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Acute Kidney Injury (AKI) Klassificering
Epidemiologi
Genes
Prognos
Njurskademarkrer
Max Bell, MD, PhD / Johan Mrtensson, MD, PhD Dept of Anaesthesia and Intensive Care Karolinska University Hospital Solna
karolinska intensive care nephrology group
1
AKI kontinuum
Identify risk Identify injury Monitor injury & repair Monitor outcome
GFR drop
Creatinine rise
Primary prevention
Secondary prevention (post biomarker change)
Renal replacement therapy
Injury evolution time
Nor
mal
Death ESKD Partial recovery Full recovery
2
AKI kontinuum
Identify risk Identify injury Monitor injury & repair Monitor outcome
GFR drop
Creatinine rise
Primary prevention
Secondary prevention (post biomarker change)
Renal replacement therapy
Injury evolution time
Nor
mal
Death ESKD Partial recovery Full recovery
3
Hur stort r problemet? Historiskt sett har incidensen varit svr att beskriva. *IVA-incidens: 1-31%
*Varierande definitioner; 25% kning av kreatinin till behov av dialys
Svr AKI behov av dialys p IVA frekommer i ca 5% av IVA-populationen
Uchino, S., et al.: Acute renal failure in critically ill patients: a multinational, multicenter study. Jama 2005; 294:813-8.
Incidensen har kat under de senaste 20 ren, frn 61 till 288 per 100,000 (AKI) och frn 4-27/100,000 (Svr AKI)
Waikar, S.S., et al.: Declining mortality in patients with acute renal failure, 1988 to 2002. J Am Soc Nephrol 2006; 17:1143-50
En rlig kning av incidensen med 11% rapporteras. Xue JL et al. Incidence and mortality of acute renal failure in Medicare beneficiaries, 19922001. J Am Soc Nephrol 2006;17:11351142
Epidemiologin fr akut njursvikt (AKI, Acute Kidney Injury) har saknat en enhetlig klassifikationsmodell.
I en genomgng av studier fann Novis et al 35 (!) olika definitioner
av akut njursvikt. Novis BK, Roizen MF, Aronson S, Thisted RA (1994) Association of preoperative risk factors with postoperative acute
renal failure. Anesth Analg 78:143-149.
tgrder frn ADQI/AKIN-grupperna kom 2002-2004 och 2007 med RIFLE/AKIN
Dessa gemensamma klassifikationer r nu validerade p ver 500.000 patienter
I en IVA-kohort p 5383 patienter i USA utvecklade 2/3 AKI 12.4% hade maximalt RIFLE Risk, 26.7% hade maximalt RIFLE Injury och 28.1% hade maximalt RIFLE Failure
Hoste, E.A., et al.: RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a
cohort analysis. Crit Care 2006; 10:R73
Genes Multifaktoriellt. ven fr en och samma patient. Komorbiditeter
bidrar! Grovt: sepsis, ischemi och nefrotoxiska lkemedel Sepsis strst orsak p generella IVA
Post CABG (ischemi): AKI vanligt frekommande, nstan patienter utvecklar syndromet.
DOnofrio et al. RIFLE Criteria for Cardiac SurgeryAssociated Acute Kidney Injury: Risk Factors and Outcomes, Congest Heart Fail. 2010 Jul;16 Suppl 1:S32-6.
Svr AKI (screa 300 mol/l och/eller urea 40 mmol/l under frsta 24 timmarna efter intag) extraherades frn den brittiska ICNARC CMP databasen p 276,326 intag frn 1995 till 2004 Svr AKI hos 17,326 av 276,731 intag (6.3%) Sepsis hos 47.3% av AKI fallen Kolhe et al. Crit Care 2008;12(suppl 1):S2
B.E.S.T. Kidney study 29269 patienter screenade p 52 IVA frn 23 lnder 1,758 med svr AKI (urea > 30 mmol/L eller UO
Patofysiologi
11
r AKI farligt?
2202 pa(enter med akut dialys, 32 IVA, 1995-2004 ESRD pa(enter exkluderade 1102 pa(enter levde vid 90 d Signifikant skillnad avseende risk fr kroniskt dialysberoende vid 90d: CRRT 8%, IHD 17% Justerat odds raEo fr IHD var 2.6 (1.5-4.3)
LngEdsverlevnad straEfierat fr CKD/AKI
Acute-on-chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality. Wu VC et al, Kidney Int. 2011 Dec;80(11):1222-30
AKI och morbiditet: ESRD e^er AKI
Acute-on-chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality. Wu VC et al, Kidney Int. 2011 Dec;80(11):1222-30
CKD och ESRD e^er AKI, systemaEsk review
CKD
ESRD
Chronic kidney disease a^er acute kidney injury: a systemaEc review and meta-analysis. Coca SG et al. Kidney Int. 2011 Nov 23
ESRD e^er AKI, B.E.S.T.
ESRD e^er postoperaEve AKI
The 90-day mortality and the subsequent renal recovery in criEcally ill surgical paEents requiring acute renal replacement therapy. Lin YF et al. Am J Surg. 2009 Sep;198(3):325-3
diagnos(k
AKI kontinuum
Identify risk Identify injury Monitor injury & repair Monitor outcome
GFR drop
Creatinine rise
Primary prevention
Secondary prevention (post biomarker change)
Renal replacement therapy
Injury evolution time
Nor
mal
Death ESKD Partial recovery Full recovery
21
Historik
Period Acute myocardial injury Acute kidney injury
1960s LD, ASAT, ALAT Creatinine, urine output
1970s CK-B, myoglobin Creatinine, urine output
1980s CK-MB Creatinine, urine output
1990s Troponin-T Creatinine, urine output
2000s Troponin-I Creatinine, urine output
Improved therapies Reduced mortality
Supportive treatment High mortality
22
Kreatinin
Kreatinin Sen respons Plasmanivn stiger frst nr GFR halverats1
Sannolikt pga kompensatorisk utsndring via tubuli och tarm Ref: 1Levey et al. Ann Rev Med 1988
23
Kreatinin
253 IVA patienter med AKI SCr justeras fr ackumulerad vtskebalans Hos 25% av patienterna noterades en 50%-ig kreastegring minst ett dygn tidigare vid justering fr vtskebalansen Krea underskattas ca 2%/liter ackumulerad vtska
24
Kreatinin
20
15
10
5
0
5 Weight change (%)
40
30
20
10
0
10
20
30
40
50
60
Cys
tatin
C &
cre
atin
ine
chan
ge (%
)
1 2 3 4 5 6 7ICU day
20
15
10
5
0
5
Wei
ght c
hang
e (%
)
40
30
20
10
0
10
20
30
40
50
60
Cys
tatin
C &
cre
atin
ine
chan
ge (%
)
1 2 3 4 5 6 7ICU day
CreatinineBody weight
A B
20
15
10
5
0
5 Weight change (%)
40
30
20
10
0
10
20
30
40
50
60
Cys
tatin
C &
cre
atin
ine
chan
ge (%
)
1 2 3 4 5 6 7ICU day
20
15
10
5
0
5
Wei
ght c
hang
e (%
)
40
30
20
10
0
10
20
30
40
50
60
Cys
tatin
C &
cre
atin
ine
chan
ge (%
)
1 2 3 4 5 6 7ICU day
CreatinineBody weight
A B20
15
10
5
0
5 Weight change (%)
40
30
20
10
0
10
20
30
40
50
60
Cys
tatin
C &
cre
atin
ine
chan
ge (%
)
1 2 3 4 5 6 7ICU day
20
15
10
5
0
5
Wei
ght c
hang
e (%
)
40
30
20
10
0
10
20
30
40
50
60
Cys
tatin
C &
cre
atin
ine
chan
ge (%
)
1 2 3 4 5 6 7ICU day
CreatinineBody weight
A B
231 IVA patienter utan AKI Plasma kreatinin sjnk ca 25% frsta
veckan (ca 4%/dygn)
Kontinuerlig frlust av muskelmassa hos IVA patienter i tidigare studier (ca 2-4%/dag)1, 2
1Griffiths. Nutrition 1996;12: 456-458 2Reid et al. Clinical Nutrition 2004;23: 273-280
25
Cystatin C
Cystatin C 13 000 Da (>100 ggr strre n krea)
1/3 av kreas Vd (= ECV)
Filtreras fritt
terresorberas och kataboliseras i
tubuli
Produceras i alla krnfrande celler
26
Cystatin C
Tidigare frisk, 69 rig kvinna med svr sepsis.
1
1.5
2
2.5
3
Pla
sma
cyst
atin
C (m
g/L)
50
70
90
110
Pla
sma
crea
tinin
e (m
icro
mol
/L)
0 1 2 3 4 5 6ICU day
CreatinineCystatin C
20
40
60
80
100
120G
FR
0 1 2 3 4 5 6ICU day
Cystatin C GFRMDRD GFRCockcroft-Gault GFR
27
Cystatin C
85 IVA patienter (50% med AKI). Cystatin C steg > 50% ca 1,5 dygn tidigare n kreatinin. En 50%-ig kning av cys C predikterade RIFLE. AuROC 0.82 on AKI day -2 AuROC 0.97 on AKI day -1
100
150
200
250
Rel
ativ
e A
KI d
ay -3
(%)
-3 -2 -1 0AKI day
Cystatin CCreatinine
1.5 d
28
Cystatin C
10
5
0
5
Wei
ght c
hang
e (%
)
80
40
0
40
80
120
160
200
240
Cys
tatin
C &