Une promenade dans l'épidémiologie de l'insuffisance ... · PDF...

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


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

Préambule

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intensifs

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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



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


RRT


APACHE II (Knaus)

1990's1990

2000

ARF (Smith)

(Bellomo)

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


RRT


APACHE II (Knaus)

(Bellomo)

1990's1990

2000



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


RRT


(Eliahou)

APACHE II (Knaus)

(Bellomo)

1990's1990

2000



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


RRT


(Eliahou)

APACHE II (Knaus)

(Bellomo)

1990's

1st

Epidemio.

Chapter

1990(Kleinknecht)

2000



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


RRT


(Eliahou)

APACHE II (Knaus)

(Bellomo)

(Feest, Liaño,

Brivet)1990's

1st

Epidemio.

Chapter

1990(Kleinknecht)

2000



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


RRT


(Eliahou)

APACHE II (Knaus)

(Bellomo)

(Feest, Liaño,

Brivet)1990's

1st

Epidemio.

Chapter

1990(Kleinknecht)

(Liangos, Waikar, Xue)

2000



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


RRT


(Eliahou)

APACHE II (Knaus)

(Bellomo)

(Feest, Liaño,

Brivet)1990's

1st

Epidemio.

Chapter

1990(Kleinknecht)


(Ali)

2000



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


RRT


Search

for new

issues

(Eliahou)

APACHE II (Knaus)

(Bellomo)

(Feest, Liaño,

Brivet)1990's

1st

Epidemio.

Chapter

1990(Kleinknecht)


(Ali)

2000

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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


Incidence of dialysis-requiring AKI


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


Incidence

Time of development

Etiology

Early outcome

Late outcome

AKI can develop in:

Community

Hospital Ward

ICU

AKI can develop in:

Community

Hospital Ward

ICU

Early AKI

Late AKI

ICU Incidence of AKI using RIFLE

criteria

Hoste EAJ et al Critical Care 2006; 10: R73


criteria


Early AKI

22%

Late AKI 45%


criteria


Early AKI

22%

Late AKI 45%

67 %


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


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

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


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


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

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AKI CKD

?

Chronic

RRT

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)

CKD and Long-term AKI outcome

Triverio PA et al. Nephrol Dial Transplant 2009; 24: 2186-89

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:


Une promenade dans



• 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

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• 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

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Thank you

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