Thai Transplant Care (TTC) Kidney

THAI TRANSPLANT CARE (TTC)
KIDNEY
Thai Transplantation Society

September 2014
TTC: Kidney (September, 2014)

Thai Transplant Care (TTC)

..

Thai Transplant Care

Kidney Disease: Improving Global Outcomes (KDIGO)

2

Thai Transplant Care (TTC)

KDIGO .. 2009

(World Health Assembly)

4


(Glossary)
11
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12
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1.................................................................................................................................................................................................
13
2.................................................................................................................................................................................................
Induction Therapy
17
3.................................................................................................................................................................................................
Maintenance Therapy
20
4.................................................................................................................................................................................................
Acute Rejection
23
5.................................................................................................................................................................................................
Chronic Allograft Nephropathy/Injury (CAN/CAI)
28
6.................................................................................................................................................................................................
CMV
32
7.................................................................................................................................................................................................
35
Index
40
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10
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(Glossary)
ATG
CAN/CAI
CMV
DFPP
DGF
DSA
ECD
HLA
HR
IL-2RA
IVIg
KDIGO
LR
MM
MR
mTOR
PP
PRA
TTC
VHR
VLR
Antithymocyte globulin
Chronic Allograft Nephropathy/Injury
Cytomegalovirus
Double Filtration Plasmapheresis
Delayed Graft Function
Donor Specific Antibody
Expanded Criteria Donor
Human Leukocyte Antigen
High Risk
Interleukin 2 receptor antagonist
Intravenous Immunoglobulin
Kidney Disease: Improving Global Outcomes
Low Risk
Mismatch
Moderate Risk
Mammalian Target of Rapamycin
Plasmapheresis
Panel Reactive Antibody
Very High Risk
Very Low Risk
11
12
1
2
A
B
C
D
1.

(.) .. 2551

Kidney Disease: Improving
Global Outcomes (KDIGO)

(1) (2)
(3) (4)
(5) European
Renal Best Practice KDIGO (6)
5
Induction Therapy, Maintenance Therapy, Acute Rejection,
Chronic Allograft Nephropathy/Injury (CAN/CAI) Cytomegalovirus (CMV) 18
13

KDIGO (7)
rejection
14
1.1: Acute Rejection

1.1.1: (Very Low Risk; VLR)
Human Leukocyte Antigen
(HLA) typing zero mismatch (0-MM) Panel Reactive
Antibody (PRA) 0
1.1.2: (Low Risk; LR)
( 0-MM HLA-DR, HLADQ, HLA-DP mismatch) PRA 0-10
HLA typing zero
mismatch (0-MM) PRA 0-10
1.1.3: (Moderate Risk; MR)
( 0-MM) PRA 10-50
( 0-MM) PRA 1050

HLA-DR mismatch
HLA-DQ mismatch HLA-DP mismatch
1.1.4: (High Risk; HR)

( 0-MM) PRA
50
( 0-MM) PRA
50
15
Expanded Criteria (ECD)

20
specific antibody Luminex PRA negative
cross match
1.1.5: (Very High Risk; VHR)
positive cross match
ABO blood group incompatibility
1.2:
1.1
(VLR)
(LR)
(MR)
(HR)
(VHR)
16
PRA
HLA typing
Cross matching
2. Induction Therapy
Induction therapy

2.1:
2.1.1: (VLR) antibody induction
2.1.2: (LR) antibody induction interleukin 2 receptor antagonist (IL-2RA)
(
2.1)
PRA 10 antibody induction [2C] IL-2RA [2B]
( 1-MM HLA-DR mismatch) PRA 0 antibody induction
[2C] IL-2RA [2B]
HLA typing zero
mismatch (0-MM) antibody induction [2D]
IL-2RA [2B]
2.1.3: (MR) IL-2RA
antithymocyte globulin (ATG)
PRA 10-50 IL-2RA [1B] ATG [2B]
IL-2RA [1B] ATG [2B]
17
2.1 Induction Therapy
(VLR)
(LR)
(MR)
(HR)
(VHR)
IL-2RA
ATG
Precondition
N*
Y [2B]
Y [1B]
Y [2B]
Y [2C]
N*
N*
Y [2B]
Y [2B]
Y [2B]
N*
N*
N*
Y [2D]
Y [2A]
* Not Graded
HLA-DR mismatch IL-2RA [1B] ATG [2B]

HLA-DQ mismatch HLA-DP mismatch IL2RA [2B] ATG [2D]
2.1.4: (High Risk; HR) IL-2RA
ATG
IL-2RA [2B]
ATG [2B]
Expanded Criteria (ECD)
IL-2RA [2B] ATG [2B]
PRA 50 IL-2RA [2B] ATG
[2B]
20 IL-2RA [2B] ATG [2C]
Specific Antibody Luminex PRA negative
cross match IL-2RA [2B] ATG [2B] desensitization [2D]
18
2.1.5: (VHR) desensitization

precondition IL-2RA ATG
ABO incompatibility ATG [2B] IL-2RA [2A]
positive cross match ATG [2B] IL-2RA [2B]
2.2: methylprednisolone
2.3: (VHR) precondition
induction
Anti-CD20 antibody (Rituximab)
Plasmapheresis (PP) double-filtration plasmapheresis (DFPP)
Intravenous immunoglobulin (IVIg)
Tacrolimus day -7 to day 0
Mycophenolate day -7 to day 0
Methylprednisolone
2.4: Induction therapy
Basiliximab 20 mg/dose 0 4
Thymoglobulin 1-1.5 mg/kg/day 7 ATG-Fresenius 35 mg/kg/day 7
2.5: precondition
Methylprednisolone 500-1,000 mg/day 3
PP DFPP 1-1.5 plasma volume 5
IVIg 0.1-0.4 g/kg/dose PP DFPP
Rituximab 375 mg/m2 1-2 doses
19
3. Maintenance Therapy
3.1: calcineurin
inhibitor anti-proliferative agent steroid [1B]
3.1.1: calcineurin inhibitor first-line [2A]
Tacrolimus
[2D]
Cyclosporine
[2B]
3.1.2: mycophenolate anti-proliferative agent
[2B]
3.1.3: tacrolimus / prolonged-release tacrolimus
calcineurin inhibitor (MR)
(HR) (VHR)
3.1.4:
steroid (VLR) (LR)
IL2-RA steroid
(severe osteoporosis)
Avascular necrosis of bone
6
3.2: Acute
Rejection [2C]
20
3.2.1: calcineurin inhibitor

[2B]
3.2.2: prednisolone
(VLR) [2C]
3.2.3: calcineurin inhibitor Mammalian
Target of Rapamycin (mTOR) inhibitor
Hemolytic Uremic Syndrome (HUS)
calcineurin inhibitor
3.2.4: mTOR inhibitor
[1B]
3.3:
3.3.1: calcineurin inhibitor
[1B]
3.1 Maintenance Therapy
Regimens
CsA + MPA + Pred
CsA + MPA + Pred
Tac + MPA + Pred
Sirolimus + MPA + Pred
Everolimus + MPA + Pred
Methods
0-3 mo
3-6 mo 6-12 mo >12 mo
C0 (ng/ml) 200-300 150-200 120-150 75-100

C2 (ng/ml) 1300-1500 900-1200 700-900 500-700
C0 (ng/ml) 8-12
8-10
6-8
4-6
C0 (ng/ml) 5-12
4-8
4-8
4-8
C0 (ng/ml) 5-12
4-8
4-8
4-8
21

[2C]
[2C]
rejection
[2C]
3.3.2: cyclosporine 12-hour trough (C0)
2-hour post-dose (C2) [Not Graded]
3.3.3: tacrolimus 12-hour trough (C0)
[2C] prolonged-release tacrolimus 24-hour trough (C0)
[2C]
3.3.4: mTOR inhibitor 12-hour trough
2
everolimus [2C] 24-hour trough
5-7 sirolimus [2C]
22
4. Acute Rejection
(4, 8-18)
creatinine [1C]
Delayed Graft Function (DGF) [2C]
1-2
[2D]
4.2:
acute rejection [1C] (9, 10, 12, 14,
15)
4.3: Subclinical borderline rejection [2D]
(9, 10, 12, 14, 15)
4.4: pulse methylprednisolone T-cell mediated
acute cellular rejection first line [1D] (4, 18)
4.4.1: steroid acute cellular rejection
steroid [2D]
4.4.2: steroid recurrent/severe acute
cellular rejection (Banff Grade IIA ) ATG
[2C]
23
4.5: Acute Antibody-mediated Rejection

steroid [2C] (13, 17)
PP DFPP
IVIg
Anti-CD20 antibody (Rituximab) proteasome inhibitor (Bortezomib)
ATG
4.6: DSA /
[2C]
4.6.1: (VHR) DSA /
3 1
4.6.2: (HR) (MR)

DSA 3 1 DSA
4.6.3: (LR) DSA 1

/

4.7: DSA 1

/

24
mycophenolate
mycophenolate azathioprine
azathioprine mycophenolate [2D] (16)
tacrolimus prolonged release tacrolimus
tacrolimus cyclosporine tacrolimus / prolonged release tacrolimus [2D] (8, 11)
calcineurin inhibitors mTOR inhibitor
mTOR inhibitor calcineurin inhibitor tacrolimus
prolonged release tacrolimus [2D] (4)
Methylprednisolone 500-1,000 mg/day 10-15 mg/kg/day 35
Thymoglobulin 1-1.5 mg/kg/day 7 ATG-Fresenius 35 mg/kg/day 7
PP DFPP 1-1.5 plasma volume 7

IVIg 0.1-0.4 g/kg/dose PP DFPP 2 g/kg/
dose 1 dose
Rituximab 375 mg/m2 1-2 doses 1-2 Bortezomib
1.3 mg/m2/dose 1, 4, 8 11
25
4.1 Acute Cellular Rejection
4.2 Acute Antibody-mediated Rejection

26
4.3 Chronic Antibody-mediated Rejection
27
5. Chronic Allograft Nephropathy/Injury (CAN/

CAI)
(Chronic Allograft Nephropathy; CAN)

Interstitial Fibrosis Tubular Atrophy (IF/TA)
(Chronic
Allograft Injury; CAI)
(7, 19)
5.1:

[1B] (20)
(Ultrasonography)
(Doppler Color Flow)
DSA
BK
5.2:
[1C]
5.3: calcineurin
inhibitor mTOR inhibitor
[2C] (4, 7)
5.3.1: calcineurin inhibitor mTOR
inhibitor CAN/CAI eGFR 40 mL/min/1.73 m2
28
800 mg/g creatinine [2D] (4, 7)

5.3.2: azathioprine mycophenolate
CAN/CAI mTOR inhibitor
eGFR 40 mL/min/1.73 m2
800 mg/g creatinine [2D] (21, 22).
5.3.3 calcineurin inhibitor
positive DSA
de novo DSA (23, 24)

PRA >50%
HLA-DR HLA-DQ mismatch
HLA mismatch
( 20 )

rejection

antibody-mediated rejection (25)
29
5.1 CAN/CAI
Calcineurin inhibitor + High immunologic

risk
Mycophenolate
Calcineurin
inhibitor
50%
Creeping
Creatinine1
Recipient with
unfavorable factors
of mTOR inhibitor*
mTOR inhibitor +
Moderate
Calcineurin inhibitor immunologic risk
Minimization
70-90%
ASCERTAIN2 (ns)
mTOR inhibitor +
Mycophenolate
100%
CONVERT3
CONCEPT4
ASCERTAIN2
STN5 (ns)
post-CONCEPT6
Low immunologic
risk
Creeping Creatinine Study (22), 2ASCERTAIN: Assessment of Everolimus in Addition to Calcineurin

Inhibitor Reduction in the Maintenance of Renal Transplant Recipients (26), 3CONVERT (27),
4
CONCEPT (28), 5STN: Spare-The-Nephron (29), 6post-CONCEPT (30)
*Unfavorable factors of mTOR inhibitor proteinuria > 500 mg/, eGFR 40 mL/
min/1.73 m2
30
5.2
Regimen
Level
Calcineurin inhibitor +
Mycophenolate
Cyclosporine level:
C0: 60-80 ng/mL
C2: 400-600 ng/mL
Tacrolimus level:
C0: 4-5 ng/mL
mycophenolate
CNI
mTOR inhibitor +
Calcineurin inhibitor
Minimization
mTOR inhibitor level:

C0: 5-10 ng/mL
Cyclosporine level:
C0: 30-60 ng/mL
C2: 200-300 ng/mL
Tacrolimus level:
C0: 2-3 ng/mL
mTOR inhibitor +
Mycophenolate
mTOR inhibitor level:

C0: 5-10 ng/mL
31
6. CMV
4 (31-34)
6.1: ATG CMV [1A]
6.1.1: ganciclovir valganciclovir 100
6.1.2: CMV
induction therapy
6.1.3:
CMV (ganciclovir/valganciclovir associated neutropenia)
CMV 1-2
100

6.1.4: oral valganciclovir 100
CMV modified preemptive therapy
intravenous ganciclovir 14-21
CMV 1-2 100 (35)
6.1.5: 6.1.3 6.1.4
CMV viremia oral valganciclovir
CMV replication
tacrolimus, cyclosporine, mycophenolates
32
6.1.6: ATG induction therapy acute rejection therapy ATG

oral valganciclovir

prophylactic therapy
modified preemptive therapy
6.2: CMV [(-) CMV IgG]

CMV IgG (D+/R-) ganciclovir valganciclovir 100
[1A]
6.2.1: CMV
induction therapy
6.2.2:
CMV (ganciclovir/valganciclovir associated neutropenia)
CMV
100
6.3: CMV IgG CMV IgG

(D+/R+, D-/R+) IL-2RA CMV
CMV (1B)
6.3.1: CMV
2 3 6
33
6.4: acute rejection lymphocyte depleting agent, pulse methylprednisolone,

ganciclovir valganciclovir 100
CMV 100 [1A]
6.4.1: rejection
rejection CMV
6.5: CMV

6.6: ganciclovir
6.7: valganciclovir
34
7.
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39
INDEX
Page
A
ABO incompatibility/ABO blood group incompatibility
Acute antibody-mediated Rejection
Acute cellular rejection
Acute rejection
Antibody induction
Anti-CD20 antibody
Anti-proliferative agent
Antithymocyte globulin (ATG)
ATG-Fresenius
Avascular necrosis of bone
Azathioprine
16,19
24,26
23,26
13,15,20,23,25,33,34
17
19,24
20
17
19,25
20
25,29
B
Banff
Basiliximab
Borderline rejection
Bortezomib
23
19
23
24,25
C
Calcineurin inhibitor
Chronic Allograft Injury (CAI)
Chronic Allograft Nephropathy (CAN)
CMV IgG
CMV replication
CMV viremia
Creatinine
Cross matching
Cyclosporine
40
20,21,25,28,29,30,31
28
11,13,28
33
32
32
23,29,30
16
20,22,25,31,32
Page
D
Delayed Graft Function (DGF)
Desensitization
Doppler color flow
Double-filtration plasmapheresis (DFPP)
11,23
18,19
28
19
E
eGFR
Everolimus
Expanded Criteria donor (ECD)
28,29,30
21,22,30
11,16,18
F
First-line
20
G
Ganciclovir
Ganciclovir/valganciclovir associated neutropenia
Glossary
32,33,34
32,33
11
H
Hemolytic Uremic Syndrome (HUS)
High immunologic risk
High Risk (HR)
HLA typing
HLA-DP mismatch
HLA-DQ mismatch
HLA-DR
HLA-DR mismatch
Hour post-dose (C2)
Hour trough (C0)
Human Leukocyte Antigen (HLA)
21
30
11,15,16,18
15,16,17
15,18,29
15,18,29
15,29
15,17,18
22
22
11,15
41
Page
I
Induction Therapy
Interleukin 2 receptor antagonist (IL-2RA)
Interstitial Fibrosis
Intravenous immunoglobulin (IVIg)
13,17,18,19,32,33
11,17
28
11,19
L
Low immunologic risk
Low Risk (LR)
Luminex PRA
Lymphocyte depleting agent
30
11,15
16,18
34
M
Maintenance Therapy
Methylprednisolone
Moderate immunologic risk
Moderate Risk (MR)
Modified preemptive therapy
MPA
mTOR inhibitor
Mycophenolate
31,20,21
19,23,25,34
30
11,15
32,33
21
21,22,25,28,29,30,31
19,20,25,29,30,31,32
N
Negative cross match
16,18
O
Osteoporosis
20
P
Panel Reactive Antibody
Plasma volume
Plasmapheresis (PP)
Positive cross match
42
11,15
25
11,19,41
11,19
Page
Precondition
Prolonged-release
Prophylactic therapy
Proteasome inhibitor
Proteinuria
18,19
20,22
33
24
30
R
Recurrent/severe acute cellular rejection
Regimens
Rejection
Rituximab
23
21
14,22,29,34
19,24,25
S
Sirolimus
Specific antibody
Steroid
Subclinical
21,22
16,18
20,23,24
23
T
Tacrolimus
T-cell mediated acute cellular rejection
Thymoglobulin
Tubular Atrophy
19,20,22,25,31,32
23
19,25
28
U
Ultrasonography
28
V
Valganciclovir
Very High Risk (VHR)
Very Low Risk (VLR)
32,33,34
11,16
11,15
Z
Zero mismatch (0-MM)
15,17
43
THAI TRANSPLANT CARE (TTC) KIDNEY
1 2557
500
:
:
4 2
10310
0-2716-6181, 0-2716-6184, 0-2716-6661 4001
0-2716-6183
E-mail: webmaster@transplantthai.org
Website: www.transplantthai.org
3/3 49
10110
. 02-258-7954
02-258-7954

Thai Transplant Care (TTC) Kidney

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Thai Transplant Care (TTC) Kidney

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THAI TRANSPLANT CARE (TTC)

Thai Transplantation Society

TTC: Kidney (September, 2014)

TTC: Kidney (September, 2014)

TTC: Kidney (September, 2014)