The Value of Zero-Hour Implantation Biopsies Volker Nickeleit Nephropathology Laboratory, Department...
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Transcript of The Value of Zero-Hour Implantation Biopsies Volker Nickeleit Nephropathology Laboratory, Department...
The Value of Zero-Hour Implantation Biopsies
Volker Nickeleit
Nephropathology Laboratory, Department of Pathology
The University of North Carolina, Chapel Hill, USA
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
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
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
a) Donor harvest biopsies
b) Implantation protocol biopsies
- 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
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
Baseline Renal Allograft Biopsies
Purpose: a) Diagnosis of (living) donor
disease
b) Identifying “baseline” histological changes
c) Prediction of function / management
Baseline Renal Allograft Biopsies
Purpose: a) Diagnosis of (living) donor
disease
b) Identifying “baseline” histological changes
c) Prediction of function / management
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
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
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)
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
Baseline Renal Allograft Biopsies
Purpose: a) Diagnosis of (living) donor disease
b) Identifying “baseline” histological changes
c) Prediction of function / management
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
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
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
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
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
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
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)
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
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
Chronic vascular rejection – versus - pre-existing donor disease
Chronic inactive vascular rejection Zero-Hour Biopsy: Intimal sclerosis
Pre-existing donor disease and superimposed vascular rejection:12 days post transplantation
Media
Donor disease: intimal sclerosis
Banff type II rejection: Endothelialitis
Pre-existing donor disease and superimposed rejection5 months post transplantation:
Arterial intimal sclerosis and chronic active vascular rejection
Calcineurin-inhibitor induced arteriolopathy -versus –
pre-existing arteriolosclerosis
Cyclosporine arteriolopathy Zero-Hour Biopsy: arteriolosclerosis
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
Back to the Basics of the “Banff Idea”….
…..Bean Counting.
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