PowerPoint-Pr

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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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• Donor harvest biopsies
• Harvest biopsies of limited practical
  valuePurpose 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
valuePurpose 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
n175 kidney transplantsn114 post perfusion
zero-hour biopsies (65 of all
organs)n1 Complication (extended
bleeding) 0.9 of all biopsiesBiopsy
procedure biopsy gun, 15 gauge needle, 1
or 2 coresTissue 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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N114 biopsies n72 cadaveric, n42 living
origin donor age median 37 yrs (range
9 61 yrs)N78 (68) Banff minimal
adequacy (gt 6 glomeruli and gt 1
artery caveat often medulla)N22 (20)
Normal (no arteriosclerosis, no
glomerulosclerosis)N42 (37)
Immunofluorescence analysis N0
Immuncomplex mediated GN N0 C4d
positivity N0 Tubular HLA-DR
expressionN0 (0) Active disease

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Histological features (total n114)
Glomeruli median 14 (range 0 -
52)Sclerosed Glomeruli gt 3 sclerosed
glomeruli n1 Interst. fibrosis 0
n66, lt10 n31, gt 10 n13 Tub.
Atrophy 0 n84, lt 10 n22, gt
10 n6Arteriolosclerosis (0-4) (0)
n57, (1) n33, (2) n10, (3) n1
Intimal sclerosis (0-4) (0) n45,
(1) n24, (2) n17, (3) n4 ATN
(0-4) (0) n0, (1) n78, (2)
n48, (3) n14, (4) n1
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Moderate Arteriosclerosis ( Scoring gt 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 Arteri
osclerosis 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 atrophy arteriolosclero
sis (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 lossDemographic
data Recipient age, sex, race, number of
tx Donor age, sex, race Type of donor
organ
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Statistical analysisHistological features -
globally sclerotic glomeruli -
interstitial fibrosis - tubular
atrophy - arteriolosclerosis -
arterial intimal sclerosis Significantly
correlated to one anotherLeading variable
arterial intimal sclerosis
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Statistical analysis Arterial intimal
sclerosisA) 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 plt 0.0001B)
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 n31 13
1.27 .32 1.25 .33
1 n14 14
1.28 .46 1.29 .39
2 n7 0
1.60 .43 1.62 .40 3 n2
0 1.25 .07 1.35 .21
ns ns ns ns
plt0.04 ns ns ns ns mild
(0-1) n45 13 1.27
.36 1.26 .34
moderate (2-3) n9
0 1.52 .40 1.55 .37
ns ns ns plt0,04
plt0.02 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 ATNA) 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 1 plt0.001B)
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 n7
1.13 0.29 1
n16 1.66
.79 2 n27
1.82 1.31
(3 and 4) n6 2.17 1.35
ns plt0.05
ns ns ns ns
Evaluation of functioning renal grafts
without rejection during 12 months (total n54)
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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
Zero-Hour Biopsy Intimal sclerosis
Chronic inactive vascular rejection
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Pre-existing donor disease and superimposed
vascular rejection 12 days post transplantation
Banff type II rejection Endothelialitis
Donor disease intimal sclerosis
Media
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Pre-existing donor disease and superimposed
rejection 5 months post transplantation
Arterial intimal sclerosis and chronic active
vascular rejection
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• Calcineurin-inhibitor induced arteriolopathy
• versus
• pre-existing arteriolosclerosis

Zero-Hour Biopsy arteriolosclerosis
Cyclosporine arteriolopathy
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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 Disease1)
Strongly recommend adequate baseline implantation
biopsies2) 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