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AN ANALYSIS OF CADAVER DONOR AND KIDNEY BIOPSY PARAMETERS WITH CORRELATION TO TRANSPLANT OUTCOMES

This study analyzes the parameters of cadaveric donor kidneys and kidney biopsies to understand the correlation with transplant outcomes. It aims to determine factors leading to kidney discard and validate the decision to discard "marginal" kidneys.

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AN ANALYSIS OF CADAVER DONOR AND KIDNEY BIOPSY PARAMETERS WITH CORRELATION TO TRANSPLANT OUTCOMES

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  1. ARE WE DISCARDING KIDNEYS APPROPRIATELY ? 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.

  2. Chicago

  3. 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.

  4. CADAVER DONOR AGE Age 1990-1991 1998-1999 % Increase Age 1990-1991 1998-1999 Increase (%) (%) (%) (%) > 65 210 (2.4) 1,019 (8.8) 385% > 65 210 (2.4) 1,019 (8.8) X 4.8 50-64 1,294 (14.3) 2,468 (21.2) 91% 50-64 1,294 (14.3) 2,468 (21.2) X 1.9 11-49 6,535 (72.3) 7,234 (62.1) 10.7% 11-49 6,535 (72.3) 7,234 (62.1) X 1.1 < 10 996 (11.0) 924 (7.9) 7.2% < 10 996 (11.0) 924 (7.9) X 0.9 Total 9,035 (100%) 11,645 (100%) 29% Total 9,035 (100%) 11,645 (100%) 29% UNOS 2000 Annual Report UNOS 2000 Annual Report

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

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

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

  8. 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.

  9. Methods • Data reviewed of all ROBI cadaver donors with kidney biopsy at ROBI during 1996-1999. • 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.

  10. DISCARD RATES OF BIOPSIED KIDNEYS 539 DONORS (D) – 957 KIDNEYS (K) DISCARDS - 332 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 - 227 D ALL DISCARDS: 225 K (31%)

  11. Donor Parameters-Bilateral Biopsies (N=361)* AGE: 51.0 + 15.6 ( 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

  12. DONOR PARAMETERS II (BILATERAL BIOPSIES*) S. CREAT.: ADMIT 1.1 + .4 FINAL: 1.4+ 0.7 GFR** : ADMIT 89.6 + 46.9 FINAL 76.2 + 53.3 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

  13. 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+

  14. FROZEN VS. PERMANENT SECTION READINGS COMPARISON USING @804 BIOPSIES Median (25th, 75th percentiles ) Frozen Permanent # GLOMERULI 35 (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%

  15. Donor Factors as Predictors of Kidney Discard Univariate Analysis for “all or some” kidneys transplanted Significant p<.05 Not Significant Age Height Race Weight Hx. HTN Donor Date Hx.Rx.HTN Lupus Hx HTN> 5 years SCD Hx DM Proteinuria Duration DM DIC CVD GFR (admit to final) Creat. Final GFR Admit GFR Final

  16. Predictive Model For 2/2 KIDNEY USE (227/361) Age Points Under 40 1.5 40-49 1.5 50-59 1.3 60 + 0.0 Race Caucasian 0.0 AA -1.1 Hispanic 0.2 Other -1.8 GFR final < 50 0.0 GFR final > 50 1.4 Hx. DM 0.0 No Hx HTN 1.6 O-Tr Prot 0.6 O-Mild A.Plaque. 0.7 AUC = 0.831 4.2 pts=80% use and 5.6 pts>90% use

  17. Predictive Model For 2/2 KIDNEY DISCARD (91/361) VariablePoints Age Under 40 0.0 40-49 1.6 50-59 1.6 60 + 2.4 Race Caucasian 0.0 AA 1.1 Hispanic -0.8 Other 1.0 GFR final < 50 1.6 GFR final > 50 0.0 Hx DM 1.1 Hx Rx HTN 1.2 >4.2 Points.=>80% bilateral discard

  18. Prediction models with Donor and Biopsy Parameters ODDS RATIOS. HxRxHTN .39 Creat.Final .53 Age .96 % GlomScl 3+ .12 Art. Hyalinosis 4+ .07 .35 .51 .96 .08 .05

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

  20. Marginal Kidneys - Patient and Graft Survival

  21. Graft Survival for ”Paired to Discard” Kidneys Recipient Characteristics (N=25*) Gender: M-18 F-7 Age: 53+ 9.8 (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 - 1.7+.4 *25/43 with complete data

  22. summary • The KidneyDiscard 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.

  23. 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.

  24. Chicago

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