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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.
•