FORECASTING ONE-YEAR RENAL ALLOGRAFT FUNCTION AND

SURVIVAL Yuriy Yushkov1, Nikolina Icitovic1, Ruslan Fedkiv1, and

Michael J. Goldstein1,2 (1)New York Organ Donor Network, New York, NY,

(2) Mount Sinai Medical Center, New York, NY.

ISODP 2011 Buenos Aires, Argentina

Material and Method• Aim: To identify donor and renal allograft parameters that can be utilized in

predicting renal transplant one-year graft function and survival• Method: we performed retrospective analysis of renal allograft outcomes

of1176 deceased donor kidneys. All kidneys were transplanted in the NYODN Donor Service Area.

• Allografts were evaluated using machine measured renal resistance (MMRR) and optimized needle renal biopsy technique.

• Allografts were divided into three groups by MMRR (<0.2, 0.2-0.3, >0.3).• Donor age, gender, race, type (SCD/ECD/DCD), eGFR (MDRD), renal biopsy

(glomerulosclerosis (GS), tubular interstitial scarring (TIS), vascular fibrous narrowing (VN), as well as MMRR were correlated with one-year graft function and survival.

• Kaplan-Meier curves, Log-rank tests were used to investigate the relationship between MMRR at 1.5, 3 and 5 hours (<0.2, 0.2-0.3, >0.3) and one-year graft function and survival.

• For 954 allografts multifactorial Cox regression analysis was used to reveal the relationship among donor characteristics, biopsy parameters and MMRR at 1.5, 3 and 5 hours (<0.2, 0.2-0.3, >0.3).

DONOR CHARACTERISTICS

91

451637

Donor Type

DCD

ECD

SCD

Graft Status up to 1 year Freq. %

Functioning 1086 92.35%

Failed 90 7.65%

Total 1176 100

Donor Race Frequency PercentAmer Ind/Alaska Native 3 0.26Asian 42 3.57Black 234 19.90Hispanic 231 19.64Multiracial 12 1.02White 654 55.61

Correlation amongone year graft survival, age,

gender and race

White

Non-White

Log-rank test for equality of survivor functions P<0.00

0.8

00

.85

0.9

00

.95

1.0

0

0 90 180 270 360analysis time

K-M 1-Year Survival Estimate for White/Non-White

35 yrs

50 yrs

60 yrs

75 yrs

Cox PH Regression P=0.01.8.8

5.9

.95

1S

urv

iva

l

0 90 180 270 360analysis time

1-Year Survival Estimate for Donor Age

Male

Female

Log-rank test for equality of surival functions P=0.2867

0.80

0.85

0.90

0.95

1.00

0 90 180 270 360analysis time

K-M 1-Year Survival Estimate for Gender

The absence of correlation between donors’ e-GFR

(MDRD) and MMRR

<30

30-60>60

Log-rank test for equality of survivor functions P=0.77

0.8

00

.85

0.9

00

.95

1.0

0

0 90 180 270 360analysis time

K-M 1-Year Survival Estimate for GFR

e-GFR p= 0.372

Resistance @3 hrs <30 30-60 >60 Total<0.2 70 150 245 465  15.05 32.26 52.69 100  44.87 46.44 52.46 49.15

0.2-0.3 62 126 164 352  17.61 35.8 46.59 100  39.74 39.01 35.12 37.21

>0.3 24 47 58 129  18.6 36.43 44.96 100  15.38 14.55 12.42 13.64

Correlation between MMRR at 3 hours and one-year renal allograft survival

Correlation between MMRR at 5 hours and one-year renal allograft survival

Correlation between MMRR and one year graft eGFR (MDRD)

Box Plot comparing MMRR at 3 hours and 1 year graft functionOverall p-value < 0.0001

0 < resistance <= 0.2 0.2 < resistance <= 0.3 resistance > 0.3

0

25

50

75

100

125

Rec

ipie

nt e

GF

R a

t 1

yea

r

Resistance at 3 hours

Correlation between MMRR and three year graft

eGFR (MDRD)

Recipient eGFR at 3 year

1: < 0.2 2: 0.2-0.3 3: > 0.3

0

25

50

75

100

125

150

Rec

ipie

nt e

GF

R a

t 3

year

Resistance at 3 hours

P<0.0001

.1.2

.3.4

.5P

redi

cte

d P

rob

abili

ty

<=10% 10-25% 26-50%Scarring

<0.2 0.2-0.3 >0.3Resistance at 3 hrs

Predicted Probabilities for Resistance at 3 hrs vs. Scarring(%)

P=0.002

P=0.160.1

.2.3

.4.5

Pre

dict

ed P

roba

bilit

y

<=10% 10-25% 26-50%Vasc. Narr.

<0.2 0.2-0.3 >0.3Resistance at 3 hrs

Predicted Probabilities for Resistance at 3 hrs vs. Vasc. Narrowing(%)

Correlation amongpredicted probabilities of higher MMRR and GS, TIS and Vascular Narrowing

.1.2

.3.4

.5P

redi

cte

d P

rob

abili

ty

0 10 20 30 40 50 60 70 80 90 100Glomerulosclerosis (%)

<0.2 0.2-0.3 >0.3Resistance at 3 hrs

Predicted Probabilities for Resistance at 3 hrs vs. Glomerulosclerosis(%)

P=0.035

P=0.087P=0.015

High MMRR for TIS Odds Ratio:TIS 11-25%: 1.23 TIS 26-50%:4.06

High MMRR for VN Odds Ratio:IVN 11-25%: 1.25 IVN 26-50%:1.67

High MMRR for GSOdds Ratio 1.02

Conclusion

1. MMRR together with renal allograft biopsy should be utilized to evaluate the quality of a donated kidney.

2. MMRR can be used to predict the probability of a one-year, two and three year of renal graft function and graft failure.

3. Renal pathology parameters such as GS and TIS showed a linear relationship with MMRR.

THANK YOU! Questions?

KIDNEY ASSESSMENT TOOLS

• Donor clinical assessment and lab data• Allograft Renal Biopsy performed using Optimized

Needle Biopsy Technique (ONBT) (1,2) • Biopsy frozen section evaluation performed by a single

Transplant Pathology Lab 24h/7days a week1. Total number of glomeruli/number of obsolete glomeruli2. Tubular interstitial scarring (%)3. Intimal fibrous narrowing of arteries (%)4. Presence of ATN, inflammation

• Machine preservation

1. Renal resistance/flow value (at 1,5 h, 3h, 5h)1. An Approach to Needle Biopsy Technique to Improve Glomerulus Yield. Y. Yushkov, F.W. Selck, and the Kidney–Pancreas Committee of the New York Organ Donor Network, Transplantation Proceedings, 40, 1051–1053 (2008)

2. Optimized Technique in Needle Biopsy Shown to Be of Greater Sensitivity and Accuracy Compared to the Wedge Biopsy. Y. Yushkov, S. Dikman, J. Alvarez-Casas et al . Transplantation Proceedings, 42, 2493-2497 (2010)

An Approach to Needle Biopsy Technique to Improve Glomerulus Yield. Y. Yushkov, F.W. Selck, and the Kidney–Pancreas Committee of the New York Organ Donor Network, Transplantation Proceedings, 40, 1051–1053 (2008)

Mann-Whitney test: ONBT results reported significantly more tubular interstitial scarring, intimal fibrous narrowing, (p<0.001, p<0.001).

BIOPSY TECHNIQUE

Correlation between MMRR and allograft survival

RES. 5h TOTAL FAILED Censored Censored%

<0.2 528 42 486 92.05

0.2-0.3 384 41 343 89.66

>0.3 115 19 96 83.48

TOTAL 1027 102 925 90.07

RES. 3h TOTAL FAILED Censored Censored%

<0.2 522 42 480 91.95

0.2-0.3 406 42 364 89.66

>0.3 148 23 125 84.46

TOTAL 1076 107 969 90.06