7-2 transplantation case-based discussion · 7-2 transplantation case-based discussion tadashi...
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7-2 TransplantationCase-Based Discussion
Tadashi Sofue, MD, PhD
Division of Nephrology and Dialysis, Department of Internal Medicine, Kagawa University Hospital
The 58th JSN 2015/6/4@NagoyaAPSN Continuing Medical Education Course 2015
Division of Nephrology and Dialysis, Department of CardioRenal and CerebroVascular Medicine,
Faculty of Medicine.
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Statement of Disclosure
• The author does not have any financial conflict of interest regarding the material in this presentation.
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Patient: 35-year-old MalePast History:Type-2 Diabetes (from 15 years old)
Diabetic retinopathyFamily History:Older sister: DM Mother: DMPresent illness• 15 y.o. Diagnosed with diabetes and hypertension (No treatment)• 25 y.o. Treatment with sulfonylurea • 30 y.o. Kidney dysfunction with nephrotic syndrome• 34 y.o. Initiation of hemodialysis (HD) • 35 y.o. He consulted our hospital for the purpose of a living-donor
kidney transplantation from his father.
Case Presentation
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Status before KT
StatusHeight:165 cm Body weight:72 kg BMI: 26.5Blood pressure: 162/87 mmHg Heart rate:60/minLung: clear, no rale. Heart: regular, no murmurAbdomen: soft and flatLeg edema: none, left forearm: AVF
Patient backgroundOccupational history: sake dealer (drank two cans of beer/day)Smoking history: 20×15 years (stopped smoking before KT)
Medication:Candesartan 8 mg 1 tab/dayAmlodipine 5 mg 2 tab/dayDoxazosin 2 mg 1 tab/dayLansoprazole 15 mg 1 tab/day
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Laboratory Data before KTGGTP 15 U/L
CHE 222 U/L
WBC 5,690 /μL
RBC 386 104/μL
Hb 11.0 g/dL
Ht 34.1 %
Plt 24.0 104/μL
CRP 0.11 mg/dL
TP 7.0 g/dL
Alb 3.7 g/dL
BUN 57.8 mg/dL
Cr 12.84 mg/dL
Na 140 mEq /L
K 5.3 mEq /L
Cl 99 mEq /L
Ca 9.4 mg/dL
IP 7.6 mg/dL
T-bil 0.3 mg/dL
GOT 3 U/L
GPT 9 U/L
ALP 229 U/L
LDH 144 U/L
C3 70 mg/dL
C4 27 mg/dL
CH50 31.6
ANA 40 fold
IgA 218 mg/dL
IgG 1,237 mg/dL
IgM 88 mg/dL
iPTH 152 pg/mL
β2MG 24.7 mg/L
HbA1c (NGSP) 6.7 %
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Examination before KT
• CT: no malignancy• Gastrointestinal endoscopy: n.p.• Colorectal endoscopy: n.p.• HCV-ab, HBV-ag: negative
Left ventricular hypertrophyEjection fraction: 49%,
Wall motion: diffuse, mild hypokinesis
Sinus rhythm
ECGCTR = 44%
Chest Xp
Echo cardiography
Myocardial Ischemia?
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Father (72 years old)• Height: 168 cm Body weight: 72 kg BMI: 25.5• Smoking: 10/day × 50 years• Past history: hypertension• Medication:
Carvedilol 20 mg 1 tab/dayAmlodipine 5 mg 1 tab/ day
• Blood pressure:128/70 mmHg• Kidney function:Cr 0.77 mg/dL eGFR 75.7 mL/min/1.73 m2
• Urinary protein (dipstick): negative• Urinary occult blood (dipstick): negative• Urinary albumin excretion (UAE):16.7 mg/gCr
Donor Examination (1)
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• Gastrointestinal endoscopy: atrophic gastritis• Immunochemical fecal occult blood test: negative• ECG:within normal range• UCG:EF 73%, no asynergy• HCV-ab, HBV-ab: negative
Enhanced 3D-CT
Donor Examination (2)
99mTc-MAG3 scintigraphy
Split kidney function: right/left=48/52 No abnormality of renal artery or vein
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Immunological Condition Histocompatibility test
CDC XM : T(−) Bw (−) Bc (−)Flow XM : T(−) B(−)Flow PRA : class I (+) class II (−)HLA mismatch: 3/6
Blood-type Incompatible (B+ → O+) Recipient anti-B IgG 64-foldRecipient anti-B IgM 64-fold
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Type-2 diabetes Possibility of myocardial ischemia Marginal donor with hypertension ABO-incompatible KT
Problems Associated with this Case
Indication or contraindication for LDKT?
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Sørensen VR, et al. Diabetologia 2007;50(5):922-9
KT for diabetic patients markedly improves survival rates.
Transplantation for Diabetic Patients
Transplant with diabetes
Waiting list with diabetes
Non-candidates with diabetes
Factors aggravating BS control• CNI • PSL• Weight gain
Diabetic patients are not contraindicated for KT
Diabetic patients with ESRD
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Although a positive myocardial perfusion study is predictive of CAD (more than 70%), a poor negative predicted value (64.6%) was reported in cases of ESRD with DM.
Negative
Myocardial perfusion scintigraphy (Recipient)
Possibility of Myocardial Ischemia (1)
Welsh RC, et al. Transplantation 2011;91(2):213-8
Myocardial perfusion imaging and degree of coronary artery stenosis
CAD>70%
Negative
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CAG
Wall motion: intact, EF 68%
LVG
Possibility of Myocardial Ischemia (2)
Overall, he showed a low risk of cardiovascular events in the peri-operative period.
No apparent stenosis was observed in his coronary artery.
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To prevent acute antibody-mediated rejection caused by anti-blood-type antigen, we treat recipients before ABO-incompatibleKT by antibody removal therapy (plasma exchange and double-filtration plasmapheresis) and inhibition of antibody production.
Plasmapheresis for ABO-incompatible KT
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Age > 70 years oldeGFR <80 (>70) mL/min
HypertensionTwo anti-hypertensive drugs
UAE<30 mg/gCr
Marginal Donor (living-kT)
Acceptable as a living-donor?
This donor candidate had many marginal factors
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Living-donor Criteria in the World and Japan
Amsterdam forum Marginal criteria in JapanAge ≦65 ≦80Kidney function(mL/min/1.73 m2) eGFR≧80 eGFR≧70
BMI ≦35 kg/m2 ≦32 kg/m2
Hypertension ≦140/80 mmHgwith less than 1 drug(age>50, UAE≦30 )
≦140/80 mmHg with no drugor ≦130/80 mmHg
with less than 2 drugs + UAE≦30 mg/gCr
Proteinuria ≦300 mg/day ≦150 mg/day or UAE≦30 mg/gCrDiabetes Excluded HbA1c≦6.5% + UAE≦30 mg/gCr
Amsterdam Forum; Delmonico F, Transplantation. 2005;79(6 Suppl):S53-66Donor criteria for living-donor kidney transplantation in Japan 2014
Age: 72 years oldeGFR: 76 mL/min/1.73 m2
HypertensionTwo anti-hypertensive drugs
UAE: 17 mg/gCr
Acceptable as living marginal donor
Our donor candidate
Pre-transplant lifestyle modifying is also important
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Hypertension and the degree of albuminuria did not affect thedonor kidney function after donation.
Recipients of hypertensive donors with high-normal albuminuriashowed lower eGFR than other recipients.
Living-donor KT from Hypertensive Donors with High-normal Albuminuria (15-30 mg/gCr)
Sofue T, et al. Transplantation 2014; 97(1):104-110
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YES(in Japan)
Problems before KT
Type-2 diabetes Suspected myocardial ischemia ABO incompatible Marginal donor (Hypertension, eGFR)
Indication for LDKT?
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Kidn
ey T
rans
plan
tatio
n
Day -7 Day 7
Clinical Course (1)S-
Cr (m
g/dL
)
10
Basiliximab
TxDay -5 Day 14
5
Prolonged-release Tacrolimus: Trough 8-10 ng/mLMMF (mg) 1,000 2,000 1,500
500250
125
80 40 20mPSL (mg)
HDHDHDHD
Day -2
PEDFPPDFPPRituximab 200 mg
×64
×32
×16 ×16
×8
×4Anti-B IgG titer
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Donor Nephrectomy
Laparoscopy with hand assist
Left kidney
Urologist
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Recipient Operation
Donor renal artery
Recipient internal iliac artery
Donor renal vein
Recipient common iliac vein
First-catch urine
Donor ureter
Donor kidneyAfter perfusion
Preimplantation (0 h) biopsy
at bench
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1.30
Kidn
ey T
rans
plan
tatio
n
Day -7 Day 7
Clinical Course (2)S-
Cr (m
g/dL
)
10
Basiliximab
TxDay -5 Day 14
5
Prolonged-release Tacrolimus: Trough 8-10 ng/mLMMF (㎎) 1,000 2,000 1,500
500250
125
80 40 20mPSL (mg)
HDHDHDHD
Day -2
PEDFPPDFPPRituximab 200 mg
×64
×32
×16 ×16
×8
×4
×4
×8
×16
Anti-B IgG titer
no acute antibody-mediated allograft rejection was observed
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C3
Pathological diagnosis:Fibrous intimal thickening
Global glomerular sclerosis 4/20No IgA deposition
Preimplantation Allograft Biopsy
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3 years
Clinical Course (3)
1 year
1,000 mg
mPSL 2 mg
MMF 1,500 mg
S-Cr
(mg/
dL)
1
2
1 month
Recipient
UP (−) (−) (++)
3 years6 months
S-Cr
(mg/
dL)
1
2
pre
Dona
tion
Donor
1 year
2 years
(+)
2 years
0.77
1.21
1.151.151.10 1.12
6 months
1.301.18
1.41
1.28 1.18
(−)
HbA1c (%)
7.57.8
7.37.0 7.0
OB (−) (−) (+)(−) (++)
UP (−) (−) (−)(−)(−)(−)
4 mg
Prolonged-release Tacrolimus: Trough (ng/mL) 4~6
Lifestyle modifying (stop smoking, reduce Na intake)
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Episode Allograft Biopsy
Indication for episode allograft biopsy• 30% increase in Cr from baseline• Urinary protein > 0.5 g/gCr• Appearance of occult blood in the urine
Possible causes of urinary abnormality in this case Chronic antibody-mediated rejection CNI toxicity Recurrent diabetic nephropathy De novo (or unknown-origin) glomerulonephritis
KDIGO Transplant Work Group, Am J Transplant. 2009; 9 Suppl 3: S33-37.
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Causes of Proteinuria after KT
Modified from Sun Q, et al. PLoS One. 2012;7(5):e36654
n=98, from China
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Banff score:t0,i1,g0,v0,ci2,ct2,cg0,cv0,ah3,aah1,mm3,ptc0No acute rejection, severe IF/TA Arteriolar hyaline thickening (due to diabetes?)No CNI toxicity
Results of Allograft Biopsy (1)
AUC study: Tac-ER AUC0-24 94.2 ng h/mL
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Results of Allograft Biopsy (2)
Post-transplant IgA nephropathyMesangial expansion + IgA deposition in the mesangial domainwith tuft necrosis (no crescent formation)We could not diagnose de novo or recurrent IgA nephropathy, because he did not undergo kidney biopsy before KT.
How can we treat this case?
IgA
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Kawamura T, et al. Nephrol Dial Transplant. 2014;29(8):1546-53
Tonsillectomy with steroid pulse therapy reduced proteinuria in cases of IgA nephropathy involving the native kidney.
Treatment for IgA Nephropathy in Native Kidney
From Japan
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Treatment for Recurrent IgA Nephropathy
Tonsillectomy alone, without steroid pulse therapy, reducedproteinuria in patients with recurrent IgA nephropathy.
An effect of ARB on the improvement of graft survival wasnot evident.
Modified from Kennoki T, et al. Transplantation. 2009;88:935-941 Courtney AE, et al. Nephrol Dial Transplant. 2006;21(12):3550-4.
NS
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Insulin
3 years
Clinical Course (4)
1 year
1,000 mgProlonged-release Tacrolimus: Trough (ng/mL) 4~6
mPSL 2 mg
MMF 1,500 mg
S-Cr
(mg/
dL)
1
2
1 month
Recipient
UP (−) (−) (++)2 years
(+)
6 months
1.301.18
1.41
1.28 1.18
(−)
HbA1c (%)
7.57.8
7.37.0 7.0
OB (−) (−) (+)(−) (++)
7.8Rb
(+)(+)
1.35
Tonsillectomy
4 mg PSL 20 mgmPSL 1,000 mg
Tonsillectomy + steroid pulse therapy reduced urinary abnormality, although his blood glucose was aggravated.
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Summary
Our case shows that:Diabetes, ABO incompatibility, and marginal donor are
not contraindications for living-donor kidney transplantation.
Allograft biopsy is needed to diagnose the causes ofpost-transplant urinary abnormality.
Participation of a nephrologist is needed to prolonggraft survival.