Preimplantation analysis of kidney biopsies from

expanded criteria donorsAmaia 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

ONT 2011

> 60 y

45-60 y

30-45 y

15-30 y

< 15 y

Introduction IIECD 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 IIIECD group associated problems

#ONT 2011

Implanted Discarded (total)

Discarded (due to bx)

USA (ECD) * 59% 41% 51%

Spain (>60y) # 67.5% 32.5% 41.5%

*Sung RS, et al. Transplantation. 2005 May 15;79(9):1257-61

Suboptimal post-transplant function

Shorter graft survival Careful selection of the

grafts before

trasplantation

Preimplantation kidney

biopsy in ECD

Introduction IVIB 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:• Arteriolar hyalinosis (AH), mononuclear

cell interstitial inflammation (ii)

• Techniques in use: – Frozen sections, Paraffin sections

Interobserver variability

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:

1. Analysis of an alternative score (As)

1. Alternative GS parameter

2. Combined tubulo-interstitial parameter

3. 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 As 0= none 0= none1= <20% 1= 1-10%2= 20-50% 2= 11-20%3= > 50% 3= > 21%

TA:0= absent1= ≤ 25%2= 26-50%3= > 50%.

IF:0= ≤ 5%1= 6-25%2= 26-50%3= > 50%.

CV:0= absent1= ≤ 25%2= 26-50%3= > 50%.

AH: 0= absent1= mild to moderate in at least one2= moderate to severe in >13= severe in many

Materials and Methods IIIElegibility; 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)

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

Remuzzi score 0.10 -0.09 0.30 0.31 0.15 0.47

Alternative sc. 0.29 0.12 0.47

PS: parraffin sections (PAS); FS: frozen sections (H/E)

Results IIIConcordance in organ acceptance

Interobserver

concordance

(frozen sections)

concordance between techniques:

PS/FS

(same observer)

Kappa value(95% CI)

0.33(0.05-0.61)

0.35(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

asagasta@clinic.ub.es

Thank you for your attention

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.

• Organización Nacional de Transplantes (ONT) Database