Management and prognosis of
acute kidney injury
1
CASE PRESENTATION
A 48-year-old woman with
vomiting with blood clot for 10
days
2
PAST HISTORY

Systemic disease
Hypertension for 10+ year
 Chronic hepatitis B related liver cirrhosis, Child A
 Coronary artery disease, s/p POBA
 Peptic ulcer disease


Regular medications
Inderal(10mg) 1# BID
 Norvasc(5mg) 1# BID

3
PRESENT ILLNESS
2011/2/25

Chronic hepatitis B with flare up


2011/3/02
Start Lamivudine
Hepatic encephalopathy
Switch to Entecavir
 Start pre-liver transplantation evaluation

4
AST
ALT
U/O
T-Bil
1600
1400
45
1500
40
0222
1200
0310
0323 35
30
1000
25
800
20
600
400
15
500
10
200
5
0
0
2011/3/6~3/21
Plasma
Exchange
2011/3/10~
SLED
5
NTUH ICU PROTOCOL
6
U/O
0310
2011/3/23
Liver
U/O
BW
Transplantation
SLED
7
1600
1400
1200
1000
800
600
400
200
0
2011/2/28
2011/3/2
2011/3/4
2011/3/6
2011/3/8
2011/3/10
2011/3/12
2011/3/14
2011/3/16
2011/3/18
2011/3/20
2011/3/22
2011/3/24
2011/3/26
2011/3/28
2011/3/30
2011/4/1
2011/4/3
2011/4/5
2011/4/7
2011/4/9
2011/4/11
2011/4/13
2011/4/15
0222
0323
0406
2011/3/10~
SLED cSLED(4/3-4/12)SLEDIHD
0418
95
90
85
80
c- SLED
75
70
BW
2011/3/23
Liver Transplantation
BUN
Cr
80
8
70
6.72
7
67
60
5.6
50
40
4
4.43
6
5
4
30
3
20
2
10
0
SLED
1
c- SLED
2011/3/10~
SLED cSLED(4/3-4/12)SLED IHD
0
8
2011/3/23
Liver
Transplantation
AST
ALT
U/O
T-Bil
2011/4/06
Explore laparotomy
Liver biopsy: no rejection
1600
1400
45
40
35
1200
30
1000
25
800
20
600
400
200
15
SLED
10
c- SLED
5
0
2011/3/6~3/21
Plasma
Exchange
2011/3/10~
SLED cSLED(4/3-4/12)SLED IHD(-5/6)Hold
0
9
INDICATION AND TIMING OF DIALYSIS FOR AKI
RENAL REPLACEMENT VS RENAL SUPPORT
Renal replacement
Purpose
Timing of intervention
Replace renal function
Based on level
biochemical markers
Fluid removal
Indications for dialysis Narrow
Dialysis dose
Extrapolated from
ESRD
Renal support
Support other organs
Based on individual
Fluid removal
Cytokines
Broad
Targeted for overall
support
Buy time
10
11
MEDLINE search for ARF / AKI
AKI and prognosis
治療
預測
透析
預後
14
All cause of mortality, 11830 patients, mean follow up for 4.73 years
sRIFLE
How about long term outcomes?
CKD was defined according to
estimated glomerular filtration rate
(eGFR) ≦ 45 mL/min/1.73m2
15
Acute on chronic KD, long term mortality
All cause of mortality, 11830 patients, mean follow up for 4.73 years
16
R
I
F
17
Geriatric AKI- diagnosis dilemma
Azotemia is poor prognosis
18
Recovery from advanced AKI
•
2956 AKI-dialysis form 5083 sampled patients, 685 (23.2%) patients could
withdraw from acute dialysis for at least 90 days.
Wu VC, et al, in prepare, 2012
19
AKI and prognosis
藥物治療
透析治療
預後
Ronco C
21
22
CARDIO-RENAL SYNDROME
ECMO
C-SLED-f, CVVH
23
Pre-Operative Proteinuria and Adverse Renal Outcomes in
Patients Receiving Coronary Artery Bypass Grafting Surgery.
24
Huang , Wu el al,JASN, 2011
POST-OPERATIVE AKI, RRT AND
30 DAY’S ALL CAUSE MORTALITY
mild (trace to 1+) or heavy (2+ to 4+)
25
Huang DM, Wu VC et al, JASN, 2011
ADVERSE OUTCOME OF CABG
Post operative AKI
Post operative RRT
26
Huang , Wu et al, JASN, 2011
PROTEINURIA PREDICT LONG TERM
RRT AND MORTALITY AFTER CABG
Follow up 4.7 yrs
27
Wu VC et al, PLos one , 2012
LONG TERM CATASTROPHIC OUTCOME
STRATIFIED BY CKD STAGE AND
PROTEINURIA
28
Wu et al, PLos one, 2012
Potential role of new
biomarkers
Complications
Normal
Increased
Damage
risk
↓GFR
Kidney
failure
Death
Delayed biomarker for AKI
New biomarker is needed:
Early diagnosis
Define etiology
Predict outcome
↑BUN
↑Creatinine
Vaidya et al. Annu Rev pharmaco Toxico
2008;48:463-93
29
Factors influence steady state
creatinine in AKI
Muscle
mass
Nutrition
Sepsis
Edema
Protein metabolism
Volume of
distribution
Plasma creatinine
Drugs
Renal excretion
Tubular excretion
Nonlinear
Filtration (GFR)
Star et al. Kid Int 1998;54:1817-31
30
Biomarker of kidney injury
CS: Cardiac surgery
CN: contrast nephropathy
KT : kidney transplantation
SE: sepsis
Urinary sHJV is identified by proteomic approach
Hemojuvenin
BMP6, mHJV and Hepcidin co-orchestrate iron metabolism
HJV (or RGMc)
1.member of the repulsive
guidance molecules (RGM)
family,
2. membrane-bound and soluble
protein
3. highly expressed in liver,
skeletal muscles and heart.
sHJV↑
Hepcidin↓
Iron↑
Nature Genetics 41, 386 - 388 (2009)
Several ATN models induce the expression of renal HJV
Glycerol-Induced ATN
150
200
30000
Creatine Kinase
Serum Creatinine
3
2
10000
1
0
36 12 24
48
72
120
Post injection (hr)
0
168
(mg/dL)
100
20000
1.5
300
100
Blood Urine Nitrogen
50
1.0
0.5
Scrum creatinine
0
36 12 24
48
96
Post injection (hr)
0.0
168
Serum creatinine
(mg/dL)
Blood Urine Nitrogen
Blood Urine Nitrogen
(mg/dL)
Creatine Kinase
(Unit/L)
40000
Folic acid-Induced ATN
HJV is predominantly expressed in proximal renal tubules
Fold change of AKI biomarkers among Normal, AKI, CKD, UTI
and Rhabdomyolysis patients
2012, Kidney international
Furin inhibitor suppress the iron deposition and improve renal
function under renal I/R injury
**
200
*
150
100
50
0
Sham
12
2.0
Scr (mg/dL)
BUN (mg/dL)
250
**
*
1.5
1.0
0.5
0.0
24
Sham
Post I/R injury (hr)
150
*
50
12
24
Post I/R injury (hr)
Iron concentration
(mg/kg)
Iron concentration
(mg/kg)
**
0
24
Liver
200
0
12
Post I/R injury (hr)
Kidney
100
Sham
PBS
Furin inhibitor
200
sham
PBS
Furin inhibitor
HJV
150
100
50
0
0
12
24
Post I/R injury (hr)
2012, Kidney international
HJV predicts AKI
Biomarker in AKI
39