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 1990-1991 1998-1999 % Increase(%) (%)

> 65 210 (2.4) 1,019 (8.8) 385%

50-64 1,294 (14.3) 2,468 (21.2) 91%

11-49 6,535 (72.3) 7,234 (62.1) 10.7%

< 10 996 (11.0) 924 (7.9) 7.2%

Total 9,035 (100%) 11,645 (100%) 29%

UNOS 2000 Annual Report

Age 1990-1991 1998-1999 Increase (%) (%)

> 65 210 (2.4) 1,019 (8.8) X 4.8

50-64 1,294 (14.3) 2,468 (21.2) X 1.9

11-49 6,535 (72.3) 7,234 (62.1) X 1.1

< 10 996 (11.0) 924 (7.9) X 0.9

Total 9,035 (100%) 11,645 (100%) 29%

UNOS 2000 Annual Report

CADAVER DONOR AGECADAVER DONOR AGE

Discard Rates after Recovery of Cadaveric Kidneys

11%

12% 12% 12%

14%

15%

10%

11%

12%

13%

14%

15%

1995 1996 1997 1998 1999 2000*

* Data through November 30,2000SRTR

Donor Traits Associated with Kidney Graft Failure*

0

1

2

3

4

5

6

0 - 9.9 10 - 39.9 40 - 49.9 50 - 59.9 60 - 69.9 > 70

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 censoredSRTR

Survival Benefit from Marginal Kidneys

0.00

0.50

1.00

1.50

2.00

2.50

3.00

3.50

4.00

0 100 200 300 400 500 600 700

Marginal donor kidney (MDK) recipient

Ideal donor kidney (IDK) recipient

ER ER

ESES

Wait-listed dialysis patient

Days since transplantation (Equal time from wait-listing)

Relative Risk (RR) of Death

Compared to WLD IDK MDK

Time to Equal Risk (ER) 122d 185dTime to Equal Survival (ES) 256d 531d

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 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.

ROBI Kidney Biopsy PolicyROBI Kidney Biopsy Policy

BilateralBilateral

* Age >50 years* Age >50 years

* Hypertension : African American Donors* Hypertension : African American Donors

Any donor with > 5 years history Any donor with > 5 years history

* Admit S * Admit S creatinine creatinine > 1.6> 1.6

* Discrepancy in kidney size (> 2.5cm)* Discrepancy in kidney size (> 2.5cm)

* Moderate to severe aortic/arterial sclerosis* Moderate to severe aortic/arterial sclerosis

Unilateral or Affected Kidney OnlyUnilateral or Affected Kidney Only

* Acute or chronic systemic condition - ? Renal involvement* Acute or chronic systemic condition - ? Renal involvement DM, Lupus, SCD, DIC with S. DM, Lupus, SCD, DIC with S. creatinine creatinine >1.5 >1.5* Multiple cysts (>5)* Multiple cysts (>5)* Any suspicious mass or lesion* Any suspicious mass or lesion

DISCARD RATES OF BIOPSIED KIDNEYS

539 DONORS (D) – 957 KIDNEYS (K)DISCARDS - 332 K (34%)

BILATERAL BIOPSIES

418 D– 836 KDISCARDS – 305 K (36%)

UNILATERAL BIOPSIES

121 D – 121KDISCARDS – 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%)

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

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

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 USING @804 BIOPSIESMedian (25th, 75th percentiles )

FrozenPermanent

# 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%

Donor Factors as Predictors of Kidney Discard

Univariate Analysis for “all or some” kidneys transplanted

Significant p<.05 Not Significant

Age HeightRace Weight

Hx. HTN Donor DateHx.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

Predictive Model For 2/2 KIDNEY USE (227/361)

Age Points Under 40 1.5 40-49 1.5 50-59 1.3 60 + 0.0Race Caucasian 0.0 AA -1.1 Hispanic 0.2 Other -1.8GFR final < 50 0.0GFR final > 50 1.4Hx. DM 0.0No Hx HTN 1.6O-Tr Prot 0.6O-Mild A.Plaque. 0.7

4.2 pts=80% use and 5.6 pts>90% use

AUC = 0.831

Predictive Model For 2/2 KIDNEY DISCARD (91/361)

Variable PointsAge 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 1.0GFR final < 50 1.6GFR final > 50 0.0 Hx DM 1.1Hx Rx HTN 1.2

>4.2 Points.=>80% bilateral discard

False Positive Rate(1-Specificity)

Tru

e P

osi

tive

Ra

te(S

en

sitiv

ity)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

some ~ hxtxhtn + crfcsq + agecsq + fpctscl3 + faolhyl4

Area Under the Curve (AUC) = 0.81

False Positive Rate(1-Specificity)

Tru

e P

osi

tive

Ra

te(S

en

sitiv

ity)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

allused ~ hxtxhtn + crfcsq + agecsq + fpctscl3 + faolhyl4

Area Under the Curve (AUC) = 0.819

Prediction models with Donor and Biopsy Parameters

HxRxHTN .39Creat.Final .53Age .96% GlomScl 3+ .12Art. Hyalinosis 4+ .07

.35

.51

.96

.08

.05

ODDS RATIOS.

False Positive Rate(1-Specificity)

Tru

e P

osi

tive

Ra

te(S

en

sitiv

ity)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

allused ~ s(fpctscl) + s(faolhyl2) + s(age) + s(crfinal) + hxtxhtn

Area Under the Curve (AUC) = 0.891

False Positive Rate(1-Specificity)

Tru

e P

osi

tive

Ra

te(S

en

sitiv

ity)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

some ~ s(fpctscl) + s(faolhyl2) + s(age) + s(crfinal) + hxtxhtn

Area Under the Curve (AUC) = 0.876

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

Graft survival for

"paired-to-discard" kidneys

Follow-up time in months

60483624120

Cum

ulat

ive

Surv

ival

1.0

.9

.8

.7

.6

.5

.4

.3

.2

.1

0.0

Survival Function

Censored

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

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.

•