1. 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.

2. 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

3. 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

4. Introduction III ECD group associated problems # ONT 2011 ImplantedDiscarded (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

5. 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: 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

6. 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

7. Materials and Methods I Study design

8. Original report Pathologist-on-call: Several general pathologists Time of transplantation Frozen section

9. Materials and Methods II Scoring of biopsies GS: Rs As0= none 1= <20% 1= 1-10% 2= 20-50% 2= 11-20% 3= > 50% 3= > 21% TA: 0= absent 1= ≤ 25% 2= 26-50% 3= > 50%. IF: 0= ≤ 5% 1= 6-25% 2= 26-50% 3= > 50%. CV: 0= absent 1= ≤ 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

10. 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)

11. Results I - Parameters Interobserver correlation (frozen sections) correlation between techniques: PS/FS (same observer) Kendall’sTau bLower C.I.,KTbUpper C.I.,KTbKendall’s TaubLower C.I.,KTbUpper C.I.,KTb GS (Rs)0.19-0.060.45 0.36 0.130.59 GS (As)---0.300.110.50 TA 0.10 -0.090.30 0.16 -0.130.45 IF 0.24 0.030.44 0.35 0.150.55 TA/IF (As)--- 0.16 -0.130.45 CV0.210.0050.410.310.110.51 AH (As)---0.320.180.46 PS: parraffin sections (PAS); FS: frozen sections (H/E)

12. 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 -0.090.30 0.31 0.150.47 Alternative sc. 0.29 0.120.47 PS: parraffin sections (PAS); FS: frozen sections (H/E)

13. Results III Concordance 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

14. 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

15. asagasta@clinic.ub.es Thank you for your attention

16. 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