the value of zero-hour implantation biopsies volker nickeleit nephropathology laboratory, department...
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![Page 1: The Value of Zero-Hour Implantation Biopsies Volker Nickeleit Nephropathology Laboratory, Department of Pathology The University of North Carolina, Chapel](https://reader036.vdocument.in/reader036/viewer/2022062713/56649cc45503460f9498df3a/html5/thumbnails/1.jpg)
The Value of Zero-Hour Implantation Biopsies
Volker Nickeleit
Nephropathology Laboratory, Department of Pathology
The University of North Carolina, Chapel Hill, USA
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Baseline Renal Allograft Biopsies
Purpose:
1) Organ adequacy (Harvest biopsy)
2) Pre-existing Disease (Protocol Biopsy)
a) Post transplant biopsy interpretation (“book-keeping”)
b) Prediction of function / management
c) Diagnosis of (living) donor disease
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a)Donor harvest biopsies
Harvest biopsies of limited practical value
Purpose: 1) Organ adequacy :+ / - (adjunct tool)
2) Pre-existing Disease : + / -
a) Adequate post transplant biopsy interpretation
b) Implantation protocol biopsies
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Harvest biopsies of limited practical value
Purpose: 1) Organ adequacy : + / - (adjunct tool)
2) Pre-existing Disease : + / - a) Adequate post transplant biopsy
interpretation (“book-keeping”)
Improvement: a) standardization of technique, i.e. needle cores,
deep wedges
b) complete tissue evaluation (PAS, trichrome) and material sharing with managing transplant center
c) systematic studies of criteria to discard organs
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a) Donor harvest biopsies
b) Implantation protocol biopsies
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- Implantation protocol biopsies to assess donor disease
- Strengths:a) full histological evaluation “no time
constraints”b) good assessment of lesions “special stains”
- Problems:a) Risk of complications / bleeding (caveat: living donations)
b) Sampling: 15 gauge needles, only one core, no frozen tissue, subcapsular wedge biopsies
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UNC experience with post perfusion biopsies n=175 kidney transplants
n=114 post perfusion zero-hour biopsies (65% of all organs)
n=1 Complication (extended bleeding)0.9% of all biopsies
Biopsy procedure: biopsy gun, 15 gauge needle, 1 or 2 cores
Tissue fixation in formalin and fresh frozen collection
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Baseline Renal Allograft Biopsies
Purpose: a) Diagnosis of (living) donor
disease
b) Identifying “baseline” histological changes
c) Prediction of function / management
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Baseline Renal Allograft Biopsies
Purpose: a) Diagnosis of (living) donor
disease
b) Identifying “baseline” histological changes
c) Prediction of function / management
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N=114 biopsies n=72 cadaveric, n=42 living origin donor age: median 37 yrs (range: 9 – 61
yrs)
N=78 (68%) Banff minimal adequacy (> 6 glomeruli and > 1 artery; caveat: often
medulla)
N=22 (20%) Normal (no arteriosclerosis, no
glomerulosclerosis)
N=42 (37%) Immunofluorescence analysis N=0 Immuncomplex mediated GN N=0 C4d positivity N=0 Tubular HLA-DR expression
N=0 (0%) Active disease
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Histological features (total n=114):
Glomeruli median: 14 (range: 0 - 52)
Sclerosed Glomeruli > 3 sclerosed glomeruli n=1
% Interst. fibrosis 0% n=66, <10% n=31, > 10% n=13
% Tub. Atrophy 0% n=84, < 10% n=22, > 10% n=6
Arteriolosclerosis (0-4) (0) n=57, (1) n=33, (2) n=10, (3) n=1
Intimal sclerosis (0-4) (0) n=45, (1) n=24, (2) n=17, (3) n=4
ATN (0-4) (0) n=0, (1) n=78, (2) n=48, (3) n=14, (4) n=1
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Moderate Arteriosclerosis ( Scoring: > 2 / 4 )
21 / 114 biopsies (18%)
18% of cadaveric organs
N= 13 cadaveric organs (mean: 37 yrs, range: 18 –
59 yrs)
N= 1 secondary FSGS (cadaveric organ)
19% of organs from living donations
N= 8 organs of living origin (mean: 46 yrs, range: 37-
54 yrs)
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Baseline Renal Allograft Biopsies
Purpose: a) Diagnosis of (living) donor
disease
Unexpected arteriosclerosis (suggestive of hypertension induced damage) in 19% of donors
b) Identifying “baseline” histological changes
Arteriosclerosis and arteriolosclerosis in 40% of organs
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Baseline Renal Allograft Biopsies
Purpose: a) Diagnosis of (living) donor disease
b) Identifying “baseline” histological changes
c) Prediction of function / management
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Acute rejection - graft failure( 12 months post transplantation)
Multi-organ recipients 4/ 114 (4%)
Acute rejection 19/ 110 (17%)
Graft failure 5/ 110 (5%)
BK-Virus nephropathy 8/ 110 (8%)
Lost for follow up 4/ 114 (4%)
40 Patients excluded from functional analyses
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Statistical analysisHistological features: % globally sclerotic glomeruli
% interstitial fibrosis% tubular atrophyarteriolosclerosis (0-4)arterial intimal sclerosis (0-4)ATN (0-4)
Clinical data (during 12 months post transplantation):S-Creatinine: 2 weeks, 1, 3, 6, 12 months post txDelayed graft function: at least 1 episode of HD post txBlood-Pressure: 3, 6, 12 months post txAcute rejection episodesGraft loss
Demographic data: Recipient age, sex, race, number of tx
Donor age, sex, raceType of donor organ
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Statistical analysis
Histological features: - % globally sclerotic glomeruli
- % interstitial fibrosis- % tubular atrophy- arteriolosclerosis - arterial intimal sclerosis
Significantly correlated to one another
Leading variable: arterial intimal sclerosis
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Statistical analysis: Arterial intimal sclerosis
A) Arterial intimal fibrosis is correlated with the age of the donor
Age in years( mean + SD)
Scoring 0 27,9 + 12.0
Scoring 1 42,7 + 8.3
Scoring 2 44.7 + 11.9
Scoring 3 46,7 + 6.3 p< 0.0001
B) Arterial intimal fibrosis is not correlated with donor organ type, donor sex, donor race
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Statistical analysis **: Arterial intimal sclerosis Arterial intimal sclerosis * Delay. S-Creatinine (mean + SD) Blood pressure
( scoring 0-3 ) Funct. 2 1 3 6 12 3 6 12
% Wks m m m m m m mths
0 n=31 13% 1.27 + .32 1.25 + .33
1 n=14 14% 1.28 + .46 1.29 + .39
2 n=7 0% 1.60 + .43 1.62 + .40
3 n=2 0% 1.25 + .07 1.35 + .21
ns ns ns ns p<0.04 ns ns ns ns
mild (0-1) n=45 13% 1.27 + .36 1.26 + .34
moderate (2-3) n=9 0% 1.52 + .40 1.55 + .37
ns ns ns p<0,04 p<0.02 ns ns ns ns * Biopsies fulfilling minimal adequacy criteria only ** Evaluation of functioning renal grafts without rejection during 12 months
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Statistical analysis: ATN
A) Acute tubular injury (ATN) is correlated with donor organ type
Cadaveric Living donation
Scoring 0 4 9
Scoring 1 14 18
Scoring 2 38 10
Scoring 3 11 3
Scoring 4 0 1p<0.001
B) Acute tubular injury (ATN) is not correlated with delayed graft function, acute rejection episodes, arterial hypertension
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Statistical analysis **: ATN
Acute tub. injury Delay. Function S-Creatinine (mean + SD)
( scoring 0 - 4 ) 2 1 3 6 12
Wks m m m m
0 n=7 1.13 + 0.29
1 n=16 1.66 + .79
2 n=27 1.82 + 1.31
(3 and 4) n=6 2.17 + 1.35
ns p<0.05 ns ns ns ns
** Evaluation of functioning renal grafts without rejection during 12 months (total n=54)
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Baseline Renal Allograft Biopsies
Purpose: c) Prediction of function / management
Arterial intimal sclerosis: - associated with increased S-Cr 3 and 6 months post
tx
- associated with donor age
ATN: - associated with increased S-Cr 2 weeks post tx
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Baseline Renal Allograft Biopsies
Purpose: a) Diagnosis of (living) donor disease
b) Identifying “baseline” histological changes
Impact on diagnoses in post transplant allograft
biopsies
c) Prediction of function / management
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Chronic vascular rejection – versus - pre-existing donor disease
Chronic inactive vascular rejection Zero-Hour Biopsy: Intimal sclerosis
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Pre-existing donor disease and superimposed vascular rejection:12 days post transplantation
Media
Donor disease: intimal sclerosis
Banff type II rejection: Endothelialitis
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Pre-existing donor disease and superimposed rejection5 months post transplantation:
Arterial intimal sclerosis and chronic active vascular rejection
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Calcineurin-inhibitor induced arteriolopathy -versus –
pre-existing arteriolosclerosis
Cyclosporine arteriolopathy Zero-Hour Biopsy: arteriolosclerosis
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Baseline (Zero-Hour) Biopsies
• Important for adequate classification of transplant pathology
caveat: fibrosis and atrophy may be donor disease! active and scarred rejection may be superimposed on
donor disease!
• Prediction on graft function
• Some help to detect (living) donor disease
• Help for scientific projects (e.g. gene expression analysis post tx, latent viral load measurements etc)
Specific diagnoses
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Back to the Basics of the “Banff Idea”….
…..Bean Counting.
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Banff “Edition” for reporting Donor Disease
1) Strongly recommend adequate baseline implantation biopsies
2) Separately score and report donor disease (“D”)
Dcv (0-3): arterial intimal fibroelastosis with marked
multilayering of elastic lamellae
Dah (0-3), Dci (0-3), Dct (0-3)
Dcg: percentage of globally sclerotic glomeruli
3) Post transplantation: - score Banff lesions as usual - specifically comment on previous “D” scores