AN ANALYSIS OF CADAVER DONOR AND KIDNEY BIOPSY PARAMETERS WITH CORRELATION TO TRANSPLANT OUTCOMES Martin Mozes MD, Mel Schwartz MD, Janis Orlowski MD Michael Harmon BSN, Ronald Skolek BSN Regional Organ Bank of Illinois and Rush Presbyterian -St. Lukes Medical center, Chicago IL. ARE WE DISCARDING KIDNEYS APPROPRIATELY ?

Background Proportion of kidneys from cadaveric donors over age 50 (“marginal donors”) has >doubled over 10 years to 30% of total. The kidney discard rate from “marginal” donors is >32%, double that of overall discard rates. Transplant outcomes with these kidneys is acceptable. There is a need to define factors leading to discard There is a need to validate the correctness of the decision to discard “marginal” kidneys.

Age % Increase (%) > (2.4)1,019 (8.8)385% ,294 (14.3)2,468 (21.2)91% ,535 (72.3)7,234 (62.1)10.7% < (11.0)924 (7.9)7.2% Total9,035 (100%)11,645 (100%)29% UNOS 2000 Annual Report Age Increase (%) > (2.4)1,019 (8.8)X ,294 (14.3)2,468 (21.2)X ,535 (72.3)7,234 (62.1) X 1.1 < (11.0)924 (7.9) X 0.9 Total9,035 ( 100%) 11,645 ( 100%) 29% UNOS 2000 Annual Report CADAVER DONOR AGE

Discard Rates after Recovery of Cadaveric Kidneys * Data through November 30,2000 SRTR

Donor Traits Associated with Kidney Graft Failure* Hazard Ratio Hypertensive, High Creatinine Hypertensive, Normal Creatinine Non-Hypertensive, High Creatinine Non- Hypertensive, Normal Creatinine Donor Age (years) * Deaths not due to graft failure were censored SRTR

Survival Benefit from Marginal Kidneys Days since transplantation (Equal time from wait-listing) Relative Risk (RR) of Death SRTR

PURPOSE of THE STUDY *To determine the ROBI kidney discard rates in Marginal Donors. *To determine donor and kidney biopsy factors associated with discard *To design a predictive score for kidney discard. *To validate the decision to discard.

Methods Data reviewed of all ROBI cadaver donors with kidney biopsy at ROBI during Kidney biopsy findings (Wedge-frozen and permanent) reviewed, graded and coded. Kidney recipients identified-with F/U 6M-5 years. Uni and multivariate analyses performed.

DISCARD RATES OF BIOPSIED KIDNEYS 539 DONORS (D) – 957 KIDNEYS (K) DISCARDS K (34%) BILATERAL BIOPSIES 418 D– 836 K DISCARDS – 305 K (36%) UNILATERAL BIOPSIES 121 D – 121K DISCARDS – 27 K (22%) DONORS WITH BIOPSY RELATED DISCARDS 361 D – 772 K DISCARDS: BILAT - 91 D UNILAT- 43 D NONE D ALL DISCARDS: 225 K (31%)

Donor Parameters-Bilateral Biopsies (N=361)* AGE: ( Range 3-82) GENDER: Male- 177(49%)Female- 184 (51%) RACE: C- 233(64.5%), AA- 96(26.6%), H-24(6.6%) O- 8 (2.2%) HTN: 175(48%) TREAT. HTN:136(38%) > 5 yrs. 85(49%) < 5 yrs.- 68 (39%) dur. unknown - 22(12%) DM: 31(8.8%) (IDDM -12, NIDDM -19) P.V.D.: 14 (4%) C.V.D: 24 (6.6%)*Biopsy related discards

DONOR PARAMETERS II (BILATERAL BIOPSIES*) S. CREAT.: ADMIT FINAL: GFR** :ADMIT FINAL PROTEINURIA: 0 -TRACE:60%; 1+:16%; 2+:14%; 3+:8%; 4+:0.6% DIC: 19 (5.3%) INTRA-OP FINDINGS: AORTIC PLAQUE: None-17%; Mild-40%; Mod.-19%;Severe-16% RENAL A. PLAQUE:None-44%; Mild-27%; Mod.-12%; Sev-11% CYSTS: None 80%; 1-2: 16%; >2: 17% ** Cockroft-Gault estimation*Biopsy related discards

Grading of Biopsy Findings 1. Glomerulosclerosis = % sclerotic glomeruli 2. *Atrophic cortical tubules 3. *Cortical Interstitial Fibrosis 4. *Arterial Lumen occluded by sub-intimal fibrosis 5. *Arterial Lumen occluded by sub-intimal hyalinosis *Semi-quantitated in quartiles and graded 1+ to 4+

FROZEN VS. PERMANENT SECTION READINGS COMPARISON BIOPSIES Median (25th, 75th percentiles ) FrozenPermanent # GLOMERULI35 (24, 51)43 (27, 63) # SCLEROTIC GLOMERULI 1 (0, 5)3 (0,8) % ATROPHIC CORT.TUBULES 1 (0, 1)1 (0,1) % INTERSTITIAL FIBROSIS 1 (0,1)1 (0,1) % ARTERIAL LUMEN OCCLUSION SUBINTIMAL FIBROSIS 0 (0,1)0 (0,1) HYALINOSIS 0 (0,1)0 (0,1) coding key : 0 = none, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, 4=76=100%

Donor Factors as Predictors of Kidney Discard Univariate Analysis for “all or some” kidneys transplanted Significant p<.05Not Significant AgeHeight RaceWeight Hx. HTNDonor Date Hx.Rx.HTNLupus Hx HTN> 5 yearsSCD Hx DMProteinuria Duration DMDIC CVD GFR (admit to final) Creat. Final GFR Admit GFR Final

Predictive Model For 2/2 KIDNEY USE (227/361) Age Points Under Race Caucasian 0.0 AA -1.1 Hispanic 0.2 Other -1.8 GFR final < GFR final > Hx. DM 0.0 No Hx HTN 1.6 O-Tr Prot 0.6 O-Mild A.Plaque pts=80% use and 5.6 pts>90% use AUC = 0.831

Predictive Model For 2/2 KIDNEY DISCARD (91/361) VariablePoints Age Under Race Caucasian 0.0 AA 1.1 Hispanic -0.8 Other 1.0 GFR final < GFR final > Hx DM 1.1 Hx Rx HTN 1.2 >4.2 Points.=>80% bilateral discard

Prediction models with Donor and Biopsy Parameters HxRxHTN.39 Creat.Final.53 Age.96 % GlomScl Art. Hyalinosis ODDS RATIOS.

Optimal* Predictive Ability - Donor and Biopsy Parameters *Using splines to fit each variable

Marginal Kidneys - Patient and Graft Survival

Graft Survival for ”Paired to Discard” Kidneys Recipient Characteristics (N=25*) Gender: M-18 F-7 Age: (34-67) DM: Yes-10 No-14 Race: C-13 AA-7 H-4 O-1 CIT: 27+8 hrs. MP- 9 S. Creat at 6 M *25/43 with complete data

summary The Kidney Discard rates in Marginal Donors is>30% Donor factors predictive of discard are age, race, GFR (admit and final),HTN and DM. Predictive Biopsy factors are: % Glomerulosclerosis and degree of Arteriolar hyalinosis. A highly accurate predictive score for kidney discard can be developed based on above factors. Kidneys paired to discarded kidneys result in acceptable outcomes when transplanted.

CONCLUSIONS Current transplant practices result in a high discard rate of “marginal donor” kidneys. Transplantation of kidneys similar to those currently being discarded results in acceptable outcomes. More wide spread application of innovative approaches will result in successful transplantation of many more patient: Two-for-one transplants. Alternate recipient lists for marginal kidneys. Accelerated placement protocols for marginal donors.