Preimplantation analysis of kidney biopsies from expanded

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Transcript Preimplantation analysis of kidney biopsies from expanded

Preimplantation analysis
of kidney biopsies from
expanded criteria donors
Amaia Sagasta, Ana Sánchez-Escuredo,
Frederic Oppenheimer, Manel Solé
Department of Pathology and Kidney Transplant Unit,
Hospital Clínic, Barcelona, Spain
* DISCLOSURE OF INTEREST: The authors report no conflicts of interest.
Introduction I
• Patients with end-stage renal disease attain longer life
expectancy and better quality of life through kidney
transplantation
• Critical shortage of kidneys for transplantation
> 60 y
45-60 y
30-45 y
15-30 y
< 15 y
ONT 2011
Introduction II
ECD group definition
Efforts to expand the kidney donor pool
Incorporation of expanded criteria donors (ECD)
Age ≥ 60 years
OR
Age 50-59 years with ≥ 2 risk factors :
• Death by cerebrovascular accident
• History of hypertension
• Creatinine level > 1.5 mg/dL
Introduction III
ECD group associated problems
Suboptimal post-transplant function
Careful selection of the
Shorter graft survival
Preimplantation kidney
grafts before trasplantation
biopsy in ECD
USA (ECD) *
Spain (>60y) #
Implanted
Discarded
(total)
Discarded
(due to bx)
59%
41%
51%
67.5%
32.5%
41.5%
*Sung RS, et al. Transplantation. 2005 May 15;79(9):1257-61
#ONT
2011
Introduction IV
IB practice and interpretation
• Scores in use:
– Remuzzi score (Rs):
• Glomerular global esclerosis (GS), tubular
atrophy (TA), interstitial fibrosis (IF),
arterial and arteriolar narrowing (CV)
– Banff score based modifications:
Interobserver
variability
• Arteriolar hyalinosis (AH), mononuclear cell
interstitial inflammation (ii)
• Techniques in use:
– Frozen sections, Paraffin sections
Lack of universally accepted practice guidelines for biopsy
processing and interpretation of the histological findings
Aim of the study
1. To analyze the correlation between:
a. Different observers, using frozen sections
b. Different techniques: paraffin vs. frozen (same observer)
2. To analyze if the modification of the score
parameters could improve the correlation:
a. Analysis of an alternative score (As)
i.
Alternative GS parameter
ii.
Combined tubulo-interstitial parameter
iii.
AH parameter
Materials and Methods I
Study design
Original report
• Pathologist-on-call: Several
general pathologists
• Time of transplantation
• Frozen section
Materials and Methods II
Scoring of biopsies
GS:
Rs
0= none
1= <20%
2= 20-50%
3= > 50%
As
0= none
1= 1-10%
2= 11-20%
3= > 21%
TA:
0= absent
1= ≤ 25%
2= 26-50%
3= > 50%.
CV:
0= absent
1= ≤ 25%
2= 26-50%
3= > 50%.
IF:
0= ≤ 5%
1= 6-25%
2= 26-50%
3= > 50%.
AH:
0= absent
1= mild to moderate in
at least one
2= moderate to severe
in >1
3= severe in many
Materials and Methods III
Elegibility; statistics
• Elegibility for transplant or discard (biopsy):
– ≤ 4 points Remuzzi score: acceptance / >4 : discard
• Statistics for concordance in organ elegibility analysis:
– Kappa index (K): values between 0 (no agreement) and 1 (perfect
agreement)
• Statistics for correlation analysis (parameters, scores):
– Kendall’s Tau b (KTb): values between -1 (perfect disagreement)
and 1 (perfect agreement), 0 (absence of association)
Results I - Parameters
Interobserver
correlation
(frozen sections)
correlation between techniques:
PS/FS
(same observer)
Kendall’sTau b
Lower C.I.,KTb
Upper C.I.,KTb
Kendall’s Taub
Lower C.I.,KTb
Upper C.I.,KTb
GS (Rs)
0.19
-0.06
0.45
0.36
0.13
0.59
GS (As)
-
-
-
0.30
0.11
0.50
TA
0.10
-0.09
0.30
0.16
-0.13
0.45
IF
0.24
0.03
0.44
0.35
0.15
0.55
TA/IF (As)
-
-
-
0.16
-0.13
0.45
CV
0.21
0.005
0.41
0.31
0.11
0.51
AH (As)
-
-
-
0.32
0.18
0.46
PS: parraffin sections (PAS); FS: frozen sections (H/E)
Results II - Scores
Interobserver
correlation
(frozen sections)
Remuzzi score
correlation between techniques:
PS/FS
(same observer)
Kendall’s
Tau b
Lower C.I.,
KTb
Upper C.I.,
KTb
Kendall’s
Taub
Lower C.I.,
KTb
Upper C.I.,
KTb
0.10
-0.09
0.30
0.31
0.15
0.47
0.29
0.12
0.47
Alternative sc.
PS: parraffin sections (PAS); FS: frozen sections (H/E)
Results III
Concordance in organ acceptance
Kappa value
(95% CI)
Interobserver
concordance
(frozen sections)
concordance between techniques:
PS/FS
(same observer)
0.33
0.35
(0.05-0.61)
(0.11-0.59)
PS: parraffin sections (PAS); FS: frozen sections (H/E); ORFS: original report frozen section (H/E)
Importance of observed differences in organ acceptance:
• FS revision a posteriori by single observer would have
resulted in 9.75% more discard than ORFS
• FS revision would have resulted in 7.6% more discard than
PS revision by the same observer
Conclusions
• The evaluation of the score items by a single, trained
observer improved the correlation in all values, despite
the use of different techniques
• Remuzzi score was the parameter with the best
improvement in correlation
• Given the relevance of the observed differences in organ
acceptance, specific training is advisable irrespective
of the technique used
Thank you for your attention
[email protected]
References
•
Remuzzi G, Grinyo J, Ruggenenti P et al. Early experience with dual kidney transplantation in adults using
expanded donor criteria. Double Kidney Transplant Group (DKG). J. Am. Soc.Nephrol. 1999; 10; 2591–2598.
•
Perico N, Ruggenenti P, Scalamogna M, Remuzzi G.Tackling the shortage of donor kidneys: how to use the best
that we have. Am.J.Nephrol.2003;23:245-259.
•
Munivenkatappa RB, Schweitzer EJ, Papadimitriou JC et al. The Maryland aggregate pathology index: a deceased
donor kidney biopsy scoring system for predicting graft failure. Am. J.Transplant. 2008; 8; 2316–2324.
•
El-Husseini A, Sabry A, Zahran A et al.Can Donor implantation renal biopsy predict long-term renal allograft
outcome?Am.J.Nephrol.2007;27:144-151
•
Snoeijs MG, Boonstra LA, Buurman WA et al.Histological assessment of pre-transplant kidney biopsies is
reproducible and representative. Histopathology 2010;56;198-202.
•
Sung RS, Christensen LL, Leichtman AB et al.Determinatns of discard of expanded criteria donor kidneys: impact
of biopsy and machine perfusion. Am.J.Transplant.2008;8:738-792.
•
Furness PN, Taub N, Assmann KJ et al. International variation in histologic grading is large, and persistent
feedback does not improve reproducibility. Am. J. Surg. Pathol. 2003; 27; 805–810.
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Organización Nacional de Transplantes (ONT) Database