome
TOTAL Recov.
CKD?
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
1 2 3 4 5 6 7 8 9 10111213141516171819202122
p=0.002
Years
Cu
mu
lati
ve
Su
rviv
al
Ra
te
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
1 2 3 4 5 6 7 8 9 10111213141516171819202122
ICU
patients
Non ICU
patients
LONG-TERM ATN SURVIVAL CURVES:
ICU vs NON-ICU PATIENTS
Liaño F et al. Kidney Int 2007; 71:679-686
Reference
Value
Regresion
Coefficient p
Relative
Risk
Confidence
Interval
AGE 0.05 0.000 1.05 1.03-1.07
Co-morbid Factors
Absent 1.40 0.009 4.08 1.42-11.7
Type of
admission:
Surgical
Medical
-0.68
0.002
0.50
0.33-0.78
Non-Oliguric ARF
Oliguric ARF
-0.69 0.005 0.50 0.31-0.80
FACTORS ASSOCIATED WITH LONG-TERM
MORTALITY IN ATN:
ATN: LONG-TERM OUTCOME
Risk of Chronic Dialysis and All-Cause of
Mortality in AKI-dialysed patients and
matched patients without AKI
Wald et al. JAMA 2009; 302: 1179
Risk of Chronic Dialysis and All-Causes of
Mortality in AKI-dialysed patients and
matched patients without AKI
Wald et al. JAMA 2009; 302: 1179
Lancet 2010; 376:2096-2103
Rate ratios of mortality and ESRD following AKI:
Mortality ESRD or doubling SCr
RR (95 %CI) of AKI patients
RR (95 %CI) of patients w/o AKI900,000 patients
Préambule
Histoire
L'épidémiologie dans l'unité de soins
intensifs
Un appel de réveil
Une promenade dans
l'épidémiologie de l'insuffisance
rénale aiguë en quatre étapes:
Chronic
Dialysis
ESKDAKI
Death DeathDeath
Recovery Recovery
From AKI to ESKD: could this
hypothesis be true?
AKI
Chronic
Dialysis
ESKD
Death DeathDeath
Recovery Recovery
From AKI to ESKD: could
this hypothesis be true?
100%
50%
At discharge
Alive 50 %
Follow-up: 5 yr
With CKD: range 14-61 (%)
Alive: 50 - 70 % of survivors
Follow-up: 5 yr
On RRT 1% of survivors
With data from : Ponte B et al. NDT 2008; 23 3859 & Schiffl H et al. NDT 2008; 23: 2235
Kidney Int 2012; 81:477-485
Methods:
• Propensity score-matched cohort. retrospective analysis
• Pennsylvania. (2004-2007)
• Populations:
• Patients dicharged alive 30,207
• Reversible AKI: 1,997. (Critical Care: 18%)
• Length of AKI: ≤ 24 h: 75%
• Matched: 1,610 AKI vs 3,652 control pats.
• Excluded:
– eGFR ≤ 60 ml/min/1.73 m2
– Hematuria and /or proteinuria
Kidney Int 2012; 81:477-485
Cumulative incidence of CKDLong-term survival
Adjusted risk of mortality:
HR 1.18 (CI 95%; 0.9-1.46)
Risk of de novo CKD:
HR 1.91 (CI 95%; 1.75-2.09)
9,5
17,4
4,6
7
7
8,1
16,3
59.3
0 10 20 30 40 50 60
Unknown
Other causes
Hepatic failure
Infection
Respiratory Insufficiency
Neurological
Cardiac
Cause of ATN admission
%
Causes of Mortality during the follow-upATN LONG-TERM OUTCOME:
Liaño F et al. Kidney Int 2007; 71:679-686
Une promenade dans
l'épidémiologie de l'insuffisance
rénale aiguë en quatre étapes
• The different epidemiological approaches, cohort, multicentre, population-based and administrative databases provide complementary information
• Serum creatinine is the main tool used in the epidemiological studies
Summary I
• Incidence of AKI in the ICU is high and higher than in other settings
• Incidence rates vary according to the definition used
• Mortality remains high even though a trend to decrease has been observed
• AKI is more frequent among older patients
Summary II
Une promenade dans
l'épidémiologie de l'insuffisance
rénale aiguë en quatre étapes
• CKD and other comorbidities contribute to development of AKI
• AKI seems to facilitate progression to CKD and death
• Comorbidities also influence long-term outcome and could be behind the progression to CKD and death
Summary III
Une promenade dans
l'épidémiologie de l'insuffisance
rénale aiguë en quatre étapes